Effects of Early Enteral to Parenteral Protein Ratios on Brain Volume and Somatic Growth in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate whether a higher proportion of enteral vs parenteral protein ratio (E:P ratio) in the first 28 days after birth is associated with increased brain volume and somatic growth in very low birth weight (VLBW; birth weight <1500 g) infants. STUDY DESIGN: This was a retrospective analysis of a subcohort of VLBW infants (n = 256, gestational age mean 28.07 [SD 2.17] weeks, birth weight 1038.80 [SD 262.95] grams) from the Cincinnati Infant Neurodevelopment Early Prediction Study, a regional prospective study of infants born at ≤32 weeks' gestation. Brain magnetic resonance imaging was obtained at term-equivalent age. Macronutrient intake and growth metrics for the first 28 days were collected retrospectively. The primary outcome was total brain tissue volume. The relationships between E:P ratio, total and regional brain tissue volumes, and somatic growth were analyzed by multivariable linear regression models; composite variables were used to adjust for potential confounders including pregnancy risk factors and initial severity of illness. RESULTS: Higher E:P ratio was associated with increased total brain tissue volume but was not associated with change in head circumference z score. In secondary analyses, higher E:P ratio was associated with increased weight velocity. There were no significant associations between E:P ratio and change in weight or length z scores or regional brain volumes. CONCLUSIONS: Higher E:P ratio in the first 28 days was positively associated with total brain volume and weight gain. Promoting the provision of enteral over parenteral protein may improve brain and somatic growth in VLBW infants.

Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks' Gestational Age.

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Unraveling the Magnesium Connection: The Cincinnati PPG's Pioneering Work on Mineral Metabolism in Diabetes and Pregnancy.

This study aimed to review the Cincinnati PPG's contribution to the understanding and treatment of neonatal hypocalcemia (NHC) in infants of diabetic mothers. This study is a retrospective review of the NIH-funded Program Project Grant (PPG) works related to mineral metabolism in type 1 diabetic pregnant women. The PPG investigators first described the epidemiology and the additional risk factors for NHC, namely prematurity and neonatal asphyxia, but also recognized the independent effect of maternal diabetes mellitus. They explored the link between NHC and maternal/neonatal hypomagnesemia. They finally conducted a randomized control trial of prevention of NHC by early administration of magnesium sulfate soon after birth to prevent NHC. The PPG in its various phases has allowed to reveal the important role that magnesium plays in the regulation of mineral metabolism in pregnancy and in particular the pregnancy complicated by pregestational diabetes. KEY POINTS: · Poor glycemic control during pregnancy leads to maternal magnesium deficiency.. · Maternal magnesium deficiency leads to fetal and neonatal magnesium deficiency.. · Neonatal magnesium deficiency leads to functional hypoparathyroidism and parathyroid hormone resistance..

Embryonic, Fetal, and Neonatal Complications in Infants of Diabetic Mothers: Insights from the Cincinnati Diabetes in Pregnancy Program Project Grant.

