Prenatal antimicrobial use and early-childhood body mass index.

BACKGROUND/OBJECTIVES: Growing evidence suggests that antibiotic use is associated with childhood body mass index (BMI), potentially via mechanisms mediated by gut microbiome alterations. Less is known on the potential role of prenatal antimicrobial use in offspring obesity risk. We examined whether prenatal antibiotic or antifungal use was associated with BMI at the age of 2 years in 527 birth cohort participants. METHODS/SUBJECTS: Antimicrobial use was obtained from the prenatal medical record. Height and weight were measured at the age of 2 years. Overweight/obesity was defined as a BMI ⩾85th percentile. RESULTS: A total of 303 (57.5%) women used antibiotics and 101 (19.2%) used antifungals during pregnancy. Prenatal antifungal use was not associated with child BMI at the age of 2 years. In the fully adjusted model, prenatal antibiotic use was associated with a 0.20±0.10 (P=0.046) higher mean BMI Z-score at the age of 2 years. Associations between prenatal antibiotic use and childhood BMI varied by trimester of exposure, with first or second-trimester exposure more strongly associated with larger BMI at the age of 2 years for both BMI Z-score (interaction P=0.032) and overweight/obesity (interaction P=0.098) after covariate adjustment. CONCLUSIONS: Prenatal antibiotic, but not antifungal, use is associated with larger BMI at the age of 2 years; associations were stronger for antibiotic exposures in earlier trimesters. Future studies examining whether these associations are due to alterations in the maternal and/or infant microbiome are necessary. Children who are overweight at the age of 2 years are at higher risk for being overweight as they age; prenatal antibiotic use is a potentially modifiable exposure that could reduce childhood obesity.

Combined effects of prenatal medication use and delivery type are associated with eczema at age 2 years.

BACKGROUND: Separately, prenatal antibiotics and Caesarian delivery have been found to be associated with increased risk of allergic diseases. It is not clear whether these factors may modify the effect of each other. OBJECTIVE: To assess whether the associations between delivery types and eczema, sensitization and total IgE at age 2 years were modified by maternal use of prenatal medications. METHODS: Prenatal charts of women enrolled in the WHEALS birth cohort were reviewed for delivery mode and medications prescribed and administered throughout their entire pregnancy, including systemic antibiotics and vaginally applied antifungal medications. The associations between the delivery mode and select medications and, eczema, sensitization (≥ 1 of 10 allergen-specific IgE ≥ 0.35 IU/mL) and total IgE at age 2 years were assessed. RESULTS: There was a lower risk of eczema among vaginally vs. c-section born children (relative risk adjusted for race = aRR = 0.77, 95% CI 0.56, 1.05). Although not statistically significantly different, this association was stronger among the subset of children born vaginally to a mother who did not use systemic antibiotics or vaginal antifungal medications (aRR = 0.69, 95% CI 0.44, 1.08) compared to those born vaginally to mothers who used systemic antibiotics or vaginal antifungals (aRR = 0.81, 95% CI 0.57, 1.14). A protective association between vaginal birth and sensitization (aRR = 0.86, 95% CI 0.72, 1.03) was similar for those children born vaginally to a mother who did not (aRR = 0.87, 95% CI 0.69, 1.10) and who did (RR = 0.85, 95% CI 0.70, 1.04) use systemic antibiotics or vaginal antifungal medications. There were no associations with total IgE. CONCLUSIONS: Children born vaginally had lower risk of eczema and sensitization compared with those born via c-section; however, the protective association with eczema may be slightly weakened when mothers took systemic antibiotics or vaginally applied medications during pregnancy.

Lifetime dog and cat exposure and dog- and cat-specific sensitization at age 18 years.

BACKGROUND: Prior research about whether keeping a dog or cat at home causes allergies to that pet has been limited to outcomes in early childhood. OBJECTIVE: Evaluate the association between lifetime dog and cat exposure and allergic sensitization to the specific animal at 18 years of age. METHODS: Participants enrolled in the Detroit Childhood Allergy Study birth cohort during 1987-1989 were contacted at the age 18 years. Sensitization to dog or cat was defined as animal-specific IgE ≥ 0.35 kU/L. Annual interview data from childhood and follow-up interviews at age 18 years were used to determine lifetime indoor dog and cat exposure (indoor was defined when the animal spent >50% of their time inside the house). Exposure was considered in various ways: first year, age groups and cumulative lifetime. Analyses were conducted separately for dogs and cats. RESULTS: Among males, those with an indoor dog during the first year of life had half the risk [relative risk (RR)=0.50, 95% confidence interval (CI) 0.27, 0.92] of being sensitized to dogs at age 18 compared with those who did not have an indoor dog in the first year. This was also true for males and females born via c-section (RR=0.33, 95% CI 0.07, 0.97). Overall, teens with an indoor cat in the first year of life had a decreased risk (RR=0.52, 95% CI 0.31, 0.90) of being sensitized to cats. Neither cumulative exposure nor exposure at any other particular age was associated with either outcome. CONCLUSIONS AND CLINICAL RELEVANCE: The first year of life is the critical period during childhood when indoor exposure to dogs or cats influences sensitization to these animals.

Prenatal exposure to household pets influences fetal immunoglobulin E production.

