nej mo a 1506699

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The new england

journal of medicine

n engl j med 374;2 nejm.org January 14, 2016 113

established in 1812 January 14, 2016 vol. 374 no. 2

From the Cincinnati Children’s HospitalMedical Center (T.H.I., T.M.J., M.A.H.,M.H.Z., S.A.X.) and the University ofCincinnati (C.R.B.), Cincinnati, and Na-tionwide Children’s Hospital, Columbus(M.P.M.) — all in Ohio; the University ofPittsburgh Medical Center, Pittsburgh(A.P.C.); Texas Children’s Hospital, BaylorCollege of Medicine, Houston (M.L.B.);Women and Children’s Hospital, Univer-sity of Buffalo, Buffalo, NY (C.M.H.); Uni-versity of Alabama at Birmingham, Bir-mingham (M.K.C.); and the National

Institute of Diabetes and Digestive andKidney Diseases, Bethesda, MD (M.H.).Address reprint requests to Dr. Inge atCincinnati Children’s Hospital MedicalCenter, 3333 Burnet Ave., MLC 2023, Cin-cinnati, OH 45229-3026, or at [email protected].

* A complete list of investigators in theTeen-Longitudinal Assessment of Bar-iatric Surgery (Teen-LABS) Consortiumis provided in the Supplementary Ap-pendix, available at NEJM.org

This article was published on November 6,2015, and updated on December 10,2015, at NEJM.org.

N Engl J Med 2016;374:113-23.

DOI: 10.1056/NEJMoa1506699

Copyright © 2015 Massachusetts Medical Society.

BACKGROUND

Bariatric surgery is increasingly considered for the treatment of adolescents with severeobesity, but few prospective adolescent-specific studies examining the eff icacy and safetyof weight-loss surgery are available to support clinical decision making.

METHODS

We prospectively enrolled 242 adolescents undergoing weight-loss surgery at five U.S.centers. Patients undergoing Roux-en-Y gastric bypass (161 participants) or sleeve gastrec-tomy (67) were included in the analysis. Changes in body weight, coexisting conditions,cardiometabolic risk factors, and weight-related quality of life and postoperative complica-tions were evaluated through 3 years after the procedure.

RESULTS

The mean (±SD) baseline age of the participants was 17±1.6 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was53; 75% of the participants were female, and 72% were white. At 3 years after the proce-dure, the mean weight had decreased by 27% (95% confidence interval [CI], 25 to 29) inthe total cohort, by 28% (95% CI, 25 to 30) among participants who underwent gastricbypass, and by 26% (95% CI, 22 to 30) among those who underwent sleeve gastrectomy.By 3 years after the procedure, remission of type 2 diabetes occurred in 95% (95% CI, 85to 100) of participants who had had the condition at baseline, remission of abnormalkidney function occurred in 86% (95% CI, 72 to 100), remission of prediabetes in 76%(95% CI, 56 to 97), remission of elevated blood pressure in 74% (95% CI, 64 to 84), andremission of dyslipidemia in 66% (95% CI, 57 to 74). Weight-related quality of life also

improved significantly. However, at 3 years after the bariatric procedure, hypoferritinemia was found in 57% (95% CI, 50 to 65) of the participants, and 13% (95% CI, 9 to 18) ofthe participants had undergone one or more additional intraabdominal procedures.

CONCLUSIONS

In this multicenter, prospective study of bariatric surgery in adolescents, we found sig-nificant improvements in weight, cardiometabolic health, and weight-related quality oflife at 3 years after the procedure. Risks associated with surgery included specific micro-nutrient deficiencies and the need for additional abdominal procedures. (Funded by theNational Institute of Diabetes and Digestive and Kidney Diseases and others; Teen-LABSClinicalTrials.gov number, NCT00474318.)

a bs t r a c t

Weight Loss and Health Status 3 Years after Bariatric Surgeryin Adolescents

Thomas H. Inge, M.D., Ph.D., Anita P. Courcoulas, M.D., Todd M. Jenkins, Ph.D., Marc P. Michalsky, M.D.,Michael A. Helmrath, M.D., Mary L. Brandt, M.D., Carroll M. Harmon, M.D., Ph.D., Meg H. Zeller, Ph.D.,

Mike K. Chen, M.D., Stavra A. Xanthakos, M.D., Mary Horlick, M.D., and C. Ralph Buncher, Sc.D.,for the Teen-LABS Consortium*

The New England Journal of Medicine

Downloaded from nejm.org at UFC on March 20, 2016. For personal use only. No other uses without permission.

