The relationship between attachment and posttraumatic stress in children and adolescents: A meta-analytic review.

The relationship between attachment and posttraumatic stress symptoms (PTSS) has been researched extensively within adult samples, with findings consistently demonstrating a relationship between insecure attachment and increased PTSS, and between secure attachment and decreased PTSS. To a lesser extent, such relationships have also been explored within child and adolescent samples. The evidence to date is equivocal and there have been no attempts to synthesize studies. This meta-analysis aimed to provide a quantitative synthesis of studies reporting a relationship between attachment orientation (on both developmental and social psychological measures) and PTSS within children and adolescents. A random effects model was used to pool 30 studies (N = 10,431) reporting exposure to a range of traumatic events including maltreatment and war trauma. Results demonstrate a negative correlation between secure attachment and PTSS (r = -.16) and a positive correlation between insecure attachment (r = .20), avoidant attachment (r = .20), anxious attachment (r = .32), and disorganized attachment (r = .17) and PTSS. These findings indicate a small but significant relationship between attachment and PTSS in children and adolescents. Exposure to maltreatment did not moderate the relationship between secure attachment and PTSS, though strengthened the relationship between insecure attachment and PTSS.

Changes in Visceral and Ectopic Adipose Tissue Stores Across Pregnancy and Their Relationship to Gestational Weight Gain.

BACKGROUND: Excessive gestational weight gain has been associated with increased total body fat (TBF), metabolic syndrome, and abdominal obesity. However, little is known about the relationship of gestational weight gain with changes in metabolically active visceral or ectopic (hepatic and skeletal muscle) lipid stores. OBJECTIVES: In a prospective study of 50 healthy, pregnant women, we assessed whether changes in weight were associated with changes in total, visceral, and ectopic lipid stores. METHODS: Participants (ages 19-39) were primarily White (84%). The mean preconception BMI was 25.8 kg/m2 (SD, 4.5 kg/m2; min-max, 17.1-35.9 kg/m2). Measurements were completed at visits 1 and 2 at means of 16 and 34 weeks gestation, respectively, and included TBF using BOD POD; abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using MRI; and intrahepatic lipids (IHL), intramyocellular lipids (IMCL), and extramyocellular lipids (EMCL) using magnetic resonance spectroscopy. We used paired t-tests to examine changes in adipose tissue and Pearson's correlation to examine associations of adipose tissue changes and weight changes. We also examined whether changes in adipose tissue stores differed by preconception BMI (normal, overweight, and obese), using 1-way ANOVA. RESULTS: The TBF (mean change, +3.5 kg; 95% CI: 2.4-4.6 kg), SAT (mean change, +701 cm3; 95% CI: 421-981 cm3), VAT (mean change, +275 cm3; 95% CI: 170-379 cm3), and IHL (percentage water peak; median, +0.15; IQR = -0.01 to 0.32) values increased significantly; the IMCL and EMCL values did not change. Changes varied by BMI strata, with the least increase (or, for SAT, net loss) among women with obesity. Weight change was positively correlated with changes in TBF (r = 0.83; P < 0.001), SAT (r = 0.74; P < 0.001), and VAT (r = 0.63; P < 0.001) but not significantly correlated with changes in ectopic lipids (IHL, IMCL, and EMCL; -0.14 < r < 0.26). CONCLUSIONS: Preferential deposition of adipose tissue to the viscera in pregnancy, as seen in our sample, could serve an important metabolic function; however, excessive deposition in this region could negatively affect maternal health.

The importance of nutrition in pregnancy and lactation: lifelong consequences.

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.

