scholarly journals The Fetal Antibiotic EXposure (FAX) Study: Research on the Effect of in-utero antibiotic exposure on childhood outcomes (Preprint)

2018 ◽  
Author(s):  
Corinna Koebnick ◽  
Sara Y. Tartof ◽  
Margo A. Sidell ◽  
Emily Rozema ◽  
Joanie J Chung ◽  
...  
Keyword(s):  
In Utero ◽  
Autism Spectrum ◽  
Adverse Outcomes ◽  
First Year ◽  
In Utero Exposure ◽  
Study Cohort ◽  
Antibiotic Exposure ◽  
Real World Data ◽  
First Year Of Life ◽  
Over Time

BACKGROUND The widespread use of antepartum and intrapartum antibiotics has raised concerns about the possible disruption of the child's gut microbiota, and effects on the ‘maturation’ from the infant to the adult microbiome. The Fetal Antibiotic EXposure (FAX) Study provides a cohort to examine the association between in-utero exposure to antibiotics and adverse childhood outcomes including body weight, atopic diseases, and autism spectrum disorders and to investigate the role of other potential factors mitigating or moderating the risk for adverse outcomes. OBJECTIVE To describe the methods, cohort characteristics, and retention of infants included in the study cohort. METHODS For this retrospective cohort study, we included children born in KPSC hospitals between January 1, 2007 and December 31, 2015 within 22-44 weeks of gestation with KPSC insurance coverage during the first year of life. Follow-up data collection is through electronic medical record (EMR) data from Kaiser Permanente Southern California (KPSC). RESULTS The study cohort was comprised of 223,431 children of which 65.7% were exposed to antibiotics in-utero; 19.0% were exposed during the antepartum period, 30.0% during the intrapartum period, and 16.7% exposed during both the antepartum and intrapartum periods. During their first year of life, children had a median of 5 BMI measurements; the frequency of BMI measurements declined to a median of 3 in their second year of life and 2 for 3-5 years of age. The 5-year retention of children in the health plan was over 80% with the highest retention for Hispanic children. CONCLUSIONS This cohort of children will provide a unique opportunity to address key questions regarding the long-term sequelae of in-utero exposure to antibiotics using real-world data. The high retention and multiple medical visits over time allow us to model the trajectories of BMI over time.

scholarly journals Effect of In-Utero Antibiotic Exposure on Childhood Outcomes: Methods and Baseline Data of the Fetal Antibiotic EXposure (FAX) Cohort Study

10.2196/12065 ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. e12065 ◽  
Author(s):  
Corinna Koebnick ◽  
Sara Y Tartof ◽  
Margo A Sidell ◽  
Emily Rozema ◽  
Joanie Chung ◽  
...  
Keyword(s):  
Cohort Study ◽  
Insurance Coverage ◽  
In Utero ◽  
Autism Spectrum ◽  
Adverse Outcomes ◽  
In Utero Exposure ◽  
Study Cohort ◽  
Antibiotic Exposure ◽  
Real World Data ◽  
Over Time

Background The widespread use of antepartum and intrapartum antibiotics has raised concerns about the possible disruption of the child’s gut microbiota and effects on the maturation from the infant to the adult microbiome. The Fetal Antibiotic EXposure (FAX) study provides a cohort to examine the association between in-utero exposure to antibiotics and adverse childhood outcomes including body weight, atopic diseases, and autism spectrum disorders and to investigate the role of other potential factors mitigating or moderating the risk for adverse outcomes. Objective The aim of this paper was to describe the methods, cohort characteristics, and retention of infants included in the study cohort. Methods For this retrospective cohort study, we included children born in Kaiser Permanente Southern California (KPSC) hospitals between January 1, 2007, and December 31, 2015, within 22 to 44 completed weeks of gestation with KPSC insurance coverage during the first year of life. Follow-up data collection was performed through electronic medical records. Results The study cohort was comprised 223,431 children of which 65.7% (146,720/223,431) were exposed to antibiotics in-utero: 19.0% (42,511/223,431) were exposed during the antepartum period, 30.0% (66,896/223,431) during the intrapartum period, and 16.7% (37,313/223,431) exposed during both the antepartum and intrapartum periods. Conclusions This cohort of children will provide a unique opportunity to address key questions regarding the long-term sequelae of in-utero exposure to antibiotics using real-world data. The high retention and multiple medical visits over time allow us to model the trajectories of body mass index over time. International Registered Report Identifier (IRRID) DERR1-10.2196/12065

Risk of infections during the first year of life after in utero exposure to drugs acting on immunity: A population-based cohort study