This study aimed to review how the Cincinnati Diabetes in Pregnancy Program Project Grant (PPG) contributed to the understanding and treatment of neonatal complications in infants of diabetic mothers (IDMs). This is a retrospective review of all PPG work on glycemic control at different pregnancy time points and its association with embryonic, fetal, and neonatal complications, such as congenital malformations (CMs), intrauterine growth restriction, macrosomia, hypoglycemia, respiratory distress syndrome (RDS), asphyxia, and polycythemia. We found that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal hypoglycemic episodes or insulin therapy, are independent risk factors for major CMs. A suggestive association of major CMs with maternal Magnesium deficiency was also observed. Poor glycemic control during late embryogenesis and early fetal development was associated with an increased risk of minor CMs. We described a biphasic pattern of fetal growth whereby early growth delay was followed by enhanced fetal growth associated with neonatal macrosomia. Macrosomia was associated with poorer glycemic control in the third trimester and an increased risk of birth trauma. Macrosomia was also correlated with animal-origin insulin concentrations in cord blood, demonstrating that insulin bound to antibodies can cross the placenta and may affect the fetus. We also showed that neonatal hypoglycemia was significantly associated with third-trimester glycemic control, in addition to hyperglycemia occurring during labor. With modern management and adequate prenatal care, IDMs are no longer at increased risk for RDS. Perinatal asphyxia was associated with increased proteinuria appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. Polycythemia in IDMs is prevalent and correlates with proxy measurements of fetal hypoxemia (nucleated red blood cells at delivery) and poorer glycemic control in late pregnancy. The PPG in its various phases revealed the important role of glycemic control at nearly every stage of pregnancy including labor. KEY POINTS: · Poor glycemic control during embryogenesis is a major risk factor for CMs.. · Magnesium deficiency might contribute to major malformations.. · Macrosomia is associated with poor glycemic control in the third trimester.. · Strict glycemic control reduces fetal and neonatal morbidity in pregnancies with insulin-dependent diabetes mellitus..

Preconception Counseling in Women With Diabetes: The SEARCH for Diabetes in Youth Study.

Preconception counseling is recommended for all women with diabetes starting at puberty to convey the importance of optimal diabetes management for maternal and fetal outcomes. This study included 622 female participants from the SEARCH for Diabetes in Youth study with a mean age of 22.2 years (range 14-35 years). Only 53.7% reported ever receiving preconception counseling, which was significantly lower among women seeing pediatric providers than those seeing adult or all-age providers. Older age and history of prior pregnancy were associated with increased odds of reporting having received preconception counseling. Identification of barriers to delivering preconception counseling to young females with diabetes and strategies to overcome them are needed to reduce the risk for pregnancy complications and adverse offspring health outcomes.

Association between Elevated Urine Neutrophil Gelatinase-Associated Lipocalin and Postoperative Acute Kidney Injury in Neonates.

OBJECTIVE: To examine the incidence of postoperative neonatal acute kidney injury (AKI) following general surgical procedures and to test the hypothesis that postoperative urine neutrophil gelatinase-associated lipocalin (uNGAL) concentrations predict AKI. The secondary objective was to evaluate for an association between AKI and hospital mortality. STUDY DESIGN: Prospective observational study of infants undergoing abdominal and thoracic surgical procedures in the neonatal intensive care unit from October 2018 to March 2020. The primary outcome was incidence of neonatal AKI (defined by the neonatal modified Kidney Diseases Improving Global Outcomes criteria) following each procedure to postoperative day 5. Severe AKI was defined as stage 2 or 3 AKI. Urine samples were obtained pre- and postoperatively at 6 time points to evaluate for levels of uNGAL. Secondary outcomes were in-hospital mortality and length of stay. RESULTS: Subjects (n = 141) underwent a total of 192 general surgical procedures during the study period. Neonatal AKI and severe AKI occurred following 36 (18%) and 15 (8%) procedures (n = 33 subjects). Percent change of uNGAL from 24 hours preoperatively to 24 hours postoperatively was greater in subjects with neonatal AKI (190.2% [IQR 0.0, 1666.7%] vs 0.7% [IQR -31.2%,140.2%], P = .0374). The strongest association of uNGAL and AKI occurred at 24 hours postoperatively (area under the receiver operator curves of 0.81, 95% CI 0.72, 0.89). Increased mortality risk was observed in subjects with any postoperative AKI (aOR 11.1 95% CI 2.0, 62.8, P = .0063) and severe AKI (aOR 13.8; 95% CI 3.0, 63.1, P = .0007). CONCLUSION: Elevation in uNGAL 24 hours postoperative was associated with AKI. Neonates with postoperative AKI had increased mortality.

The impact of ageing on the incidence and mortality rate of bloodstream infection: A hospital-based case-cohort study in a tertiary public hospital of Brazil.