Counseling and Behavioral Interventions for Healthy Weight and Weight Gain in Pregnancy: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Counseling and active behavioral interventions to limit excess gestational weight gain (GWG) during pregnancy may improve health outcomes for women and infants. The 2009 National Academy of Medicine (NAM; formerly the Institute of Medicine) recommendations for healthy GWG vary according to prepregnancy weight category. Objective: To review and synthesize the evidence on benefits and harms of behavioral interventions to promote healthy weight gain during pregnancy to inform the US Preventive Services Task Force recommendation. Data Sources: Ovid MEDLINE and the Cochrane Library to March 2020, with surveillance through February 2021. Study Selection: Randomized clinical trials and nonrandomized controlled intervention studies focused on diet, exercise, and/or behavioral counseling interventions on GWG. Data Extraction and Synthesis: Independent data abstraction and study quality rating with dual review. Main Outcomes and Measures: Gestational weight-related outcomes; maternal and infant morbidity and mortality; harms. Results: Sixty-eight studies (N = 25 789) were included. Sixty-seven studies evaluated interventions during pregnancy, and 1 evaluated an intervention prior to pregnancy. GWG interventions were associated with reductions in risk of gestational diabetes (43 trials, n = 19 752; relative risk [RR], 0.87 [95% CI, 0.79 to 0.95]; absolute risk difference [ARD], -1.6%) and emergency cesarean delivery (14 trials, n = 7520; RR, 0.85 [95% CI, 0.74 to 0.96]; ARD, -2.4%). There was no significant association between GWG interventions and risk of gestational hypertension, cesarean delivery, or preeclampsia. GWG interventions were associated with decreased risk of macrosomia (25 trials, n = 13 990; RR, 0.77 [95% CI, 0.65 to 0.92]; ARD, -1.9%) and large for gestational age (26 trials, n = 13 000; RR, 0.89 [95% CI, 0.80 to 0.99]; ARD, -1.3%) but were not associated with preterm birth. Intervention participants experienced reduced weight gain across all prepregnancy weight categories (55 trials, n = 20 090; pooled mean difference, -1.02 kg [95% CI, -1.30 to -0.75]) and demonstrated lower likelihood of GWG in excess of NAM recommendations (39 trials, n = 14 271; RR, 0.83 [95% CI, 0.77 to 0.89]; ARD, -7.6%). GWG interventions were associated with reduced postpartum weight retention at 12 months (10 trials, n = 3957; mean difference, -0.63 kg [95% CI, -1.44 to -0.01]). Data on harms were limited. Conclusions and Relevance: Counseling and active behavioral interventions to limit GWG were associated with decreased risk of gestational diabetes, emergency cesarean delivery, macrosomia, and large for gestational age. GWG interventions were also associated with modest reductions in mean GWG and decreased likelihood of exceeding NAM recommendations for GWG.

Residential and nonresidential substance use treatment within Indigenous populations: a systematic review.

Examining treatment outcomes of nonresidential and residential treatment programs may suggest best practices for Indigenous communities delivering treatment services. A systematic review of peer-reviewed and gray literatures comparing treatment outcomes for Indigenous populations was completed. Three studies compared treatment outcomes and reported varying results. Reported outcomes were retention and relapse rates, cultural knowledge, and participant treatment duration. Most retrieved studies described residential treatment outcomes, but it was unclear whether this modality is the best option for Indigenous people seeking treatment. Further research describing treatment modalities, across a continuum of care, situated within culturally developed treatment frameworks is required.

Maternal Pregravid Obesity Remodels the DNA Methylation Landscape of Cord Blood Monocytes Disrupting Their Inflammatory Program.

Prepregnancy maternal obesity is associated with adverse outcomes for the offspring, including increased incidence of neonatal bacterial sepsis and necrotizing enterocolitis. We recently reported that umbilical cord blood (UCB) monocytes from babies born to obese mothers generate a reduced IL-6/TNF-α response to TLR 1/2 and 4 ligands compared to those collected from lean mothers. These observations suggest altered development of the offspring's immune system, which in turn results in dysregulated function. We therefore investigated transcriptional and epigenetic differences within UCB monocytes stratified by prepregnancy maternal body mass index. We show that UCB monocytes from babies born to obese mothers generate a dampened response to LPS stimulation compared with those born to lean mothers, at the level of secreted immune mediators and transcription. Because gene expression profiles of resting UCB monocytes from both groups were comparable, we next investigated the role of epigenetic differences. Indeed, we detected stark differences in methylation levels within promoters and regulatory regions of genes involved in TLR signaling in resting UCB monocytes. Interestingly, the DNA methylation status of resting cells was highly predictive of transcriptional changes post-LPS stimulation, suggesting that cytosine methylation is one of the dominant mechanisms driving functional inadequacy in UCB monocytes obtained from babies born to obese mothers. These data highlight a potentially critical role of maternal pregravid obesity-associated epigenetic changes in influencing the function of an offspring's monocytes at birth. These findings further our understanding of mechanisms that explain the increased risk of infection in neonates born to mothers with high prepregnancy body mass index.