Copyright © 2016 Massachusetts Medical Society. All rights reserved.

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n engl j med 374;2 nejm.org January 14, 2016114

Th e n e w e n g l a n d j o u r n a l o f medicine

Severe obesity affects 4.4 million

children and adolescents in the UnitedStates,1 and few effective treatments are

available.2 Particular concern has centered onhealth problems among severely obese adoles-cents and possible treatment with bariatric sur-gery.3 Indeed, adolescent bariatric surgical case

volumes doubled from approximately 800 casesin 20034 to 1600 procedures in 2009.5 Few pro-spective studies have examined changes in body-mass index (BMI, the weight in kilograms di-

vided by the square of the height in meters) andoutcomes of the currently used surgical proce-dures, and little is known about clinical eventsafter bariatric surgery in adolescents.6,7

To address important questions regarding theefficacy and safety of bariatric surgery in adoles-cents, the Teen-Longitudinal Assessment of Bar-iatric Surgery (Teen-LABS) study collects longi-tudinal, prospective clinical and laboratory dataon teenagers undergoing bariatric surgery at fivecenters in the United States. The current reportpresents data on weight loss, coexisting condi-tions, weight-related quality of life, micronutri-ent levels, and additional abdominal proceduresduring the 3 years after the bariatric procedure.

Methods

Study Design and Participants

In this prospective, multicenter, observationalstudy, we enrolled consecutive adolescents (≤19 years of age) who were undergoing any bariatricsurgical procedure from March 2007 throughFebruary 2012 at participating centers. Thesteering committee, which is made up of theprincipal investigator at each site, in collabora-tion with the data coordinating center and theproject scientist from the National Institute ofDiabetes and Digestive and Kidney Diseases,designed and implemented the study. The proto-col and statistical analysis plan are available

with the full text of this article at NEJM.org. Thefirst author wrote the first draft of the manu-script, and all the authors participated in criticalreviews and editing. The protocol and data andsafety monitoring plans were approved by theinstitutional review board at each institution andby a data and safety monitoring board for thestudy as a whole. All participants provided writ-ten informed consent.

Data Collection

The standardized methods we used for data col-lection have been described previously.8,9 Follow-up data were collected at the 6-month, 1-year,2-year, and 3-year postoperative research visits.Most visits occurred at the clinical centers or atthe participant’s home; in 22 instances, assess-

ments were conducted through self-report (Fig.S1 in the Supplementary Appendix, available atNEJM.org). Research coordinators, nurse practi-tioners, and physicians were trained in protocolprocedures for the collection of data. For home

visits, a field examiner who was trained in pro-tocol procedures conducted a visit at the partici-pant’s residence. Data collected during study

visits were maintained in a central database bythe data coordinating center. Missed visits didnot necessarily indicate withdrawal from thestudy, because participants commonly returnedfor later visits even after missing a visit. Weight-related quality of life was assessed with the useof the total score from the Impact of Weight onQuality of Life–Kids10 instrument (scores rangefrom 0 to 100, with higher scores indicating abetter quality of life).

Definitions

Standard conventions were followed for the as-sessment of prevalence, remission, and incidenceof coexisting conditions, and micronutrients were

measured as described in the Supplementary Ap-pendix. Information on additional surgical andendoscopic procedures that were performed be-tween 31 days after bariatric surgery and the3-year study visit was collected with the use of ascripted interview at each visit.

Statistical Analysis

A complete description of the statistical methodsis provided in the Supplementary Appendix.Weight loss, quality of life, coexisting condi-tions, and micronutrient outcomes were evalu-

ated with the use of linear mixed and general-ized mixed models, with separate modelsaccording to surgical procedure. Each modelincluded only the study visit as the independentpredictor term. Estimates of least-squares meansand 95% confidence intervals were generated.These models addressed missing data values bymeans of the maximum-likelihood method,under the data-missing-at-random assumption.




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Weight Loss and Health Status after Bariatric Surgery

Sensitivity analyses were performed to evaluatethis assumption. Using linear interpolation, wegenerated body-weight values from the valuesat previous and subsequent visits. For weightsthat were missing at the 3-year follow-up visit,

we applied a conservative 10% increase fromthe latest visit. On the basis of these analyses,

the missing-at-random assumption was consid-ered to be reasonable (see the SupplementaryAppendix).

