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Association of Antibiotics in

Infancy With Early Childhood


Obesity
L. Charles Bailey, MD, PhD; Christopher B. Forrest, MD, PhD; Peixin Zhang, PhD; Thomas M.
Richards, MS; Alice Livshits, BS; Patricia A. DeRusso, MD, MS

JAMA Pediatrics 2014;168(11):1063-1069.

Presented by: Dries Dorpmans, Ruben Derwael


Why the research was done

IMPORTANCE

One:
0
1
Prevention of obesity in children and adults is a public health imperative because it
is associated with significant health burdens

Two:
0
2
Infancy may be a critical period when environmental factors exert a lasting effect on
risk for obesity; identifying modifiable risk factors may help reduce this risk

Three:
0
3 There is a need to determine the influence of antibiotic use on early childhood obesity
given the large shifts in diet and environmental contacts in infancy, the national
burden of disease, and ample opportunity for improved antimicrobial use
Why the research was done

IMPORTANCE

1/3 10% 32% 68%


Children and < 2 year old 2 19 year old Adults
Adolescents

Prevalence of Obesity before 24 Obesity age 2 to Obesity in adults


1 in 3Obesity
children and monthsare obese
10% of children 19 yo
It is estimated that 32% of An estimated 68% of adult
adolescents in the United by the time they are 24 children of 2 to 19 years of Amerians are either
States are either months of age age are overweight or overweight or obese
overweight or obese obese
The idea

OBJECTIVE

To assess the impact of antibiotics


prescribed in infancy (ages 0-23
months) on obesity in early childhood
(ages 24-59 months)
How the research was set up

DESIGN, EXPOSURES AND OUTCOMES


DESIGN, SETTING AND
PARTICIPANTS
Cohort study spanning 2001-2013 using electronic health records.
Primary care practices affiliated with the Childrens Hospital of
Philadelphia in urban Philadelphia and the surrounding region.
Data was adjusted for demographic, practice, and clinical
covariates.
All children with annual visits at ages 0 to 23 months, as well as 1 or
more visits at ages 24 to 59 months, were enrolled. The cohort
comprised 64 580 children.
EXPOSURES

Treatment episodes for prescribed antibiotics were ascertained up to


23 months of age
MAIN OUTCOMES AND
MEASURES
Obesity outcomes were determined directly from anthropometric
measurements using National Health and Nutrition Examination
Survey 2000 body mass index norms
Percentages at each step in selection are computed by
reference to the prior step

How the research was set up

CONSTRUCTION OF STUDY SAMPLE


89057 5840 (7%): Excluded
Infants with primary for prematurity or small
care visit at 0-11mo for gestational age
assessed for eligibility

83217 (93%) 10193 (12%):


Term non-small-for- Excluded for lacking
gestational-age visit at age 12-23mo
infants

6399 (9%):
73024 (88%) Excluded for lacking
With recurring visit at age 24-59mo
visits

1145 (2%): Excluded


66625 (91%) 65480 (98%)
for inability to assess
With follow-up in With evaluable obesity
body mass index
outcome period included in analysis
Percentages in reference to the total number of patients
(65480)

Visualizing the data


BASELINE CHARACTERISTICS OF STUDY POPULATION ASSESSED OVER AGES 0 TO
23 MONTHS
SEX ETHNICITY PRACTICE LOCATION OF FIRT VISIT
NO. OF PRIMARY CARE VISITS
Female Male Non-Hispanic Hispanic Suburban Urban 20 1-10
4 22
26
34
49 51 96 66

26
26
15-19 11-14

AT PRIMARY CARE VISITS (MO.) CALENDAR YEAR OF FIRST VISIT INSURANCE COVERAGE
11669
<1 11144 11170 Private Public
10315 10689
77
41
5619
10 - 12 5 58
7 - 96 2007
2661
6
4-6 5 206 *Other (1%)
1-3 2001 2002 2003 2004 2005 2006 2007 2008 2009 *Self-Pay (<0,1%)
Know what youre talking about