The Association between Maternal Height, Body Mass Index, and Perinatal Outcomes.

OBJECTIVE: To test the hypothesis that maternal height is associated with adverse perinatal outcomes, controlling for and stratified by maternal body mass index (BMI). STUDY DESIGN: This was a retrospective cohort study of all births in California between 2007 and 2010 (n = 1,775,984). Maternal height was categorized into quintiles, with lowest quintile (≤20%) representing shorter stature and the uppermost quintile (≥80%) representing taller stature. Outcomes included gestational diabetes mellitus (GDM), preeclampsia, cesarean, preterm birth (PTB), macrosomia, and low birth weight (LBW). We calculated height/outcome associations among BMI categories, and BMI/outcome associations among height categories, using various multivariable logistic regression models. RESULTS: Taller women were less likely to have GDM, nulliparous cesarean, PTB, and LBW; these associations were similar across maternal BMI categories and persisted after multivariable adjustment. In contrast, when stratified by maternal height, the associations between maternal BMI and birth outcomes varied by specific outcomes, for example, the association between morbid obesity (compared with normal or overweight) and the risk of GDM was weaker among shorter women (adjusted odds ratio [aOR], 95% confidence interval [CI]: 3.48, 3.28-3.69) than taller women (aOR, 95% CI: 4.42, 4.19-4.66). CONCLUSION: Maternal height is strongly associated with altered perinatal risk even after accounting for variations in complications by BMI.

Impact of maternal obesity and breastfeeding intention on lactation intensity and duration.

Exclusive breastfeeding (EBF) has numerous maternal health benefits. However, EBF rates are lower in mothers with obesity. We sought to better understand whether maternal body composition measurements in early pregnancy are also predictive of lower rates of EBF. Healthy pregnant women with prepregnancy body mass index (BMI) of 17.5-51 kg/m2 underwent determination of percent body fat (% body fat) in early (12-16 weeks) and late (37 weeks) gestation. Intent and duration of EBF were determined by surveys completed at 6 weeks and 6 months postpartum (PP). Unadjusted and adjusted analyses were performed to compare EBF rates and weaning by maternal BMI and % body fat. Increasing BMI and % body fat in early pregnancy were significantly associated with lower rates of EBF among women intending EBF. Women with BMI ≥ 25 were less likely to be EBF at 6 weeks and 6 months PP compared with women of normal BMI (67 and 37% vs. 91 and 79%, P value 0.005 and 0.001, respectively). Among primiparous women intending EBF, 100% of women in the lowest two body fat quartiles in early pregnancy were EBF at 6 weeks PP compared with 66.7 and 63.6% of women in the higher quartiles (P = 0.03). Lactation cessation by 6 months PP was higher with increasing maternal BMI (P = 0.001). Maternal obesity in early gestation is associated with lower EBF rates among women intending EBF and earlier weaning. Excess adiposity in early pregnancy may impede EBF.

Maternal Body Mass Index and Regional Anaesthesia Use at Term: Prevalence and Complications.

