A Retrospective Review on the Effects of Nasoalveolar Molding on Infant Weight Gain and Time to Primary Lip Repair in Unilateral and Bilateral Cleft Lip and Palate.

BACKGROUND: In patients with severe cleft deformities, nasoalveolar molding (NAM) can improve long-term lip and nasal symmetry by reducing the size of the cleft, better aligning the alveolus, lip, and nose, and making the primary lip repair more predictable. Despite the increasing number of published studies on modified NAM techniques, the effects of NAM on weight gain and time to primary lip repair remain less studied. PURPOSE: This study aims to evaluate the effect of NAM on feeding, weight gain, growth velocity, and time to primary lip repair in patients with complete unilateral and bilateral cleft lip and palate (BCLP). METHODS: A retrospective, single-institution review was conducted to identify patients with complete unilateral and BCLP treated between January 2005 and June 2020. The following outcomes were measured: age at the time of lip and palate repairs; weight, height, and BMI on the date of lip repair; and growth velocity. Crude and standardized morbidity ratio-weighted differences in outcome means and 95% confidence intervals were estimated using t tests. RESULTS: Seventy-one patients were included in the study, 30 of whom underwent NAM. On average, patients treated with preoperative NAM underwent lip repair later than patients who were not treated with NAM. They also had a greater growth velocity and BMI when compared to their non-NAM counterparts. These differences, however, were not statistically significant. CONCLUSION: This study explores the relationships between the use of NAM and preoperative weight gain, as well as time to lip repair in patients with complete unilateral and BCLP. Additional studies may be needed to better elucidate the effect of NAM on weight gain and the time required for surgical repair of the cleft lip and palate.

Central Line-Associated Bloodstream Infection Risk Factors in a Pediatric Population.

BACKGROUND: Central venous line (CVL) placement in children is often necessary for treatment and may be complicated by central line-associated bloodstream infection (CLABSI). We hypothesize that line type and clinical and demographic factors at line placement impact CLABSI rates. METHODS: This is a single-institution case-control study of pediatric patients (≤18 years old) admitted between January 1, 2015, and December 31, 2019. Case patients had a documented CLABSI. Control patients had a CVL placed during the study period and were matched by sex and age in a 2:1 ratio. Bivariate and multivariate logistic regression analysis was performed. RESULTS: We identified 78 patients with a CLABSI and 140 patients without a CLABSI. After controlling for pertinent covariates, patients undergoing tunneled or non-tunneled CVL had higher odds of CLABSI than those undergoing PICC (OR 2.51, CI 1.12-5.64 and OR 3.88, CI 1.06-14.20 respectively), and patients undergoing port placement had decreased odds of CLABSI compared to PICC (OR .05, CI 0.01-.51). There were lower odds of CLABSI when lines were placed for intravenous medications compared to those placed for solid tumor malignancy (OR .15, CI .03-.79). Race and age were not statistically significant risk factors. DISCUSSION: Central lines placed for medication administration compared to solid tumors, PICC compared to tunneled and non-tunneled central lines, and ports compared to PICC were associated with lower odds of CLABSI. Future improvement efforts should focus on PICC and port placement in appropriate patients to decrease CLABSI rates.

Gender disparities in patients with aortoiliac disease requiring open operative intervention.