Event rates for subsequent abdominal proce-dures were calculated as the number of eventsthat occurred from 31 days after the procedurethrough the 3-year study visit (visit window, 2.5to 3.5 years), divided by person-years of observa-tion. Poisson regression with the logarithm ofperson-years as an offset parameter was used tocalculate unadjusted rates and 95% confidenceintervals (expressed per 300 person-years).

Results

Participants

We enrolled 242 participants in the study; 161(67%) underwent Roux-en-Y gastric bypass, 67(28%) underwent sleeve gastrectomy, and 14 (6%)underwent adjustable gastric banding. Becauseof the small size of the gastric-band cohort,these results were not included in the mainanalyses (see the Supplementary Appendix). At

baseline, 29% of the participants were in theearly teenage age groups (13 to 15 years of age),41% were in the middle age groups (16 to 17

years of age), and 30% were in the late agegroups (18 to 19 years of age) (Table 1). Themean BMI was 53 (range, 34 to 88); 98% of theparticipants had a BMI higher than 40. The ma-

jority of participants were from families withhousehold incomes of less than $50,000 per

year. The majority of caregivers had completedhigh school, and 40% had obtained some col-lege education.

Through the 3-year study end point, 99% ofthe cohort (225 of 228 participants) participatedactively and completed 88% of all postoperative

visits (805 of 912 visits) (Fig. S1 in the Supple-mentary Appendix). The rates of visit completionaccording to follow-up time point were 89% at6 months (203 of 228 participants), 90% at 1 year(205 of 228), 89% at 2 years (203 of 228), and85% at 3 years (194 of 228). A total of 89% of

the postoperative visits (715 of 805) were com-pleted at the clinical center and 8% (68 of 805)

were conducted at the participant’s home; 3%(22 of 805) were self-reported assessments con-ducted through telephone contact or electroniccorrespondence.

Anthropometric Changes

At 3 years, the mean weight reduction among allparticipants was 41 kg, with little increase inheight (Table 1). The mean percent weight loss

was 27% (95% confidence interval [CI], 25 to 29)in the overall cohort: 28% (95% CI, 25 to 30;P

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CharacteristicAll Participants

(N = 228)Gastric Bypass

(N = 161)Sleeve Gastrectomy

(N = 67)

Age — yr 17±1.6 17±1.5 17±1.7

Age group — no. (%)

13–15 yr 66 (29) 42 (26) 24 (36)

16–17 yr 94 (41) 71 (44) 23 (34)

18–19 yr 68 (30) 48 (30) 20 (30)

Sex — no. (%)

Female 171 (75) 126 (78) 45 (67)

Male 57 (25) 35 (22) 22 (33)

Race or ethnic background — no. (%)†

White 164 (72) 119 (74) 45 (67)

Black 50 (22) 35 (22) 15 (22)

Asian 1 (

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had had the condition at baseline and for whomdata were available (P

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others were considered to be related to the pro-cedure. A total of 24% of the procedures wereperformed within the first year after the bariat-ric procedure, 55% within the second year, and21% within third year. Upper endoscopic proce-dures (including stricture dilations) were per-formed in 29 participants (13%). One participant

with known type 1 diabetes died 3.3 years aftergastric bypass surgery, from complications of ahypoglycemic event.

Discussion

A majority of participants in our study had markedimprovements with respect to weight, obesity-related coexisting conditions, and quality of life.The emergence of specific micronutrient deficien-cies and the need for subsequent abdominal pro-

cedures indicate that there are also risks associ-ated with bariatric surgery in this age group.

The outcomes of bariatric surgery among ado-lescents beyond 1 year after the procedure haverarely been described.11,12 The mean decrease inBMI after 1 year among Teen-LABS participants

who underwent gastric bypass was similar to thatreported in seven previous studies involving 256adolescents (decreases of 16.5 and 17.2, respective-ly).11-17 In a study involving 53 younger adolescents(mean age, 14 years), a decrease of 20 in mean BMIand an increase of 5 cm in mean height was ob-served 3 years after sleeve gastrectomy.18 This de-crease in BMI was greater than the decrease of 13.1that was observed among participants who under-

went sleeve gastrectomy in our study, probably inpart because of the linear growth in the youngercohort, which was not seen in our cohort. In aggre-gate, these results suggest that adolescents can losea clinically significant amount of weight after bar-iatric surgery, with the majority of patients main-taining meaningful weight loss for at least 3 years.