OBJECTIVE: Over the past few decades, life expectancy in Brazil has increased from 48 years in 1950s to 76 years in 2017. The aim of this study was to investigate the impact of ageing on: (1) the frequency of hospitalisations due to bloodstream infection (BSI); (2) the incidence of hospital-acquired BSI (H-BSI); (3) the incidence of BSI caused by multidrug-resistant (MDR) agents and (4) the mortality rate of BSI in a public hospital. METHODS: A hospital-based case-cohort study was conducted between 1 December 2013 and 31 December 2015. The data were analysed using multivariable logistic regression. RESULTS: A total of 500 BSI episodes were detected, among 11,102 hospitalizations. The incidence of hospitalisations resulting from BSI was significantly higher in older than younger patients (3.7/100 vs. 2.0/100, p < 0.01). Similarly, the incidence of hospital-acquired BSI was significantly higher in older patients (2.7/100 vs. 0.9/100, p < 0.01). Klebsiella pneumoniae (15.9%), Staphylococcus aureus (14.3%), Escherichia coli (13.1%) and Acinetobacter spp. (12.1%) were the most common agents isolated. MDR agents caused 37.6% of the BSI episodes; enteric Gram-negative bacilli resistant to third- or fourth-generation cephalosporins (9.7%) and carbapenem-resistant Acinetobacter spp. (9.2%) were the most common MDR agents. The following complications were independently associated with ageing: Charlson comorbidity index (OR = 1.16; 95% CI = 1.09-1.24); BSI secondary to urinary tract infection (OR = 2.14; 95% CI = 1.29-3.55); BSI secondary to pneumonia (OR = 1.77; 95% CI = 1.07-2.93) and 30-day mortality following BSI (OR = 2.19; 95% CI = 1.43-3.36). CONCLUSIONS: These data suggest ageing has a significant impact on hospitalisations due to BSI, H-BSI incidence and mortality from BSI in older patients attending a Brazilian public hospital. Age was not significantly associated with MDR-related BSI. These results indicate that age plays an important role in the increase in morbidities and mortality resulting from BSI in Brazil and that with the increased life expectancy observed over recent decades in Brazil, the burden of BSI will be expected to continue to increase. This dynamic needs to be better understood with additional studies.

Prenatal exposure to perfluoroalkyl substances and adipocytokines: the HOME Study.

OBJECTIVE: Gestational perfluoroalkyl substances exposure has been associated with decreased birthweight. We determined if gestational perfluoroalkyl substances exposure was associated with fetal metabolic markers using data from the HOME Study, a prospective birth cohort of pregnant women and their children in Cincinnati, Ohio. METHODS: Maternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid, and perfluorohexane sulfonic acid were quantified. We measured neonatal adipocytokine (leptin and adiponectin) concentrations in umbilical cord serum, and estimated percent differences with a 2-fold increase in maternal perfluoroalkyl substances concentrations among 230 mother-infant pairs. RESULTS: Median maternal serum PFOA and PFOS concentrations were 5.6 ng/mL and 14 ng/mL, respectively. Leptin was positively correlated with infant birthweight (p < 0.001). There were no statistically significant associations between maternal perfluoroalkyl substances and neonatal adipocytokine concentrations; each 2-fold increase in PFOA was associated with a non-significant increase in leptin (5%; 95% CI: -10, 22) and adiponectin (7%; 95% CI: -4, 19). CONCLUSION: Despite known associations with reduced birthweight, gestational serum perfluoroalkyl substances concentrations were not associated with neonatal adipocytokine concentrations. Further exploration of pathways of perfluoroalkyl substances associated changes in birthweight may help identify biomarkers that could be used to identify at-risk populations and develop interventions.

Variability and predictors of serum perfluoroalkyl substance concentrations during pregnancy and early childhood.