OBJECTIVE: Peripheral artery disease is known to affect males and females in different proportions. Disparate surgical outcomes have been quantified after endovascular aortic aneurysm repair, arteriovenous fistula creation, and treatment of critical limb ischemia. The aim of this study is to objectively quantify the sex differences in outcomes in patients undergoing open surgical intervention for aortoiliac occlusive disease. METHODS: Patients were identified in the aortoiliac occlusive disease Vascular Quality Initiative database who underwent aorto-bifemoral bypass or aortic thromboendarterectomy as determined by Current Procedural Terminology codes between 2012 and 2019. Patients with a minimum of 1-year follow-up were included. Risk differences (RDs) by sex were calculated using a binomial regression model in 30-day and 1-year incidence of mortality and limb salvage. Additionally, incidence of surgical complications including prolonged length of stay (>10 days), reoperation, and change in renal function (>0.5 mg/dl rise from baseline), were recorded. Inverse probability weighting was used to standardize demographic and medical history characteristics. Multivariate logistic regression models were employed to conduct analyses of the before mentioned clinical outcomes, controlling for known confounders. RESULTS: Of 16,218 eligible patients from the VQI data during the study period, 6538 (40.3%) were female. The mean age, body mass index, and race were not statistically different between sexes. Although there was no statistically significant difference detected in mortality between males and females at 30 days postoperatively, females had an increased crude 1-year mortality with an RD of 0.014 (95% confidence interval, 0.01-0.02; P value < .001. Males had a higher rate of a postoperative change in renal function with an RD of -0.02 (95% confidence interval, -0.03 to -0.01; P < .001). CONCLUSIONS: Although there was no sex-based mortality difference at 30 days, there was a statistically significant increase in mortality in females after open aortoiliac intervention at 1 year based on our weighted model. Male patients are statistically significantly more likely to have a decline in renal function after their procedures when compared with females. Postoperative complications including prolonged hospital stay, reoperation, and wound disruption were similar among the sexes, as was limb preservation rates at 1 year. Further studies should focus on elucidating the underlying factors contributing to sex-based differences in clinical outcomes following aortoiliac interventions.

Cost of Pediatric Trauma: A Comparison of Non-Accidental and Accidental Trauma in Pediatric Patients.

BACKGROUND: Nonaccidental trauma (NAT) affects >100,000 children in the United States every year and is associated with significant mortality and morbidity. Little is known about the financial burden of NAT, particularly in comparison to accidental trauma (AT). We sought to compare hospital charges and outcomes between children presenting with NAT and AT. METHODS: Pediatric (<16 y) trauma hospitalizations from 2006 to 2018 were identified using the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) and Kid's Inpatient Sample (KID) databases. Hospitalizations were identified as NAT or AT based on ICD codes. Discharge weights were used to obtain national estimates and standardize them across the different sampling structures. Outcomes (hospital charges, length of stay (LOS), and mortality) were compared, and multivariate regression analyses were used to assess independent predictors of hospital charges and mortality. RESULTS: Fifty-eight Thousand Two Hundred Seventy-five pediatric hospitalizations were included with 17,954 (0.3%) categorized as NAT. Children with NAT were younger, more female, less likely to identify as White, and more under public insurance than those with AT. Hospital charges were significantly higher in patients with NAT ($27,100 versus $19,900, P < 0.0001). Mortality (4.9% versus 0.0%, P < 0.0001) and LOS (3.2 d versus 1.5 d, P < 0.0001) were significantly higher among patients with NAT. Multivariable regression analyses identified NAT as a predictor of higher hospital charges, mortality, and LOS. CONCLUSIONS: Nonaccidental trauma in pediatric patients is associated with significantly higher hospital charges, mortality, and LOS than accidental trauma. Ongoing research focused on the relative impact of known risk factors and resource utilization is needed.

Incidence of venous thromboembolism in patients with peripheral arterial disease after endovascular intervention.