BACKGROUND: There is an evidence gap regarding the use of regional anaesthesia (epidural, spinal, or combined epidural/spinal anaesthesia) and associated complications by maternal body mass index (BMI). We examine associations between regional anaesthesia, mode of delivery, and regional anaesthesia complications by pre-pregnancy BMI categories among term deliveries. METHODS: Retrospective cohort study of births in California, 2007-2010, utilizing linked birth certificate data and patient discharge data. Outcomes were mode of delivery (among laboured deliveries) and select regional anaesthesia complications. Multivariable Poisson regression was used to adjust for maternal characteristics. RESULTS: In women undergoing labour (i.e. laboured delivery), women with higher BMI categories were more likely to receive regional analgesia in a dose-response fashion (adjusted risk ratio [RR] 1.10, 95% confidence interval [CI] 1.10, 1.11 for primiparous women with category I obesity), and in those receiving regional anaesthesia, were less likely to deliver vaginally (e.g. RR 0.85, 95% CI 0.84, 0.85 for the same category of women). Regional anaesthesia complications displayed a complex relationship with maternal BMI, with women in intermediate obesity categories having decreased odds as compared to normal-weight women, and women in the highest BMI category having a twofold increased risk of complications (RR 2.34, 95% CI 1.37, 4.02 for primiparous women). CONCLUSION: Labouring women in higher BMI categories were more likely to receive regional anaesthesia and more likely to deliver via caesarean compared to normal weight women and women without regional anaesthesia. Rates of anaesthesia complications were highest among women in the highest BMI category.

Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model.

BACKGROUND: Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI; therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels. QUESTIONS/PURPOSES: (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? METHODS: Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/kg, subcutaneous, twice daily for 5 weeks); (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (-1.8 V for 1 hour on postoperative day [POD] 7); (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (-1.8 V for 1 hour on POD 7 and POD 21); or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. RESULTS: The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0-10 CFU/mL) when compared with CONT (median = 5.7 × 10(4), range = 4.0 × 10(3)-8.0 × 10(5) CFU/mL; difference of medians = -5.6 × 10(4); p < 0.001) and VANCO (median = 4.9 × 10(3), range = 9.0 × 10(2)-2.1 × 10(4) CFU/mL; difference of medians = -4.9 × 10(3); p < 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0-0 CFU/mL) when compared with CONT (median = 1.3 × 10(2), range = 0-9.4 × 10(2) CFU/mL; difference of medians = -1.3 × 10(2); p < 0.001) but was not different from VANCO (median = 0, range = 0-1.3 × 10(2) CFU/mL; difference of medians = 0; p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0-8.0 × 10(1) CFU/mL) and bone CFU (median = 0, range = 0-2.0 × 10(1) CFU/mL) that were not different from the VANCO + 1STIM treatment group implant CFU (median = 0, range = 0-10 CFU/mL; difference of medians = 0; p = 0.334) and bone CFU (median = 0, range = 0-0 CFU/mL; difference of medians = 0; p = 0.473). The histological analysis showed no deleterious effects on the surrounding tissue as a result of the treatments. CONCLUSIONS: Using CVCES in combination with prolonged vancomycin resulted in decreased MRSA bacterial burden, and it may be beneficial in treating biofilm-related implant infections. CLINICAL RELEVANCE: CVCES combined with clinically relevant lengths of vancomycin therapy may be a treatment option for IAI and allow for component retention in certain clinical scenarios. However, more animal research and human trials confirming the efficacy of this approach are needed before such a clinical recommendation could be made.

Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples.

BACKGROUND: Maternal obesity is one of the several key factors thought to modulate neonatal immune system development. Data from murine studies demonstrate worse outcomes in models of infection, autoimmunity, and allergic sensitization in offspring of obese dams. In humans, children born to obese mothers are at increased risk for asthma. These findings suggest a dysregulation of immune function in the children of obese mothers; however, the underlying mechanisms remain poorly understood. The aim of this study was to examine the relationship between maternal body weight and the human neonatal immune system. METHODS: Umbilical cord blood samples were collected from infants born to lean, overweight, and obese mothers. Frequency and function of major innate and adaptive immune cell populations were quantified using flow cytometry and multiplex analysis of circulating factors. RESULTS: Compared to babies born to lean mothers, babies of obese mothers had fewer eosinophils and CD4 T helper cells, reduced monocyte and dendritic cell responses to Toll-like receptor ligands, and increased plasma levels of IFN-α2 and IL-6 in cord blood. CONCLUSION: These results support the hypothesis that maternal obesity influences programming of the neonatal immune system, providing a potential link to increased incidence of chronic inflammatory diseases such as asthma and cardiovascular disease in the offspring.