Exposure to poly- and perfluoroalkyl substances (PFAS), ubiquitous and persistent environmental contaminants, could be associated with adverse health outcomes, but there are limited longitudinal data assessing patterns and predictors of exposure during childhood. We quantified concentrations of eight different PFAS in sera collected from women during pregnancy and children at delivery and ages 3 and 8 years in 367 mother-child pairs enrolled in a prospective cohort from 2003 to 2006. In general, median childhood PFAS concentrations increased from birth to age 3 and then decreased by age 8. Maternal serum PFAS concentrations during pregnancy were strongly correlated with cord serum concentrations (0.76 < r < 0.94), but were weakly correlated with childhood concentrations (0.12 < r < 0.30). Several sociodemographic factors were associated with maternal PFAS concentrations, including income, race, and parity. In children, serum PFAS concentrations were associated with maternal age at delivery, race, parity, and child age. Breastfeeding duration was positively associated with childhood PFAS concentrations at ages 3 and 8 years. In addition, stain repellant use was associated with higher perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations at age 8 years. Serum PFAS concentrations are higher during early childhood, a potentially sensitive period of development, and were highest among breastfed children.

Possible risk for cancer among children born following assisted reproductive technology in Israel.

BACKGROUND: Among children conceived by assisted reproductive technology (ART), increased risk of adverse birth outcomes has been observed, including multiple births, preterm births, and congenital malformations. Regarding cancer among ART-conceived children, findings are discrepant. METHODS: This is a historical cohort of 9,042 ART-conceived children and 211,763 spontaneously conceived (SC) children born from 1997 through 2004. The median duration of follow-up was 10.6 years (interquartile range 9.0-12.3) in the ART group and 9.3 years (interquartile range 8.0-10.6) in the SC group. The cohort database was linked with the Israel National Cancer Registry updated until December 31, 2011 using each child's personal identification number. RESULTS: Twenty-one cases of cancer were identified in the ART group (2.2 per 10,000 person-years), as compared to 361 cancer cases in the SC group (1.8 per 10,000 person-years). The relative risk (RR) for overall cancer in the ART group compared to the SC group adjusted for maternal characteristics was 1.18 (95% confidence interval [CI] 0.80-1.75). ART children had a significantly increased risk for specific cancers, although based on small number of cases, including two cases of retinoblastoma (RR 6.18, 95% CI 1.22-31.2), as well as four cases of renal tumors (RR 3.25, 95% CI 1.67-6.32). CONCLUSION: A statistically significant increased risk for two pediatric cancers was found. However, for overall types of cancer the risk estimate was elevated but not statistically significant. Further studies with larger sample size and longer follow-up time are warranted in order to either confirm or refute these findings.

Effect of Modifiable Risk Factors on Preterm Birth: A Population Based-Cohort.

Objectives The purpose of this study is to evaluate the prevalence, impact, and interaction of short interpregnancy interval (IPI), pre-pregnancy body mass index (BMI) category, and pregnancy weight gain (PWG) on the rate of preterm birth. Methods This is a population-based retrospective cohort study using vital statistics birth records from 2006 to 2011 in OH, US, analyzing singleton live births to multiparous mothers with recorded IPI (n = 393,441). Preterm birth rate at <37 weeks gestational age was compared between the referent pregnancy (defined as normal pre-pregnancy maternal BMI, IPI of 12-24 months, and Institute of Medicine (IOM) recommended PWG) and those with short or long IPI, abnormal BMI (underweight, overweight, and obese), and high or low PWG (under or exceeding IOM recommendations). Results Only 6 % of the women in this study had a referent pregnancy, with a preterm birth rate of 7.6 % for this group. Short IPIs of <6 and 6-12 months were associated with increased rates of preterm birth rate to 12.9 and 10.4 %, respectively. Low PWG compared to IOM recommendations for pre-pregnancy BMI class was also associated with increased preterm birth rate of 13.2 % for all BMI classes combined. However, the highest rate of preterm birth of 25.2 % occurred in underweight women with short IPI and inadequate weight gain with adjOR 3.44 (95 % CI 2.80, 4.23). The fraction of preterm births observed in this cohort that can be attributed to short IPIs is 5.9 %, long IPIs is 8.3 %, inadequate PWG is 7.5 %, and low pre-pregnancy BMI is 2.2 %. Conclusions Our analysis indicates that a significant proportion of preterm births in Ohio are associated with potentially modifiable risk factors. These data suggest public health initiatives focused on preterm birth prevention could include counseling and interventions to optimize preconception health and prenatal nutrition.