OBJECTIVE: Venous thromboembolism (VTE) is a well-known postoperative complication; however, the incidence of VTE after peripheral vascular intervention (PVI) has not been well described. Despite the minimally invasive nature of these procedures, the patients undergoing PVI have significant risk factors for the development of VTE. In the present study, our objective was to describe the short-term incidence of VTE after PVI, identify differences between sexes, and examine the periprocedural antiplatelet and anticoagulation regimens. METHODS: We identified adults (age >66 years) who had undergone PVI from January 1, 2008 to September 30, 2015 from the inpatient Medicare claims data. The patients were followed for 365 days after the procedure. VTE events during follow-up were identified using the International Classification of Diseases, 9th revision, diagnosis codes. The covariate-standardized 30- and 90-day cumulative incidence of VTE events, overall and stratified by sex, were estimated using Aalen-Johansen estimators, accounting for death as a competing risk. Differences in sex between females and males were identified using Gray's test. Any antiplatelet or anticoagulant prescription fill was defined as any fill from 14 days before the endovascular intervention through the date of the VTE event. Persistence with antiplatelet and anticoagulant therapy was assessed by creating daily logs of antiplatelet and anticoagulant coverage using the dispensing dates and days of supply. Over-the-counter medications (ie, aspirin) were not evaluated. RESULTS: We identified 31,593 qualifying patients with a mean age of 76.8 ± 7.4 years. Of the 31,593 patients, 46% were male, and 12% had a history of VTE. After the procedure, deep vein thrombosis (DVT) was a commonly diagnosed complication (3.8% and 4.8% at 30 and 90 days, respectively). The cumulative incidence of pulmonary embolism was 0.9% and 1.2% at 30 and 90 days after the procedure, respectively. Throughout the 90-day postoperative period, females had had a slightly increased risk of DVT compared with males (30-day risk difference, 0.007; P < .01; 90-day risk difference, 0.008; P = .02). We found no sex-based differences in the risk of pulmonary embolism. Of the patients who had developed VTE at 90 days, 970 (55%) had had no prescription fill for an antiplatelet or anticoagulant. Assuming all the patients had been taking aspirin, only 15% of the patients who had developed VTE had been taking prescribed dual antiplatelet medication persistently after PVI. In addition, among the patients who had developed VTE at 90 days, females were less likely to have had a prescription fill for an anticoagulant. CONCLUSIONS: The findings from our study have demonstrated that the incidence of VTE after PVI is high, with an increased risk of deep vein thrombosis for females. We also found that females were less likely to have been prescribed an anticoagulant after PVI. Future studies are needed to characterize the variables associated with an increased risk of VTE after PVI and to identify strategies to increase dual antiplatelet therapy or anticoagulant prescription adherence to reduce the risk of VTE.

Increased long-term bleeding complications in females undergoing endovascular revascularization for peripheral arterial disease.

OBJECTIVE: Females with peripheral arterial disease (PAD) treated with endovascular interventions have increased limb-based procedural complications compared with males. Little is known regarding long-term bleeding risk in these patients who often require long-term antiplatelet or anticoagulation therapy. We hypothesize that females have a higher incidence of bleeding events compared with males in the year after endovascular intervention for PAD. METHODS: Adults (aged ≥65 years) who underwent endovascular revascularization for PAD between 2008 and 2015 in Medicare claims data were identified. Patients were allocated by prescribed postprocedural antithrombotic therapy, including (1) antiplatelet therapy, (2) anticoagulation therapy, (3) dual antiplatelet and anticoagulation therapy, and (4) no prescription antithrombotic therapy. Bleeding events were classified as gastrointestinal, intracranial, hematoma, airway, or other. Crude and covariate-standardized 30-, 90-, and 365-day cumulative incidence of bleeding events, overall and by sex, were estimated using Aalen-Johansen estimators accounting for death as a competing risk. Sex differences were identified using Gray's test. RESULTS: Of 31,593 eligible patients, 54% were females. Females were older (77.9 years vs 75.5 years) and tended to use antiplatelet therapy more often at 30, 90, and 365 days after the intervention. Clopidogrel was the most prescribed antiplatelet, and 32% of patients continued its use at 365 days. Anticoagulants were prescribed to 26.0% of patients at the time of the procedure, and only 8.8% continued anticoagulation at 365 days. Thirty-one percent of patients were diagnosed with a bleeding event within 1 year after the intervention. The cumulative incidence of any bleeding event during the postintervention period was higher in females compared with males with a risk difference of 3% between the sex cohorts (P < .01). Specifically, females had a higher incidence of gastrointestinal bleeding and hematoma (P < .01), but a lower incidence of airway-related bleeding at each time point as compared with males (P < .01). CONCLUSIONS: Sex disparities in bleeding complications after endovascular intervention for PAD persist in the long term. Females are more likely to be readmitted with a bleeding complication up to 1 year after the procedure. Antithrombotic therapy disproportionately increases the risk of bleeding in females. Further research is necessary to understand the mechanisms responsible for abnormal coagulopathy in females after endovascular therapy.

Exploration of parent-reported food allergy symptoms via breastmilk exposures and likelihood to develop tolerance.