2016 ◽  
Vol 113 ◽  
pp. 557-562 ◽  
Author(s):  
Lucie Palosse-Cantaloube ◽  
Caroline Hurault-Delarue ◽  
Anna-Belle Beau ◽  
Jean-Louis Montastruc ◽  
Isabelle Lacroix ◽  
...  
Keyword(s):  
Cohort Study ◽  
Population Based ◽  
In Utero ◽  
First Year ◽  
In Utero Exposure ◽  
First Year Of Life

In utero exposure to antiepileptic drugs is associated with learning disabilities among offspring

2018 ◽  
Vol 89 (12) ◽  
pp. 1324-1331 ◽  
Author(s):  
Laura Fuglsang Bech ◽  
Christoffer Polcwiartek ◽  
Kristian Kragholm ◽  
Mikkel Porsborg Andersen ◽  
Christopher Rohde ◽  
...  
Keyword(s):  
Learning Disabilities ◽  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
Developmental Disorders ◽  
Compulsory Education ◽  
In Utero ◽  
Autism Spectrum ◽  
First Year ◽  
In Utero Exposure ◽  
Adjusted Risk

ObjectivesIn utero exposure to antiepileptic drugs has previously been associated with adverse outcome among offspring, but evidence on longer term milestone development remains limited. We investigated the association between in utero exposure to antiepileptic drugs and learning disabilities in the first year of compulsory education among offspring and assessed which antiepileptic drugs carried the highest risk.MethodsThis population-based case–cohort study used Danish nationwide register data from 2005 to 2008. Cases were offspring exposed to antiepileptic drugs in utero, and controls were unexposed offspring of mothers previously redeeming antiepileptic drug prescriptions. Offspring were followed from birth until the first year of compulsory education from 2011 to 2015. Learning disabilities were defined as mental retardation, specific developmental disorders, autism spectrum disorders, emotional/behavioural disorders or having special educational needs. Logistic regression was used to compute ORs with 95% CIs adjusted for potential confounding.ResultsOf 117 475 incident singleton births, 636 cases and 434 controls were included (median age: 6.1 years, males: 55.7%). Learning disabilities were identified among 7.1% cases compared with 3.7% for controls. During any trimester, the adjusted OR of the association between in utero exposure to antiepileptic drugs and learning disabilities was 2.20 (95% CI 1.16 to 4.17). Among cases not exposed to polytherapy (n=556), in utero exposure to lamotrigine compared with another antiepileptic drug was associated with the lowest adjusted risk (OR 0.42, 95% CI 0.19 to 0.92), and valproate carried a higher risk (OR 4.67, 95% CI 1.73 to 12.59).ConclusionIn utero exposure to antiepileptic drugs was significantly associated with learning disabilities among offspring. Lamotrigine should preferentially be considered over, for example, valproate if clinically feasible.

scholarly journals The natural history of Canavan disease: 23 new cases and comparison with patients from literature

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Annette Bley ◽  
Jonas Denecke ◽  
Alfried Kohlschütter ◽  
Gerhard Schön ◽  
Sandra Hischke ◽  
...  
Keyword(s):  
Severity Score ◽  
Canavan Disease ◽  
Psychomotor Development ◽  
Rank Test ◽  
First Year ◽  
Study Cohort ◽  
Pooled Data ◽  
Kaplan Meier ◽  
History Of ◽  
First Year Of Life

Abstract Background Canavan disease (CD, MIM # 271900) is a rare and devastating leukodystrophy of early childhood. To identify clinical features that could serve as endpoints for treatment trials, the clinical course of CD was studied retrospectively and prospectively in 23 CD patients. Results were compared with data of CD patients reported in three prior large series. Kaplan Meier survival analysis including log rank test was performed for pooled data of 82 CD patients (study cohort and literature patients). Results Onset of symptoms was between 0 and 6 months. Psychomotor development of patients was limited to abilities that are usually gained within the first year of life. Macrocephaly became apparent between 4 and 18 months of age. Seizure frequency was highest towards the end of the first decade. Ethnic background was more diverse than in studies previously reported. A CD severity score with assessment of 11 symptoms and abilities was developed. Conclusions Early hallmarks of CD are severe psychomotor disability and macrocephaly that develop within the first 18 months of life. While rare in the first year of life, seizures increase in frequency over time in most patients. CD occurs more frequently outside Ashkenazi Jewish communities than previously reported. Concordance of phenotypes between siblings but not patients with identical ASPA mutations suggest the influence of yet unknown modifiers. A CD severity score may allow for assessment of CD disease severity both retrospectively and prospectively.