Among adults who undergo gastric bypass,

remission of type 2 diabetes occurs in 50 to 70%,and remission of elevated blood pressure occursin 40%.19,20 We found remission of diabetes in 95%of participants who had type 2 diabetes at base-line in our study, a finding consistent with ourprevious findings in adolescents.21 This result,coupled with the findings of normalization ofelevated blood pressure in nearly 80% of our par-ticipants, leads us to hypothesize that adolescentsmay have a greater potential than adults for rever-sal of the cardiometabolic consequences of obe-sity. We further speculate that these improve-

ments with regard to weight, glycemic control,blood pressure, and dyslipidemia in adolescentsmay mitigate the progression of adverse anatomi-cal and physiological cardiovascular changes —changes that may be less reversible after the ac-cumulation of more pound-years later in life.22 Additional research may clarify the way in whichage, obesity duration, and the timing of surgerycould modify the response to surgical treatment.

Gastric bypass and gastric resection may affect

Figure 1. Weight Changes and Prevalence of Dyslipidemia during the 3-YearPeriod after Bariatric Surgery.

Panel A shows the modeled least-squares mean percent changes in weightfrom baseline at each study visit during the 3 years after Roux-en-Y gastric

bypass surgery (bypass) or vertical sleeve gastrectomy (sleeve). Panel B showsthe modeled least-squares mean prevalences of dyslipidemia at each study

visit during the 3 years after Roux-en-Y gastric bypass surgery (bypass) orvertical sleeve gastrectomy (sleeve). I bars in both panels represent 95%

confidence intervals.

P e r c e n t C h a n

g e f r o m B

a s e l i n e

5

−5

0

−10

−15

−25

−30

−20

−35

−400 0.5 1.0 2.0 3.0

Years of Follow-up

No. of ParticipantsBypassSleeve

B Prevalence of Dyslipidemia

A Weight Change from Baseline

Bypass

Sleeve

P a r t i c i p a n t s ( % )

100

80

90

70

60

40

30

50

20

10

00 0.5 1.0 2.0 3.0

Years of Follow-up

No. of ParticipantsBypassSleeve

16167

14056

14061

13758

13152

16065

13854

14257

13252

12544

Bypass

Sleeve




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T a b l e 2 .

P r e v a l e n c e a n d R e m i s s i

o n o f C o e x i s t i n g C o n d i t i o n s . *

C o n d i t i o n

B a s e l i n e

3 Y e a r s

O b s e r v e d P r e v a l e n c e o f C o n d i t i o n

M o d e l e d P r e v a l e n c e

o f C o n d i t i o n †

O b s e r v e d P r e v a l e n c e o f R e m i s s i o n ‡

M o d e l e d P r e v a l e n c e

o f R e m i s s i o n †

n o . o f p a t i e n t s /

t o t a l n o .

% (

9 5 % C

I )

% (

9 5 % C

I )


t o t a l n o .

% (

9 5 % C

I )

% (

9 5 % C

I )

T y p e 2 d i a b e t e s

T o t a l

2 9 / 2 2 5

1 3 ( 9 – 1 7 )

1 3 ( 8 – 2 0 )

1 9

/ 2 0

9 5 ( 8 5 – 1 0 0 )

9 0 ( 6 5 – 9 8 )

G a s t r i c b y p a s s

2 3 / 1 5 9

1 4 ( 9 – 2 0 )

1 4 ( 9 – 2 3 )

1 7

/ 1 8

9 4 ( 8 4 – 1 0 0 )

9 4 ( 6 6 – 9 9 )

S l e e v e g a s t r e c t o m y

6 / 6 6

9 ( 2 – 1 6 )

9 ( 3 – 2 2 )

2

/ 2

1 0 0 ( 1 0 0 – 1 0 0 )

6 8 ( 7 – 9 9 )

P r e d i a b e t e s

T o t a l

1 9 / 1 9 4

1 0 ( 6 – 1 4 )

1 0 ( 6 – 1 7 )

1 3

/ 1 7

7 6 ( 5 6 – 9 7 )

7 7 ( 4 8 – 9 2 )


1 7 / 1 3 5

1 3 ( 7 – 1 8 )

1 3 ( 7 – 2 2 )

1 1

/ 1 5

7 4 ( 5 1 – 9 6 )

9 4 ( 6 6 – 9 9 )


2 / 5 9

3 ( 0 – 8 )

— §

2

/ 2

1 0 0 ( 1 0 0 – 1 0 0 )

— §

D y s l i p i d e m i a

T o t a l

1 7 1 / 2 2 5

7 6 ( 7 0 – 8 2 )

7 6 ( 6 9 – 8 1 )