BACKGROUND: Early life pet exposure may protect against allergic sensitization during childhood. Few studies have evaluated the effect of prenatal pet exposure on potential neonatal markers of allergic risk. OBJECTIVE: The aim of this study was to investigate whether maternal exposure to pets affects cord blood IgE levels in a population-based, general risk, ethnically mixed birth cohort. METHODS: Pet keeping during pregnancy was ascertained from women residing in a defined area of Wayne County Michigan and recruited from five staff model obstetric clinics. Maternal venous blood was analysed for total and allergen-specific IgE along with cord blood total IgE from 1049 infants. RESULTS: Compared with infants from households with no cats or dogs kept indoors during pregnancy, infants whose homes had either cats or dogs had significantly reduced mean cord IgE levels [0.34 IU/mL (95% CI 0.30-0.38) vs. 0.24 IU/mL (0.20-0.27), P=0.025]. Similar effects were apparent in cat-only households [0.21 IU/mL (0.16-0.27), P=0.020] and dog-only households [0.24 IU/mL (0.19-0.29), P=0.045]. There was no effect on results when excluding mothers who reported avoiding pets due to allergy-related concerns. CONCLUSION: Mothers with either cats or dogs in their home during pregnancy deliver children with lower cord blood IgE levels compared with mothers who do not live with these pets, supporting the hypothesis that pet exposure influences immune development in a manner that is protective for atopy and is operant even before birth.

Health service use by African Americans and Caucasians with asthma in a managed care setting.

Managed care plan members provide a population for analysis that minimizes the financial barriers to routine medical care that have been linked to high rates of asthma-related hospitalization, emergency care, and mortality among urban African Americans. We examined patterns of asthma care among 464 African American (AA) and 1,609 Caucasian (C) asthma patients, age 15 to 45 yr, in a southeast Michigan managed care system during 1993. Compared with C, AA had fewer visits to asthma specialists (0.32 versus 0.50 visits/yr, p = 0.002), and filled fewer prescriptions for inhaled steroids (1.44 versus 1.74 Rx/yr, p = 0.038), while being more likely to visit the emergency department with asthma (0.71 versus 0.28 visits/yr, p < 0. 001), to be hospitalized with asthma (0.08 versus 0.03 admissions/yr, p = 0.002), or to have filled prescriptions for oral steroids (0.91 versus 0.59 Rx/yr, p < 0.001). AA were equally likely to have visited a primary care physician for asthma (0.95 versus 0.93 visits/yr, p = 0.81). Similar physician visit profiles and discrepancies in the use of oral steroids persisted when analyzing exclusively low socioeconomic status subgroups. These results suggest that ethnic differences in patterns of asthma-related health care persist within managed care settings and are only partially due to financial barriers.

Platelet-activating factor primes human eosinophil generation of superoxide.

Platelet-activating factor (PAF) is a potent inflammatory mediator that can cause airway obstruction and hyperresponsiveness; these processes are also associated with pulmonary eosinophilia, suggesting a link between these two events. Thus, PAF's interaction with eosinophils may provide a mechanism for airway damage. However, direct in vitro activation of eosinophils by PAF requires concentrations that are likely higher than those achieved in vivo. As a result, we investigated whether lower, more physiologic concentrations of PAF could prime eosinophils for subsequent activation to another receptor-stimulated factor, in this case formylmethionylleucylphenylalanine (FMLP). To test this hypothesis, eosinophils were preincubated (1 and 15 min) with low concentrations of PAF (1 x 10(-8) and 1 x 10(-10) M); this exposure to PAF resulted in enhanced generation of superoxide anion to FMLP stimulation. Moreover, similar concentrations of PAF decreased eosinophil density and increased expression of cell surface CR3 receptors. Finally, low, nonactivating concentrations of PAF (1 x 10(-10) to 1 x 10(-8) M) caused transient increases in eosinophil cytosolic free Ca2+ concentrations. Collectively, these responses are consistent with the hypothesis that short-term exposure to low concentrations of PAF primes eosinophils to cause an enhanced inflammatory response upon subsequent activation to another receptor agonist. The consequences of this PAF-associated phenomenon can produce an enhanced inflammatory response and airway injury.

The effect of platelet-activating factor on the generation of superoxide anion in human eosinophils and neutrophils.

The precise role of platelet-activating factor (PAF) in asthma has yet to be established. Nonetheless, the potential relationship between PAF and asthma appears to include the eosinophil (EOS) as an important link. Thus, to evaluate the effect of PAF on leukocyte-dependent inflammation, purified populations of human blood EOSs and neutrophils were isolated from the same subject. The two granulocyte populations were then incubated with PAF, and superoxide anion (O2-) generation was measured by reduction of cytochrome c in a microassay system. Both granulocyte cell types generated O2- when they were incubated with PAF. However, the generation of O2- was 3.4 times greater with EOSs (9.8 +/- 1.5 nmole of cytochrome c reduced per 5 x 10(5) cells) than neutrophils (2.9 +/- 0.4 nmole of cytochrome c reduced per 5 x 10(5) cells; p less than 0.0001). When the effect of PAF on [Ca++]i was measured with the fluorescent label, Indo-1, PAF caused similar increases in cellular fluorescence in both neutrophils and EOSs, but the increase in [Ca++]i of neutrophils occurred with lower concentrations of PAF. Furthermore, when similar experiments were conducted in the presence of an extracellular calcium chelator, ethylene glycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraacetic acid, there was partial suppression in both the cellular fluorescence and O2- generation to PAF; this suggests that full expression of EOS generation of O2- by PAF requires both intracellular mobilization and a transmembrane influx of Ca++. Our data indicate that PAF can stimulate leukocyte O2- generation, but this response is greater in the EOS than the neutrophil. Therefore, our findings support the observation that the EOS is more responsive to PAF activation than other granulocytes and that this difference may contribute to participation of PAF in asthma.