Association of Bisphenol A exposure and Attention-Deficit/Hyperactivity Disorder in a national sample of U.S. children.

BACKGROUND: Bisphenol A (BPA) has been linked to changes in the dopamine system and development of an Attention-Deficit/Hyperactivity Disorder (ADHD) phenotype in animal models, with differing effects in males compared to females. We examined the association between urinary BPA concentrations and ADHD in a national sample of U.S. children, and whether this association differs by child sex. METHODS: We used data from the 2003-2004 National Health and Nutrition Examination Survey, a cross-sectional, nationally representative sample of the U.S. POPULATION: Participants were 8-15 years of age (N=460). Using a diagnostic interview to ascertain the presence of ADHD in the past year, multivariable logistic regression examined the link between concurrent urinary BPA concentrations and ADHD status. RESULTS: Of the 460 participants, 7.1% [95% CI: 4.4-11.3] met Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) criteria for ADHD. Children who had BPA concentrations at or above the median of the sample had higher prevalence of meeting criteria for ADHD (11.2% [95% CI: 6.8-17.8]) than those with BPA concentrations below the median (2.9% [95% CI: 1.1-7.2]). Higher urinary BPA concentrations were associated with ADHD (adjusted odds ratio [aOR]: 5.68 [95% CI: 1.6-19.8] for BPA concentrations above vs. below the median). In sex-stratified analyses, these associations were stronger in boys (aOR=10.9 [95% CI: 1.4-86.0]) than in girls (aOR=2.8 [95% CI: 0.4-21.3]), although the BPA by sex interaction term was not significant (p=0.25). CONCLUSION: We found evidence that higher urinary BPA concentrations were associated with ADHD in U.S. children; these associations were stronger in boys than in girls. Considering the widespread use of BPA and growing literature on neurobehavioral effects of BPA in children, further study is warranted to determine if reducing exposure to BPA may represent an important avenue for ADHD prevention.

Endocrine Disruptors: A Potential Risk Factor for Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) has increased dramatically in the past 20 years together with the obesity epidemic. Mirroring the increase in incidence of GDM is increasing use of endocrine disrupting chemicals (EDCs). EDCs are structurally similar to endogenous hormones and interfere with synthesis, secretion, activity, or elimination of natural hormones, resulting in adverse health effects, including diabetes, obesity, developmental disorders, etc. Although the association between bisphenol A (BPA), a well-studied EDC, and type 2 diabetes has been repeatedly investigated in epidemiological and animal studies, there is a dearth of studies examining EDCs and GDM. In fact, the impact of environmental toxins on perinatal health outcomes has largely been overlooked.Recognizing this research gap, the American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and International Federation of Gynecology and Obstetrics recently joined leading scientists and clinicians in a call for action to prioritize research in the consequences of exposure to toxic environmental agents on women's health. Evidence is emerging to suggest signaling molecules and EDCs are involved in the control of microRNA (miRNA) expression in trophoblast cells. We reviewed existing scientific evidence of EDCs as a risk factor for GDM as well as the potential role of miRNA in this association.

Placental Weight in Pregnant Women with Type 1 Diabetes Mellitus: The Association with Fetal Growth.