8 4

/ 1 2 8

6 6 ( 5 7 – 7 4 )

6 6 ( 5 6 – 7 4 )


1 2 6 / 1 6 0

7 9 ( 7 2 – 8 5 )

7 9 ( 7 1 – 8 5 )

6 6

/ 9 5

6 9 ( 6 0 – 7 9 )

7 0 ( 5 9 – 7 9 )


4 5 / 6 5

6 9 ( 5 8 – 8 0 )

6 9 ( 5 5 – 8 0 )

1 8

/ 3 3

5 5 ( 3 8 – 7 2 )

5 5 ( 3 6 – 7 3 )

E l e v a t e d b l o o d p r e s s u r e

T o t a l

9 6 / 2 2 4

4 3 ( 3 6 – 4 9 )

4 3 ( 3 5 – 5 1 )

5 6

/ 7 6

7 4 ( 6 4 – 8 4 )

7 3 ( 6 0 – 8 3 )


7 3 / 1 5 9

4 6 ( 3 8 – 5 4 )

4 6 ( 3 7 – 5 5 )

4 7

/ 6 0

7 8 ( 6 8 – 8 9 )

7 8 ( 6 4 – 8 8 )


2 3 / 6 5

3 5 ( 2 4 – 4 7 )

3 5 ( 2 3 – 5 0 )

9

/ 1 6

5 6 ( 3 2 – 8 1 )

5 3 ( 2 7 – 7 8 )

A b n o r m a l k i d n e y f u n c t i o n

T o t a l

3 6 / 2 1 2

1 7 ( 1 2 – 2 2 )

1 7 ( 1 2 – 2 3 )

1 9

/ 2 2

8 6 ( 7 2 – 1 0 0 )

8 6 ( 6 3 – 9 0 )


2 9 / 1 5 3

1 9 ( 1 3 – 2 5 )

1 9 ( 1 3 – 2 7 )

1 6

/ 1 9

8 4 ( 6 8 – 1 0 0 )

8 4 ( 5 9 – 9 5 )


7 / 5 9

1 2 ( 4 – 2 0 )

1 2 ( 6 – 2 4 )

3

/ 3

1 0 0 ( 1 0 0 – 1 0 0 )

— §

* T h e c r i t e r i a u s e d t o d e f i n e e a c h

c o e x i s t i n g c o n d i t i o n a r e p r o v i d e d i n t h e S u

p p l e m e n t a r y A p p e n d i x .

† G e n e r a l i z e d m i x e d m o d e l s w e r e

u s e d t o c a l c u l a t e t h e m o d e l e d r e s u l t s .

‡ T h e p r o p o r t i o n o f p a r t i c i p a n t s i n r e m i s s i o n w a s c a l c u l a t e d a s t h e n u m b e r o f p a r t i c i p a n t s ( a m o n g t h o s e f o r w h o m s u f f i c i e n t d a t a w e r e a v a i l a b l e a t 3 y e a r s t o d e t e r m i n e w h e t h e r t h e c o -

e x i s t i n g c o n d i t i o n w a s p r e s e n t ) w h o d i d n o t h a v e t h e c o n d i t i o n a t 3 y e a r s a f t e r t h e p r o c e d u r e , d i v i d e d b y t h e n u m b e r

o f p a r t i c i p a n t s ( a m o n g t h o s e f o r w h o m s u

f f i c i e n t d a t a w e r e a v a i l -

a b l e a t 3 y e a r s t o d e f i n e w h e t h e r t h e c o e x i s t i n g c o n d i t i o n w a s p r e s e n t ) w h o h a d h a d t h e c o n d i t i o n a t b a s e l i n e .

§ T h e m o d e l f a i l e d b e c a u s e o f t h e

s m a l l s a m p l e s i z e .




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T a b l e 3 .

N u t r i t i o n a l a n d R e l a t e d

A b n o r m a l i t i e s . *

A b n o r m a l i t y

B a s e l i n e

3 Y e a r s

P V a l u e †

O b s e r v e d P r e v a l e n c e

M o d e l e d P r e v a l e n c e ‡




t o t a l n o .

% (

9 5 % C

I )

% (

9 5 % C

I )


t o t a l n o .