scholarly journals Early Infant Feeding Practices as Possible Risk Factors for Immunoglobulin E-Mediated Food Allergies in Kuwait

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Dalal Alkazemi ◽  
Munirah Albeajan ◽  
Stan Kubow
Keyword(s):  
Risk Factors ◽  
Vitamin D ◽  
Immunoglobulin E ◽  
Food Allergies ◽  
First Year ◽  
Antibiotic Exposure ◽  
Pediatric Allergy ◽  
Potential Risk Factors ◽  
Ige Mediated ◽  
First Year Of Life

Objective. Early feeding and infant exposures have been suggested as potential risk factors for immunoglobulin E- (IgE-) mediated food allergy (FA). We aimed to evaluate the association between IgE-mediated FA in children and early exposures including the child’s nutritional status, breastfeeding and its duration, the age at which the solid food was first introduced, antibiotic exposure during the first year of life, and the child’s vitamin D status during infancy. Design. A case-control study. Setting and Subjects. Children aged 0–13 years were recruited from pediatric allergy and immunology clinics (PAICs) located at major government hospitals in Kuwait (total FA cases: n=100; boys = 67%), and healthy controls (n=100, boys 55%) were recruited from various vaccination units at primary healthcare centers. Results. Cow’s milk allergy was the most common type of FA. FA status was independently associated with the early exposures of exclusive breastfeeding (aOR = 15.55 (3.26–74.19), p=0.001), vitamin D deficiency or insufficiency during infancy (aOR = 5.42 (1.92–15.30), p=0.001), and antibiotic exposure during the first year of life (aOR = 5.00 (1.58–15.84), p=0.006). Conclusions. FA is highly prevalent among children in Kuwait, and our data indicate that early nutrition-related and antibiotic exposures are associated with FA risk.

AUTISM SPECTRUM DISORDERS FOLLOWING IN UTERO EXPOSURE TO ANTIEPILEPTIC DRUGS

Neurology ◽  
2009 ◽  
Vol 73 (12) ◽  
pp. 997-997 ◽  
Author(s):  
M. L. Evatt ◽  
M. R. DeLong ◽  
W. B. Grant ◽  
J. J. Cannell ◽  
V. Tangpricha
Keyword(s):  
Autism Spectrum Disorders ◽  
Antiepileptic Drugs ◽  
In Utero ◽  
Autism Spectrum ◽  
In Utero Exposure ◽  
Spectrum Disorders

scholarly journals Leptin levels at birth and infant growth: the EPOCH study

2014 ◽  
Vol 5 (3) ◽  
pp. 214-218 ◽  
Author(s):  
J. L. Kaar ◽  
J. T. Brinton ◽  
T. Crume ◽  
R. F. Hamman ◽  
D. H. Glueck ◽  
...  
Keyword(s):  
Cord Blood ◽  
Perinatal Outcomes ◽  
Epidemiological Studies ◽  
In Utero ◽  
Feedback Mechanism ◽  
Infant Growth ◽  
Sufficient Evidence ◽  
First Year ◽  
First Year Of Life ◽  
Maternal Overweight

Objective: To examine the association of cord blood leptin with body mass index (BMI) growth velocity from birth to 12 months of age among infants exposed and not exposed to over-nutrition in utero (defined as maternal overweight/obesity or presence of gestational diabetes). Methods: 185 infants enrolled in the Exploring Perinatal Outcomes among Children study (76 exposed and 109 not exposed) had leptin and insulin measured in cord blood. Longitudinal weight and length measures in the first 12 months of life (average 4 per participant) obtained from medical records were used to compute BMI growth rates. Mixed models were used to examine associations of cord blood leptin with growth. Results: Compared with unexposed infants, those exposed had significantly higher cord blood insulin (8.64 v. 6.97 uU/ml, P<0.01) and leptin levels (8.89 v. 5.92 ng/ml, P=0.05) as well as increased birth weights (3438.04 v. 3306.89 g, P=0.04). There was an inverse relationship between cord leptin levels and BMI growth from birth to 12 months of age (P=0.005); however, exposure to over-nutrition in utero did not significantly modify this association (P=0.59). Conclusion: We provide support of a possible operational feedback mechanism by which lower cord blood leptin levels are associated with faster infant growth in the first year of life. Our data do not tend to support the hypothesis that this mechanism is altered in infants exposed to over-nutrition in utero; however our sample is too small to provide sufficient evidence. Larger epidemiological studies are needed to elucidate the mechanisms responsible for increased propensity for obesity in exposed offspring.

scholarly journals 4444 The effect of early life antibiotics on gut microbiome and fecal bile acid concentrations in children