BACKGROUND: Knowledge is limited about the relationship between clinical reactivity to foods through breastfeeding and long-term food allergy outcomes. We explored parent-perceived symptoms of food allergy via breastfeeding and the association with future tolerance. METHODS: Subjects identified from the Chicago Food Allergy Study (2005-2011) were categorized by parent-reported reactions to maternally ingested foods via breastfeeding (50/898 peanut-allergic, 69/620 egg-allergic, and 153/589 milk-allergic). The primary outcome was tolerance [passed oral food challenge (OFC) or consumption of previously implicated food]. Secondary outcomes included severe reactions (anaphylaxis and/or cardiovascular/respiratory symptoms) and additional concomitant food allergies. Univariate chi-square analyses were performed to assess for association between variables, followed by logistic regression models. RESULTS: Of the 50 subjects with parent-reported peanut-associated symptoms with breastfeeding, none gained tolerance. There were no significant associations between parent-reported breastfeeding symptoms and development of tolerance for egg and milk (egg: OR 0.46, 95% CI 0.21-1.01, p = 0.053; milk: OR 1.13, 95% CI 0.70-1.81, p = 0.614). All egg-allergic subjects with parent-perceived symptoms while breastfeeding also reported multiple food allergies (n = 69), but milk- and peanut-allergic subjects were not more likely to have multiple allergies (milk: OR 1.89, 95% CI 0.88-4.02, p = 0.10; peanut: OR 2.36, 95% CI 0.72-7.76, p = 0.16). There were no significant associations between parent-reported breastfeeding symptoms and subsequent reaction severity. CONCLUSIONS: A significant proportion of parents perceive symptoms of food allergy attributable to indirect breastfeeding exposures. Our exploratory analysis suggests that infants with parent-perceived clinical reactivity to peanut via breastmilk may be less likely to gain tolerance. Infants with parent-reported reactivity to egg via breastmilk exposure were more likely to report multiple food allergies. Further rigorous prospective studies are needed to clarify the true prevalence of IgE-mediated food allergy symptoms attributable to indirect breastfeeding exposures and the association with development of tolerance.

Association of food allergy and decreased lung function in children and young adults with asthma.

BACKGROUND: Food allergy (FA) appears early in the atopic march, a progression that may lead to the development of asthma. The association between FA and pulmonary function in children with and without asthma remains unknown. OBJECTIVE: To investigate the association between FA and lung function in children with and without asthma. METHODS: We enrolled 1,068 children as a part of a family-based FA cohort. We then categorized children as having FA by physician diagnosis, evidence of specific IgE, and typical symptoms within 2 hours of food ingestion. We categorized asthma by physician diagnosis. We used American Thoracic Society criteria for spirometry measurements. We assessed the effects of asthma classification and FA number on lung function using mixed-effect models. RESULTS: We enrolled 1,068 children: 417 (39%) had asthma, 402 (38%) had at least 1 FA, and 162 (15%) had 2 or more FAs. Unstratified analyses found no significant association between FA number and lung function. In children with asthma, we detected statistically significant differences in predicted forced expiratory flow at 25% to 75% between children with 2 or more FAs compared with those with none (mean [SE] ß = -7.5 [3.6]; P = .04). This effect lost significance after adjusting for aeroallergen sensitization. We detected no significant associations between FA number and predicted forced expiratory volume in 1 second, forced vital capacity, and ratio of forced expiratory volume in 1 second to forced vital capacity. CONCLUSION: Having 2 or more FAs is a potential risk factor for greater small airway airflow obstruction among children with asthma, highlighting the need for close clinical follow-up and improved intervention strategies for these patients.

Genome-wide association study of maternal genetic effects and parent-of-origin effects on food allergy.