Cathodic Electrical Stimulation Combined With Vancomycin Enhances Treatment of Methicillin-resistant Staphylococcus aureus Implant-associated Infections.

BACKGROUND: Effective treatments for implant-associated infections are often lacking. Cathodic voltage-controlled electrical stimulation has shown potential as a treatment of implant-associated infections of methicillin-resistant Staphylococcus aureus (MRSA). QUESTIONS/PURPOSES: The primary purpose of this study was to (1) determine if cathodic voltage-controlled electrical stimulation combined with vancomycin therapy is more effective at reducing the MRSA bacterial burden on the implant, bone, and synovial fluid in comparison to either treatment alone or no treatment controls. We also sought to (2) evaluate the histologic effects of the various treatments on the surrounding bone; and to (3) determine if the cathodic voltage-controlled electrical stimulation treatment had an effect on the mechanical properties of the titanium implant as a result of possible hydrogen embrittlement. METHODS: Thirty-two adult male Long-Evans rats (Harlan Laboratories, Indianapolis, IN, USA) with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, eight animals received a treatment of cathodic voltage-controlled electrical stimulation at -1.8 V versus Ag/AgCl for 1 hour (STIM), eight received vancomycin twice daily for 1 week (VANCO), eight received the cathodic voltage-controlled electrical stimulation and vancomycin therapy combined (STIM + VANCO), and eight served as controls with no treatment (CONT). Two weeks after initial infection, the implant, bone, and synovial fluid were collected for colony-forming unit (CFU) enumeration, qualitative histological analysis by a pathologist blinded to the treatments each animal received, and implant three-point bend testing. RESULTS: The implant-associated CFU enumerated from the STIM + VANCO (mean, 3.7 × 10(3); SD, 6.3 × 10(3)) group were less than those from the CONT (mean, 1.3 × 10(6); SD, 2.8 × 10(6); 95% confidence interval [CI] of difference, -4.3 × 10(5) to -9.9 × 10(3); p < 0.001), STIM (mean, 1.4 × 10(6); SD, 2.0 × 10(6); 95% CI of difference, -2.1 × 10(6) to -1.8 × 10(3); p = 0.002), and VANCO (mean, 5.8 x 10(4); SD, 5.7 × 10(4); 95% CI of difference, -6.4 × 10(4) to -1.7 × 10(4); p < 0.001) group. The bone-associated CFU enumerated from the STIM + VANCO group (6.3 × 10(1); SD, 1.1 × 10(2)) were less than those from the CONT (mean, 2.8 × 10(5); SD, 4.8 × 10(5); 95% CI of difference, -9.4 × 10(4) to -5.0 × 10(3); p < 0.001) and STIM (mean, 2.6 × 10(4); SD, 2.5 × 10(4); 95% CI of difference, -4.1 × 10(4) to -1.6 × 10(3); p < 0.001) groups. The VANCO group (4.3 × 10(5); SD, 6.3 × 10(2)) also had lower bone-associated CFU as compared with the CONT (mean 95% CI of difference, -9.3 × 10(4) to -4.5 × 10(3); p < 0.001) and STIM (95% CI of difference, -4.0 × 10(4) to -1.5 × 10(3); p < 0.001) groups. In comparison to the synovial fluid CFU enumerated from the CONT group (mean, 3.3 × 10(4); SD, 6.0 × 10(4)), lower synovial CFU were reported for both the STIM + VANCO group (mean, 4.6 × 10(1); SD, 1.2 × 10(2); 95% CI of difference, -4.9 × 10(3) to -3.0 × 10(2); p < 0.001) and the VANCO group (mean, 6.8 × 10(1); SD, 9.2 × 10(1); 95% CI of difference, -4.9 × 10(3) to -2.8 × 10(2); p = 0.007). The histological analysis showed no discernable deleterious effects on the surrounding tissue as a result of the treatments. No brittle fracture occurred during mechanical testing and with the numbers available, no differences in implant flexural yield strength were detected between the groups. CONCLUSIONS: In this rodent model, cathodic voltage-controlled electrical stimulation combined with vancomycin is an effective treatment for titanium implant-associated infections showing greater than 99.8% reduction in bacterial burden on the implant, surrounding bone, and synovial fluid as compared with the controls and the stimulation alone groups. CLINICAL RELEVANCE: Cathodic voltage-controlled electrical stimulation combined with vancomycin may enable successful treatment of titanium orthopaedic implant-associated infections with implant retention. Future studies will focus on optimization of the stimulation parameters for complete eradication of infection and the ability to promote beneficial host tissue responses.