Defining measurements

ANTIBIOTIC EXPOSURE STEROID EXPOSURE


All primary care visits between birth and Systemic prednisone, dexamethasone,
23 mo. hydrocortisone
Systemic antibacterial medications Topical and inhaled steroids were
Anitvirals and antifungals were excluded excluded

BROAD SPECTRUM ANTIBIOTICS CLINICAL DIAGNOSIS


2 line therapy according to guidelines
nd Were recorded before 24 mo.
All other systemic antibacterial Asthma, wheezing, bronchiolitis,
medication croup, otitis media, pharyngitis

NARROW SPECTRUM ANTIBIOTICS BODY MASS INDEX (KG/M2)


First-line therapy according to guidelines Recorded between 24-59 months
Penicillin and Amoxicillin Obese: > 94th percentile
Overweight: 85th 94th percentile
Visualizing the data

ANTIBIOTIC EXPOSURES AT 0 TO 23 MONTHS

KEY POINTS

69% of children exposed to


antibiotics at age 23 months

Average of 2.3 episodes of


antibiotic treatment

62% at least 1 exposure to


narrow spectrum antibiotic

41% at least 1 exposure to


broad spectrum antibiotic
Visualizing the data
IMPACT OF ANTIBIOTIC CLASS, FREQUENCY AND TIMING ON THE RISK FOR OBESITY

KEY POINTS

Increased risk with greater antibiotic


use; particularly > 4 exposures

No significant association:
Obesity and Narrow Spectrum AB

Significantly greater effects for earlier


exposure to broad spectrum AB

Other risk factors: Male sex, Urban


practice, public insurance, Hispanic
ethnicity, Asthma/wheezing and
steroid use
Visualizing the data
MULTIVARIATE ANALYSIS OF THE RISK FOR EARLY CHILDHOOD
OBESITY

KEY POINTS

Increased risk with greater antibiotic


use; particularly > 4 exposures

No significant association:
Obesity and Narrow Spectrum AB

Significantly greater effects for earlier


exposure to broad spectrum AB

Other risk factors: Male sex, Urban


practice, public insurance, Hispanic
ethnicity, Asthma/wheezing and
steroid use
Food for thought

DISCUSSION

WHAT WAS SHOWN WEAKNESSES


Repeated antibiotic use, particularly Unable to capture details through EHR
broad spectrum drugs, at younger then Unaware of effect of antibiotics on
24 months old is a risk factor for later confounders
obesity Data subject to poor capture of medications
POTENTIAL MODIFIABLE RISK FACTOR prescribed
FOR CHILDHOOD OBESITY FUTURE
Narrow spectrum AB are not associated Additional investigation will be required to
with obesity even after multiple address confounders, demographic contexts
exposures and other potential risk factors

STEROIDS
2nd most common prescribed medication in this
age group
Effect size similar to frequent antibiotic use
A final review of key points

CONCLUSIONS

Point 1

Repeated exposure to broad-


spectrum antibiotics before 24
months of age is associated with
early childhood obesity

Point 2

Narrowing antibiotic selection is


potentially a modifiable risk factor
for childhood obesity.
Lets recap

W-W-W-W-W

What Where
An observational cohort study using Primary care practices affiliated with the
electronic health records Childrens Hospital of Philadelphia including
both teaching clinics and private practices in
urban Philadelphia, Pennsylvania, and the
surrounding region
Who
L. Charles Bailey, MD, PhD; Christopher
B. Forrest, MD, PhD; Peixin Zhang, PhD; Why
Thomas M. Richards, MS; Alice Livshits, To assess the impact of antibiotics
BS; Patricia A. DeRusso, MD, MS prescribed in infancy (ages 0-23
When months) on obesity in early
Spanning 2001-2013 childhood (ages 24-59 months)
Published in 2014
TAKE HOME MESSAGE:
DONT GO BROAD IF YOU CAN KEEP IT NARROW