Previous genetic studies of food allergy (FA) have mainly focused on inherited genotypic effects. The role of parental genotypic effects remains largely unexplored. Leveraging existing genome-wide association study (GWAS) data generated from the Chicago Food Allergy Study, we examined maternal genotypic and parent-of-origin (PO) effects using multinomial likelihood ratio tests in 588 complete and incomplete Caucasian FA trios. We identified 1 single nucleotide polymorphism with significant (P < 5×10) maternal effect on any FA (rs4235235), which is located in a noncoding RNA (LOC101927947) with unknown function. We also identified 3 suggestive (P < 5×10) loci with maternal genetic effects: 1 for any FA (rs976078, in a gene desert region on 13q31.1) and 2 for egg allergy (rs1343795 and rs4572450, in the ZNF652 gene, where genetic variants have been associated with atopic dermatitis). Three suggestive loci with PO effect were observed: 1 for peanut allergy (rs4896888 in the ADGB gene) and 2 for any FA in boys only (rs1036504 and rs2917750 in the IQCE gene). Findings from this family-based GWAS of FA provided some preliminary evidence on maternal genotypic or PO effects on FA. Additional family-based studies are needed to confirm our findings and gain new insight into maternal and paternal genetic contribution to FA.

Genome-wide DNA methylation associations with spontaneous preterm birth in US blacks: findings in maternal and cord blood samples.

Preterm birth (PTB) affects one in six Black babies in the United States. Epigenetics is believed to play a role in PTB; however, only a limited number of epigenetic studies of PTB have been reported, most of which have focused on cord blood DNA methylation (DNAm) and/or were conducted in white populations. Here we conducted, by far, the largest epigenome-wide DNAm analysis in 300 Black women who delivered early spontaneous preterm (sPTB, n = 150) or full-term babies (n = 150) and replicated the findings in an independent set of Black mother-newborn pairs from the Boston Birth Cohort. DNAm in maternal blood and/or cord blood was measured using the Illumina HumanMethylation450 BeadChip. We identified 45 DNAm loci in maternal blood associated with early sPTB, with a false discovery rate (FDR) <5%. Replication analyses confirmed sPTB associations for cg03915055 and cg06804705, located in the promoter regions of the CYTIP and LINC00114 genes, respectively. Both loci had comparable associations with early sPTB and early medically-indicated PTB, but attenuated associations with late sPTB. These associations could not be explained by cell composition, gestational complications, and/or nearby maternal genetic variants. Analyses in the newborns of the 110 Black women showed that cord blood methylation levels at both loci had no associations with PTB. The findings from this study underscore the role of maternal DNAm in PTB risk, and provide a set of maternal loci that may serve as biomarkers for PTB. Longitudinal studies are needed to clarify temporal relationships between maternal DNAm and PTB risk.

Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring.

BACKGROUND: To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 levels at birth and child's Autism Spectrum Disorder (ASD) risk. METHODS: This report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B12 were measured from samples taken 2-3 days after birth. RESULTS: Moderate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5). CONCLUSION: There was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in-utero on early brain development.

Prenatal exposure to fever is associated with autism spectrum disorder in the boston birth cohort.

Autism spectrum disorder (ASD) is phenotypically and etiologically heterogeneous, with evidence for genetic and environmental contributions to disease risk. Research has focused on the prenatal period as a time where environmental exposures are likely to influence risk for ASD. Epidemiological studies have shown significant associations between prenatal exposure to maternal immune activation (MIA), caused by infections and fever, and ASD. However, due to differences in study design and exposure measurements no consistent patterns have emerged revealing specific times or type of MIA exposure that are most important to ASD risk. No prior studies have examined prenatal MIA exposure and ASD risk in an under-represented minority population of African ancestry. To overcome these limitations, we estimated the association between prenatal exposure to fever and maternal infections and ASD in a prospective birth cohort of an understudied minority population in a city in the United States. No association was found between prenatal exposure to genitourinary infections or flu and the risk of ASD in a nested sample of 116 ASD cases and 988 typically developing controls in crude or adjusted analyses. Prenatal exposure to fever was associated with increased ASD risk (aOR 2.02 [1.04-3.92]) after adjustment for educational attainment, marital status, race, child sex, maternal age, birth year, gestational age, and maternal smoking. This effect may be specific to fever during the third trimester (aOR 2.70 [1.00-7.29]). Our findings provide a focus for future research efforts and ASD prevention strategies across diverse populations. Autism Res 2017, 10: 1878-1890. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We looked at whether activation of the immune system during pregnancy increases the chance a child will develop ASD. We examined 116 children with ASD and 988 children without ASD that came from a predominantly low income, urban, minority population. We found that having the flu or genitourinary tract infections during pregnancy is not related to the child being diagnosed with ASD. However, we did find children were at increased risk for ASD when their mothers had a fever during pregnancy.