The association of cord serum cytokines with neurodevelopmental outcomes.

OBJECTIVE: To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). STUDY DESIGN: Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1ß), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. RESULTS: Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1ß were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1ß, and TNF-α) were not elevated with CP or low PDI. CONCLUSION: Cord serum IL-8, IL-1ß, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.

Moraxella catarrhalis is susceptible to antimicrobial photodynamic therapy with Photofrin.

BACKGROUND AND OBJECTIVE: Moraxella catarrhalis is a significant cause of pediatric otitis media (OM), which is the most prevalent bacterial infection in children and primary reason for antibiotic administration in this population. Moreover, biofilm formation has been implicated as a primary mechanism of chronic or recurrent OM disease. As bacterial biofilms are inherently resistant to most antibiotics and these complex structures also present a significant challenge to the immune system, there is a clear need to identify novel antimicrobial approaches to treat OM infections. In this study, we evaluated the potential efficacy of antibacterial photodynamic therapy (aPDT) with porfimer sodium (Photofrin (PF)) against planktonic as well as biofilm-associated M. catarrhalis. MATERIALS AND METHODS: The bactericidal activity of aPDT with PF was assessed against multiple recent clinical isolates of M. catarrhalis grown planktonically as well as in biofilms. The bactericidal activity of PF-aPDT was quantified by enumeration of colony forming units post-treatment. The effect of aPDT on M. catarrhalis biofilms was further investigated with scanning electron microscopy (SEM) imaging. RESULTS: aPDT with PF significantly reduced M. catarrhalis viability. Although PF-aPDT caused higher killing in planktonic grown organisms (5-6 log kill), biofilm grown bacteria also demonstrated a statistically significant reduction in viable organisms (3-4 log decrease in recoverable bacteria) following treatment as compared to saline only controls (P < 0.01). SEM studies indicated the PF-aPDT treated bacteria exhibited prominent morphological changes with visibly distorted cell membranes. CONCLUSIONS: aPDT with PF elicits significant bactericidal activity against both planktonic and biofilm-associated M. catarrhalis, suggesting this technology warrants further analysis as a potential novel antimicrobial treatment for acute or recurrent OM.

The effect of maternal body mass index on perinatal outcomes in women with diabetes.

OBJECTIVE: To determine the effect of increasing maternal obesity, including superobesity (body mass index [BMI] ≥ 50 kg/m2), on perinatal outcomes in women with diabetes. STUDY DESIGN: Retrospective cohort study of birth records for all live-born nonanomalous singleton infants ≥ 37 weeks' gestation born to Missouri residents with diabetes from 2000 to 2006. Women with either pregestational or gestational diabetes were included. RESULTS: There were 14,595 births to women with diabetes meeting study criteria, including 7,082 women with a BMI > 30 kg/m2 (48.5%). Compared with normal-weight women with diabetes, increasing BMI category, especially superobesity, was associated with a significantly increased risk for preeclampsia (adjusted relative risk [aRR] 3.6, 95% confidence interval [CI] 2.5, 5.2) and macrosomia (aRR 3.0, 95% CI 1.8, 5.40). The majority of nulliparous obese women with diabetes delivered via cesarean including 50.5% of obese, 61.4% of morbidly obese, and 69.8% of superobese women. The incidence of primary elective cesarean among nulliparous women with diabetes increased significantly with increasing maternal BMI with over 33% of morbidly obese and 39% of superobese women with diabetes delivering electively by cesarean. CONCLUSION: Increasing maternal obesity in women with diabetes is significantly associated with higher risks of perinatal complications, especially cesarean delivery.

Barriers to implementing good nutrition in pregnancy and early childhood: Creating equitable national solutions.