Objective To determine the association between placental weight (PW) and large for gestational age (LGA) in women with type 1 diabetes mellitus (T1DM) and whether glycemic control modifies the association. Study Design In a retrospective analysis of a cohort of women with T1DM, poor glycemic control was defined as glycohemoglobin A1(HbA1)≥ 8.5% (≥2 standard deviations [SD] above mean), and LGA as birth weight > 90th percentile, according to gestation, race, and sex. Multivariable logistic regression was used for analysis. Stratified analyses (HbA1 < 8.5% vs. HbA1 ≥ 8.5%) assessed the role of glycemic control on association between PW and LGA. Results PW in 302 pregnancies was positively associated with LGA (first vs. fourth quartile of PW; odds ratio [OR] = 9.56; 95% confidence interval [CI]: 4.14-22.08). Association varied significantly by glycemic control in the first trimester, but not in the second and third trimesters. For women with first trimester HbA1 concentration < 8.5%, there was no statistically significant association; however, with HbA1 ≥ 8.5%, there was a strong association (OR = 13.40, 95% CI: 3.31, 54.27). Conclusion There was a significant positive association between PW and LGA in infants of women with T1DM, particularly evident in pregnancies with poor glycemic control during the first trimester, highlighting the importance of achieving good glycemic control early in gestation.

Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women from a fertility clinic.

STUDY QUESTION: Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center? SUMMARY ANSWER: Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic. WHAT IS KNOWN ALREADY: Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal. STUDY DESIGN, SIZE AND DURATION: This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis. MAIN RESULTS AND THE ROLE OF CHANCE: The specific gravity-adjusted geometric mean of BPA was 1.87 µg/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (<37 years old) had thicker endometrial thickness across increasing quartiles of urinary BPA concentrations, while older women (≥37 years old) had thinner endometrial thickness across increasing quartiles of urinary BPA concentrations. LIMITATIONS, REASONS FOR CAUTION: Limitations to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population. WIDER IMPLICATIONS OF THE FINDINGS: Data on the relation between urinary BPA concentrations and reproductive outcomes remain scarce and additional research is needed to clarify its role in human reproduction. STUDY FUNDING/COMPETING INTERESTS: This work was supported by NIH grants R01ES022955, R01ES009718 and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32DK00770316 from the National Institute of Child Health and Human Development (NICHD). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Neurobehavioral problems at age 2 years in children with prenatal opioid exposure.

OBJECTIVE: To evaluate factors associated with borderline/clinical range Child Behavior Checklist (CBCL) scores in opioid-exposed children. STUDY DESIGN: Retrospective study of 94 children with prenatal opioid exposure evaluated with the CBCL at age 2 years. RESULTS: Twenty-eight children (30%) had borderline/clinical findings on the CBCL, with 27% scoring borderline/clinical for Externalizing Problems. In the multivariable model, lower Bayley-III motor scores and discharge home with mother with safety plan were associated with borderline/clinical Externalizing Problems. Medication treatment for neonatal opioid withdrawal syndrome (NOWS) was associated with normal Externalizing Problems scores. Treatment with clonidine or phenobarbital was associated with scores in the normal range in all broadband CBCL measures. CONCLUSION: Specific factors are associated with behavioral and emotional challenges measured by borderline/clinical CBCL scores among opioid-exposed children.

The Impact of Statewide Enumerated Antibullying Laws and Local School Interventions on School Spaces, Physical Harm, and Suicide Attempts for LGBTQ Youth.