Individual and Joint Effects of Early-Life Ambient Exposure and Maternal Prepregnancy Obesity on Childhood Overweight or Obesity.

BACKGROUND: Although previous studies suggest that exposure to traffic-related pollution during childhood increases the risk of childhood overweight or obesity (COWO), the role of early life exposure to fine particulate matter (aerodynamic diameter <2.5 µm; PM2.5) and its joint effect with the mother's prepregnancy body mass index (MPBMI) on COWO remain unclear. OBJECTIVES: The present study was conducted to examine the individual and joint effects of ambient PM2.5 exposures and MPBMI on the risk of COWO. METHODS: We estimated exposures to ambient PM2.5in utero and during the first 2 y of life (F2YL), using data from the U.S. Environmental Protection Agency's (EPA's) Air Quality System matched to residential address, in 1,446 mother­infant pairs who were recruited at birth from 1998 and followed up prospectively through 2012 at the Boston Medical Center in Massachusetts. We quantified the individual and joint effects of PM2.5 exposure with MPBMI on COWO, defined as the child's age- and sex-specific BMI z-score ≥85th percentile at the last well-child care visit between 2 and 9 y of age. Additivity was assessed by estimating the reduced excess risk due to interaction. RESULTS: Comparing the highest and lowest quartiles of PM2.5, the adjusted relative risks (RRs) [95% confidence intervals (CIs)] of COWO were 1.3 (95% CI: 1.1, 1.5), 1.2 (95% CI: 1.0, 1.4), 1.2 (95% CI: 1.0, 1.4), 1.3 (95% CI: 1.1, 1.6), 1.3 (95% CI: 1.1, 1.5) and 1.3 (1.1, 1.5) during preconception; the first, second, and third trimesters; the entire period of pregnancy; and F2YL, respectively. Spline regression showed a dose­response relationship between PM2.5 levels and COWO after a threshold near the median exposure (10.46 µg/m3­10.89 µg/m3). Compared with their counterparts, children of obese mothers exposed to high levels of PM2.5 had the highest risk of COWO [RR≥2.0, relative excess risk due to interaction (RERI) not significant]. CONCLUSIONS: In the present study, we observed that early life exposure to PM2.5 may play an important role in the early life origins of COWO and may increase the risk of COWO in children of mothers who were overweight or obese before pregnancy beyond the risk that can be attributed to MPBMI alone. Our findings emphasize the clinical and public health policy relevance of early life PM2.5 exposure. https://doi.org/10.1289/EHP261

Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth.

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such 'missing heritability' may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10-8; empirical PG × E=1.2 × 10-8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10-9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.

Differential effects of stress and African ancestry on preterm birth and related traits among US born and immigrant Black mothers.

Preterm birth (PTB, <37 weeks of gestation) is influenced by a wide range of environmental, genetic and psychosocial factors, and their interactions. However, the individual and joint effects of genetic factors and psychosocial stress on PTB have remained largely unexplored among U.S. born versus immigrant mothers.We studied 1121 African American women from the Boston Birth Cohort enrolled from 1998 to 2008. Regression-based analyses were performed to examine the individual and joint effects of genetic ancestry and stress (including lifetime stress [LS] and stress during pregnancy [PS]) on PTB and related traits among U.S. born and immigrant mothers.Significant associations between LS and PTB and related traits were found in the total study population and in immigrant mothers, including gestational age, birthweight, PTB, and spontaneous PTB; but no association was found in U.S. born mothers. Furthermore, significant joint associations of LS (or PS) and African ancestral proportion (AAP) on PTB were found in immigrant mothers, but not in U.S. born mothers.Although, overall, immigrant women had lower rates of PTB compared to U.S. born women, our study is one of the first to identify a subset of immigrant women could be at significantly increased risk of PTB and related outcomes if they have high AAP and are under high LS or PS. In light of the growing number of immigrant mothers in the U.S., our findings may have important clinical and public health implications.