Exposure to deleterious stressors in early life, such as poor nutrition, underlies most adult-onset chronic diseases. As rates of chronic disease continue to climb in the United States, a focus on good nutrition before and during pregnancy, lactation, and early childhood provides a potential opportunity to reverse this trend. This report provides an overview of nutrition investigations in pregnancy and early childhood and addresses racial disparities and health outcomes, current national guidelines, and barriers to achieving adequate nutrition in pregnant individuals and children. Current national policies and community interventions to improve nutrition, as well as the current state of nutrition education among healthcare professionals and students, are discussed. Major gaps in knowledge and implementation of nutrition practices during pregnancy and early childhood were identified and action goals were constructed. The action goals are intended to guide the development and implementation of critical nutritional strategies that bridge these gaps. Such goals create a national blueprint for improving the health of mothers and children by promoting long-term developmental outcomes that improve the overall health of the US population.

The K1 capsular polysaccharide from Acinetobacter baumannii is a potential therapeutic target via passive immunization.

The emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P < 0.05). Lastly, treatment with MAb 13D6 3 and 24 h after bacterial challenge in a rat soft tissue infection model resulted in a significant decrease in the growth/survival of a K1-positive strain compared to that of a K1-negative strain or to treatment with a vehicle control (P < 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.

Characterization of a trifunctional glucosyltransferase essential for Moraxella catarrhalis lipooligosaccharide assembly.

The human respiratory tract pathogen Moraxella catarrhalis expresses lipooligosaccharides (LOS), glycolipid surface moieties that are associated with enhanced colonization and virulence. Recent studies have delineated the major steps required for the biosynthesis and assembly of the M. catarrhalis LOS molecule. We previously demonstrated that the glucosyltransferase enzyme Lgt3 is responsible for the addition of at least one glucose (Glc) molecule, at the ß-(1-4) position, to the inner core of the LOS molecule. Our data further suggested a potential multifunctional role for Lgt3 in LOS biosynthesis. The studies reported here demonstrate that the Lgt3 enzyme possesses two glycosyltransferase domains (A1 and A2) similar to that of other bifunctional glycosyltransferase enzymes involved in surface polysaccharide biosynthesis in Escherichia coli, Pasteurella multocida and Streptococcus pyogenes. Each Lgt3 domain contains a conserved DXD motif, shown to be involved in the catalytic activity of other glycosyltransferases. To determine the function of each domain, A1 (N-terminal), A2 (C-terminal) and double A1A2 site-directed DAD to AAA mutants were constructed and the resulting LOS phenotypes of these modified strains were analyzed. Our studies indicate that the Lgt3 N-terminal A1 catalytic domain is responsible for the addition of the first ß-(1-3) Glc to the first Glc on the inner core. The C-terminal catalytic domain A2 then adds the ß-(1-4) Glc and the ß-(1-6) Glc, confirming the bifunctional nature of this domain. The results from these experiments demonstrate that Lgt3 is a novel, multifunctional transferase responsible for the addition of three Glcs with differing linkages onto the inner core of M. catarrhalis LOS.

Monoclonal Antibody Therapy of Breastfeeding Patient Infected with SARS-CoV-2: A Case Report.

Introduction: Although safety data demonstrated the efficacy and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination for all individuals over 6 months of age, including pregnant and breastfeeding individuals, optimal treatment courses for symptomatic pregnant and lactating individuals infected with SARS-CoV-2 remain to be defined. Case Description: A coronavirus disease 2019 (COVID-19)-vaccinated breastfeeding woman received anti-SARS-CoV-2 monoclonal antibody treatment casirivimab-imdevimab 5 days after diagnosis of a symptomatic breakthrough SARS-CoV-2 infection. Results and Conclusions: The patient did not present with obvious defects in innate or adaptive cellular subsets, but compared with controls had minimal maternal antibody response to recommended pregnancy vaccinations including SARS-CoV-2 and tetanus, diphtheria, pertussis (TDaP). The outcome of the monoclonal antibody infusion treatment was favorable as it transiently increased SARS-CoV-2 antibody titers in plasma and human milk compartments.