Purpose: Our goal was to evaluate the impact of enumerated antibullying laws and local interventions on school affirmation, risk of physical threat or harm, and suicide attempts for lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth. Methods: This study used cross-sectional data from three national sources that provided outcomes and potential predictors: (1) The Trevor Project National Survey 2022: based on the LGBTQ youth report, (2) Movement Advancement Project: presence of LGBTQ enumerated antibullying state laws, and (3) School Health Profiles 2020: statewide prevalence of school-level strategies to improve student wellness reported by school personnel. Bivariate and multivariable logistic regression models calculated the relative risks (RRs) for each outcome. Results: LGBTQ youth (n = 27,697) were surveyed. Youth were less likely to identify their school as nonaffirming in states with enumerated laws (RR: 0.97, confidence interval [CI]: 0.94-0.99) and in states with higher percentages of gay/straight alliances (GSAs) (RR: 0.97, 95% CI: 0.96-0.97). Youth were less likely to report a history of physical threat or harm in states with more GSAs (RR: 0.96, 95% CI: 0.95-0.97). Enumerated state laws were associated with a lower risk of suicide attempts among LGBTQ youth (RR: 0.82, 95% CI: 0.77-0.87). Universal strategies/policies not specific to LGBTQ youth did not reduce risk of physical threat/harm or suicide attempts. Conclusions: Statewide enumerated antibullying protections and the presence of a GSA were associated with a decreased risk of poor outcomes among LGBTQ youth. Longitudinal studies are needed to assess the impact of recent legislative changes.

Predictors of Direct Breastfeeding in Preterm Infants.

Objective: Rates of mother's own milk (MOM) provision in the neonatal intensive care unit (NICU) vary widely, despite acceptance as the gold standard for nutrition in preterm infants. Direct breastfeeding (DBF) supports long-term provision of MOM, but factors that support DBF in preterm infants are unknown. The purpose of this study was to identify factors that predict DBF at oral feeding initiation and at NICU discharge. Methods: This was a retrospective cohort study of preterm infants born at ≤ 32 weeks who were receiving MOM at 32 weeks corrected gestational age (cohort 1) and at discharge to home (cohort 2). The primary outcomes were rates of DBF at oral feeding initiation (cohort 1) and at hospital discharge (cohort 2). We examined bivariate associations between infant characteristics, maternal sociodemographic factors, and hospital practices (e.g., lactation visit timing and frequency) with DBF outcomes and then built logistic regression models to determine the adjusted odds ratio and 95% confidence interval ([adjusted odds ratio [aOR] [95%CI]) for independent predictors of the DBF outcomes. Results: Sixty-four percent of eligible infants initiated DBF, and 51% were DBF at discharge. Sociodemographic, NICU, and lactation support factors were associated with both outcomes. Post hoc analysis showed that similar factors also influenced lactation support provision. Conclusions: Lactation support, NICU and sociodemographic variables influence DBF initiation and DBF at discharge. Interventions that optimize efficient use of available lactation support, address bias, and provide ample opportunity for DBF practice could improve rates.

Household Health-Related Social Needs in Newborns and Infant Behavioral Functioning at 6 Months.

Importance: Dysfunctional patterns of behavior during infancy can predict the emergence of mental health disorders later in childhood. The Baby Pediatric Symptom Checklist (BPSC) can identify indicators of behavioral disorders among children aged 0 to 18 months. Understanding the association of early health-related social needs (HRSNs) with poor infant behavioral functioning can inform interventions to promote early childhood mental well-being. Objective: To examine the association between household HRSNs in the first 4 months of life and BPSC results at 6 months. Design, Setting, and Participants: This was a retrospective cohort analysis of longitudinal electronic health record data. Covariates were selected based on the biopsychosocial ecological model. Logistic regression analyses examined the association of HRSN domains and the number of HRSNs with the 6-month BPSC outcomes. Participants were recruited from 6 primary care clinics within 1 health system. Children aged 5 to 8 months who were evaluated for 6-month well-child visits between March 30, 2021, and June 30, 2022, were included in the study. Exposure: Responses to the first HRSN screening tool that a caregiver completed for infants between 0 and 4 months of age. HRSN domains were examined individually and as the number of positive HRSNs. Main Outcome and Measures: BPSC screen identified for clinical review due to 1 or more elevated subscales (inflexibility, irritability, and difficulty with routines) at 6 months. Results: A total of 1541 children (mean [SD] age, 6.1 [0.5] months; 775 female [50.3%]) were included in the study. A total of 405 children (26.3%) had a BPSC screen identified for clinical review, and 328 caregivers (21.3%) reported at least 1 HRSN. Food insecurity (174 [11.3%]) and benefits issues (169 [11.0%]) were the most frequently reported HRSN. Children in households with food insecurity had statistically significant higher odds of inflexibility (adjusted odds ratio [aOR], 1.73; 95% CI, 1.14-2.63), difficulty with routines (aOR, 1.64; 95% CI, 1.05-2.57), and irritability (aOR, 1.86; 95% CI, 1.13-3.08) than children in households without food insecurity. Children in households with benefits issues had statistically significant higher odds of difficulty with routines (aOR, 1.70; 95% CI, 1.10-2.65) and irritability (aOR, 1.70; 95% CI, 1.03-2.82). Children in households with 2 or more HRSNs had consistently higher odds of having a BPSC screen identified for clinical review (aOR, 2.16; 95% CI, 1.38-3.39) compared with children with no HRSNs. Conclusions and Relevance: Results of this cohort study suggest that household food insecurity, benefits issues, and the number of HRSNs were significantly associated with a BPSC screen identified for clinical review at 6 months of age. These findings highlight the urgency of intervening on HRSNs in the newborn period to prevent adverse infant behavioral outcomes.