Hygiene factors associated with childhood food allergy and asthma.

BACKGROUND: Childhood food allergy and asthma rates are increasing. The hygiene hypothesis has been proposed as an explanation for the increased incidence of allergic disease. OBJECTIVE: To describe the association of childhood food allergy and asthma with hygiene factors, such as the number of siblings, antibiotic use, infection history, pet exposure, child care exposure, and maternalchild factors. METHODS: Children ages 021 years old (N = 1359) were recruited for a cross-sectional family-based study, including children with food allergy and children without food allergy, and their siblings. We assessed the associations between childhood food allergy and asthma with hygiene factors. RESULTS: Of the 1359 children, 832 (61.2%) had food allergy, and 406 (30%) had asthma. In the adjusted analysis, the prevalence of food allergy was increased if there was a history of skin infection (prevalence ratio [RRR] 1.12 [95% confidence interval {CI}, 1.011.24]) or eczema (RRR 1.89 [95% CI, 1.702.10]). The prevalence of asthma was increased with a history of respiratory syncytial virus infection (RRR 1.60 [95% CI, 1.341.90]) or eczema (RRR 1.54 [95% CI, 1.271.86]). A greater number of siblings were associated with a decreased prevalence of food allergy (RRR 0.79 [95% CI, 0.750.84]) and asthma (RRR 0.82 [95% CI, 0.740.91]). CONCLUSION: Our findings supported the accumulating evidence of an association between skin infections and eczema with food allergy. Because these results could be subject to recall bias, additional prospective studies are needed to substantiate these findings.

Patterns of allergen sensitization and self-reported allergic disease in parents of food allergic children.

BACKGROUND: Sensitization in adults has not been extensively studied. OBJECTIVE: To investigate patterns of allergen sensitization in parents of food allergic children and to compare self-report of allergic disease with specific IgE (sIgE) measurements. METHODS: A total of 1,252 mothers and 1,225 fathers of food allergic children answered standardized questionnaires about demographics, home environment, history of atopic diseases, and food allergy. Skin prick testing and sIgE serum tests were performed to 9 foods and 5 aeroallergens. RESULTS: A total of 66.1% of parents were sensitized to either a food or aeroallergen. Mean sIgE levels were low for all foods tested. A total of 14.5% of mothers and 12.7% of fathers reported current food allergy. Only 28.4% had sensitization to their reported allergen. Fathers had significantly higher rates of sensitization to both foods and aeroallergens (P < .01) than mothers. Logistic regression evaluating predictors of self-reported food allergy revealed statistically significant positive associations in fathers with self-reported asthma, environmental allergy, and eczema. For mothers, significant positive associations were found with environmental allergy and having more than 1 food allergic child. CONCLUSION: This cohort of parents of food allergic children found higher rates of sensitization to foods and aeroallergens compared with the general population. However, food sIgE levels were low and correlated poorly with self-reported food allergy. Sex differences in sensitization to foods and aeroallergens were seen.

Food Allergy Sensitization and Presentation in Siblings of Food Allergic Children.

BACKGROUND: Many parents of food allergic children have concerns about the development of food allergies in their other children. OBJECTIVE: We sought to determine prevalence of food sensitization and clinical food allergy among siblings of food allergic children. METHODS: Two thousand eight hundred and thirty-four children were enrolled in the Chicago Family Cohort Food Allergy study. One thousand one hundred and twenty children (ages 0-21 years) with a food allergy (defined by a reported reaction history and evidence of food-specific IgE or skin prick test) and at least 1 biological sibling were included in this study. RESULTS: Among siblings of children with food allergy, 33.4% had no sensitization and no clinical symptoms to food. Fifty-three percent had a positive food serum-specific IgE or skin prick test, but no reported symptoms of food allergy. Only 13.6% of siblings were both sensitized and clinically reactive to the same food. Milk allergy was the most common allergy among siblings (5.9%), followed by egg allergy (4.4%) and peanut allergy (3.7%). CONCLUSIONS: In a large cohort of food allergic families, only a small proportion of siblings were both sensitized and clinically reactive to a food. Sensitization without reactivity was common among siblings. Testing for food allergy in siblings without a history of clinical reactivity appears to be unjustified. Screening may lead to negative consequences related to potential misdiagnosis and unnecessary avoidance of a food. More data are needed to determine the absolute risk of food allergy development in siblings of food allergic children.