2020 ◽  
Vol 4 (s1) ◽  
pp. 146-147
Author(s):  
Alain Jesus Benitez ◽  
Jeffrey S. Gerber ◽  
Ceylan Tanes ◽  
Kyle Bittinger ◽  
Elliot S. Friedman ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bile Acid ◽  
Early Life ◽  
Bacterial Community Composition ◽  
Antibiotic Use ◽  
First Year ◽  
Antibiotic Exposure ◽  
Fecal Bile Acid ◽  
Gi Symptoms ◽  
First Year Of Life

OBJECTIVES/GOALS: The current proposal seeks to investigate the effect of early life antibiotic use in the development of functional gastrointestinal (GI) disorders. We propose that infants exposed to antibiotics will present with gut microbial dysbiosis, changes in fecal bile acid concentrations and develop more GI symptoms compared to unexposed children. METHODS/STUDY POPULATION: We analyzed fecal samples from 174 subjects at 12 months of age, of whom 52 were exposed to antibiotics in their first year of life. Of these, 33 subjects were sampled again at 24 months of age. DNA from 200mg of frozen stool (−80C) was isolated with the Qiagen DNeasy PowerSoil kit. Shotgun libraries were generated using the NexteraXT kit and sequenced on the Illumina HiSeq 2500 using 2x125 bp chemistry. Sequence data were analyzed using the Sunbeam metagenomics pipeline. The abundance of bacteria was estimated using Kraken version 2.0.8. Fecal bile acids will be quantified by liquid chromatography–mass spectrometry (LC-MS). RESULTS/ANTICIPATED RESULTS: Overall bacterial community composition at 12 or 24 months was not associated with antibiotic exposure (PERMANOVA test, Bray-Curtis distance). An increase in Enterobacteriaceae, in particular Escherichia coli, is a signature of antibiotic-induced dysbiosis, but also of early infant gut. Children with antibiotic exposure had slightly higher abundance of Escherichia coli compared to those with no exposure (p = 0.03). At 24 months, the abundance of Bacteroides caccae, a commensal gut species, was decreased for children exposed to antibiotics in the first year of life (fdr = 0.02). We will perform further analysis of bile acid modifying bacteria, fecal bile acid concentrations and correlate to GI symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest a significant but nuanced impact of early life antibiotic use on the composition of the gut microbiota. The association of antibiotic exposure with B. caccae and E. coli warrant further attention in the context of the rapidly developing early-life microbiome. CONFLICT OF INTEREST DESCRIPTION: The authors declare no conflicts of interest relevant to this work.

scholarly journals Early Introduction of Sugar-Sweetened Beverages and Caries Trajectories from Age 12 to 48 Months

2020 ◽  
Vol 99 (8) ◽  
pp. 898-906 ◽  
Author(s):  
E. Bernabé ◽  
H. Ballantyne ◽  
C. Longbottom ◽  
N.B. Pitts
Keyword(s):  
Dental Caries ◽  
Young Children ◽  
Later Life ◽  
Rate Of Change ◽  
First Year ◽  
Sugar Sweetened Beverages ◽  
Sweetened Beverages ◽  
The Mean ◽  
First Year Of Life ◽  
Over Time

Early exposure to sweet tastes predicts similar food preferences and eating behavior in later life and is associated with childhood obesity. The aim of this study was to explore the associations of early (during the first year of life) and subsequent intake of sugar-sweetened beverages (SSBs) with 4-y caries trajectories among Scottish young children. We used data from 1,111 Scottish children who were followed annually from age 12 to 48 mo (4 sweeps in total). SSB intake was reported by parents in every sweep. SSB intake was broken down into 2 components, the initial SSB intake and the deviation over time from that initial value. Childhood dental caries was clinically determined (including noncavitated and cavitated lesions) every year. The association of SSB intake with baseline decayed, missing, and filled tooth surfaces (dmfs) (intercept) and rate of change in dmfs over time (slope) was examined in 2-level linear mixed-effects models, with repeated observations nested within children. Both the initial SSB intake and the deviation from the initial SSB intake were positively associated with steeper caries trajectories. By sweep 4, the predicted mean dmfs difference was 1.73 between children with low and high initial SSB intake (1 standard deviation below and above the mean) and 1.17 between children with low and high deviation from their initial SSB intake (1 SD below and above the mean). The findings of this prospective study among Scottish young children provide evidence that the introduction of SSBs during the first year of life can put children in a trajectory of high levels of dental caries. They support current recommendations to avoid sugars for very young children and interventions targeting early feeding practices for caries prevention.

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