Mortality and Risk Factors of Death in Patients with AmpC ß-Lactamase Producing Enterobacterales Bloodstream Infection: A Cohort Study.

Aim: ESCPM bacteria include Enterobacter spp, Serratia, Citrobacter spp, Providencia spp, and Morganella spp. These Gram-negative bacilli harbor chromosomally encoded AmpC-type ß-lactamases that cause resistance to ß-lactam antibiotics, such as penicillins, ß-lactam/ß-lactamase inhibitors, and first-, second-, and third-generation cephalosporins. Bloodstream infections caused by ESCPM group bacteria (BSI-ESCPM) are difficult to treat. Purpose: To describe 30-day mortality and analyze potential risk factors for death in patients with BSI-ESCPM. Patients and Methods: A cohort study of patients aged ≥ 18 years with BSI-ESCPM was conducted at a University Hospital in Brazil, from January 2013 and December 2018. Potential risk factors for death within 30 days of bloodstream infection BSI diagnosis were analyzed using multivariable logistic regression. Results: Among 138 patients with BSI-ESCPM, 63.0% were males, with a median age of 61 years. Of 155 BSI-ESCPM episodes, 61.3% were hospital-acquired. Primary BSI-ESCPM associated with short-term central venous catheter (37.4%) and BSI-ESCPM secondary to respiratory infection (19.4%) occurred mainly. Mostly, Enterobacter spp. (49.7%) and Serratia spp. (29.0%) were isolated. Multidrug-resistance occurred in 27.7% of BSI-ESCPM episodes, involving Enterobacter spp. (16.1%) and Serratia spp. (7.7%) mainly. The mortality was 24.5%. Developing septic shock within 72 h of BSI-ESCPM diagnosis (OR: 70.26; 95% CI: 16.69-295.77; P<0.01) was risk factor for death. Conversely, combined antibiotic therapy (OR: 0.23; 95% CI: 0.05-0.94; P:0.04), BSI-ESCPM secondary to urinary infection (OR: 0.11; 95% CI: 0.01-0.99; P:0.05), and Enterobacter spp. BSI (OR: 0.16; 95% CI: 0.05-0.56; P0<0.01) was protective factor against death. Tendency of association between inadequate antibiotic therapy and death (OR: 2.19; 95% CI: 0.51-9.42; P:0.29) was observed. Conclusion: BSI-ESCPM is severe and has serious outcomes such as sepsis-associated deaths. Combined antibiotic therapy was a protective factor against death in patients with BSI-ESCPM. There is a suggestive association between inadequate antibiotic therapy and mortality. The ESCPM group bacteria that are considered to be at moderate to high risk of clinically significant AmpC production were not associated with death.