Weight Gain in Infancy and Overweight or Obesity in Childhood across the Gestational Spectrum: a Prospective Birth Cohort Study.

This study aimed to investigate the optimal degree of weight gain across the gestational spectrum in 1971 children enrolled at birth and followed up to age 7 years. Weight gain in infancy was categorized into four groups based on weight gain z-scores: slow (<-0.67), on track (-0.67 to 0.67), rapid (0.67 to 1.28), and extremely rapid (>1.28). Underweight and overweight or obesity (OWO) were defined as a body mass index ≤5(th) and ≥85(th) percentile, respectively, for age and gender. In our population, OWO was far more common than underweight (39.7% vs. 3.6%). Weight gain tracked strongly from age 4 to 24 months, and was positively associated with OWO and an unfavorable pattern of metabolic biomarkers, although the degree of weight gain for the risk was different across gestational categories. Extremely rapid weight gain led to a particularly high risk of OWO among children born early term and late preterm: odds ratio: 3.3 (95% confidence interval: 1.9 to 5.5) and 3.7 (1.8 to 7.5), respectively, as compared to those with on track weight gain. Our findings suggest that monitoring and ensuring optimal weight gain across the entire gestational spectrum beginning from birth represents a first step towards primary prevention of childhood obesity.

Association Between Maternal Prepregnancy Body Mass Index and Plasma Folate Concentrations With Child Metabolic Health.

IMPORTANCE: Previous reports have linked maternal prepregnancy obesity with low folate concentrations and child overweight or obesity (OWO) in separate studies. To our knowledge, the role of maternal folate concentrations, alone or in combination with maternal OWO, in child metabolic health has not been examined in a prospective birth cohort. OBJECTIVE: To test the hypotheses that maternal folate concentrations can significantly affect child metabolic health and that sufficient maternal folate concentrations can mitigate prepregnancy obesity-induced child metabolic risk. DESIGN, SETTING, AND PARTICIPANTS: This prospective birth cohort study was conducted at the Boston Medical Center, Boston, Massachusetts. It included 1517 mother-child dyads recruited at birth from 1998 to 2012 and followed up prospectively up to 9 years from 2003 to 2014. MAIN OUTCOMES AND MEASURES: Child body mass index z score calculated according to US reference data, OWO defined as a body mass index in the 85th percentile or greater for age and sex, and metabolic biomarkers (leptin, insulin, and adiponectin). RESULTS: The mean (SD) age was 28.6 (6.5) years for mothers and 6.2 (2.4) years for the children. An L-shaped association between maternal folate concentrations and child OWO was observed: the risk for OWO was higher among those in the lowest quartile (Q1) as compared with those in Q2 through Q4, with an odds ratio of 1.45 (95% CI, 1.13-1.87). The highest risk for child OWO was found among children of obese mothers with low folate concentrations (odds ratio, 3.05; 95% CI, 1.91-4.86) compared with children of normal-weight mothers with folate concentrations in Q2 through Q4 after accounting for multiple covariables. Among children of obese mothers, their risk for OWO was associated with a 43% reduction (odds ratio, 0.57; 95% CI, 0.34-0.95) if their mothers had folate concentrations in Q2 through Q4 compared with Q1. Similar patterns were observed for child metabolic biomarkers. CONCLUSIONS AND RELEVANCE: In this urban low-income prospective birth cohort, we demonstrated an L-shaped association between maternal plasma folate concentrations and child OWO and the benefit of sufficient folate concentrations, especially among obese mothers. The threshold concentration identified in this study exceeded the clinical definition of folate deficiency, which was primarily based on the hematological effect of folate. Our findings underscore the need to establish optimal rather than minimal folate concentrations for preventing adverse metabolic outcomes in the offspring.