% (

9 5 % C

I )

% (

9 5 % C

I )

L o w a l b u m i n l e v e l

T o t a l

7 / 2 2 5

3 ( 1 – 5 )

— §

0 / 1 7 1

0

— §

—


7 / 1 6 0

4 ( 1 – 8 )

— §

0 / 1 2 7

0

— §

—


0 / 6 5

0

— §

0 / 4 4

0

— §

—

L o w f o l a t e l e v e l

T o t a l

6 / 1 7 3

3 ( 1 – 6 )

3 ( 1 – 7 )

1 0 / 1 3 2

8 ( 3 – 1 2 )

7 ( 4 – 1 4 )

0 . 1 3


4 / 1 2 6

3 ( < 1 – 6 )

3 ( 1 – 8 )

6 / 1 0 0

6 ( 1 – 1 1 )

6 ( 3 – 1 3 )

0 . 2 9


2 / 4 7

4 ( 0 – 1 0 )

4 ( 1 – 1 6 )

4 / 3 2

1 2 ( 1 – 2 4 )

1 0 ( 3 – 2 8 )

0 . 2 8

L o w v i t a m i n B 1 2 l e v e l

T o t a l

1 / 2 2 2

< 1 ( 0 – 1 )

< 1 ( < 1 – 3 )

1 3 / 1 6 0

8 ( 4 – 1 2 )

8 ( 4 – 1 4 )

0 . 0 0 5


1 / 1 5 9

1 ( 0 – 2 )

1 ( < 1 – 4 )

1 0 / 1 2 1

8 ( 3 – 1 3 )

8 ( 4 – 1 5 )

0 . 0 1


0 / 6 3

0

— §

3 / 3 9

8 ( 0 – 1 6 )

— §

—

L o w 2 5 - h y d r o x y v i t a m i n D l e v e l

T o t a l

8 3 / 2 2 3

3 7 ( 3 1 – 4 4 )

3 7 ( 3 0 – 4 5 )

7 4 / 1 7 2

4 3 ( 3 6 – 5 0 )

4 2 ( 3 4 – 5 0

)

0 . 3 7


7 1 / 1 5 9

4 5 ( 3 7 – 5 2 )

4 5 ( 3 6 – 5 4 )

6 1 / 1 2 8

4 8 ( 3 9 – 5 6 )

4 7 ( 3 8 – 5 7

)

0 . 6 4


1 2 / 6 4

1 9 ( 9 – 2 8 )

1 9 ( 1 0 – 3 2 )

1 3 / 4 4

3 0 ( 1 6 – 4 3 )

2 7 ( 1 4 – 4 4

)

0 . 3 6

H i g h p a r a t h y r o i d h o r m o n e l e v e l

T o t a l

1 8 / 2 2 3

8 ( 5 – 1 2 )

8 ( 5 – 1 3 )

1 6 / 1 7 2

9 ( 5 – 1 4 )

9 ( 5 – 1 5 )

0 . 7 7


1 7 / 1 5 9

1 1 ( 6 – 1 5 )

1 1 ( 6 – 1 8 )

1 5 / 1 2 8

1 2 ( 6 – 1 7 )

1 2 ( 7 – 1 9 )

0 . 8 5


1 / 6 4

2 ( 0 – 5 )

— §

1 / 4 4

2 ( 0 – 7 )

— §

—

L o w f e r r i t i n l e v e l

T o t a l

1 1 / 2 2 5

5 ( 2 – 8 )

5 ( 3 – 9 )

9 8 / 1 7 1

5 7 ( 5 0 – 6 5 )

5 7 ( 4 9 – 6 5

)

< 0 . 0 0 1


4 / 1 6 0

2 ( < 1 – 5 )

3 ( 1 – 7 )

8 3 / 1 2 7

6 5 ( 5 7 – 7 4 )

6 6 ( 5 6 – 7 4

)

< 0 . 0 0 1


7 / 6 5

1 1 ( 3 – 1 8 )

1 1 ( 5 – 2 2 )

1 5 / 4 4

3 4 ( 2 0 – 4 8 )

3 2 ( 1 9 – 5 0

)

0 . 0 1

H i g h t r a n s f e r r i n l e v e l

T o t a l

7 / 2 2 5

3 ( 1 – 5 )

3 ( 1 – 7 )

2 7 / 1 7 1

1 6 ( 1 0 – 2 1 )

1 6 ( 1 1 – 2 4

)

< 0 . 0 0 1


5 / 1 6 0

3 ( < 1 – 6 )

3 ( 1 – 8 )

2 5 / 1 2 7

2 0 ( 1 3 – 2 7 )

2 0 ( 1 3 – 2 9

)

< 0 . 0 0 1


2 / 6 5

3 ( 0 – 7 )

3 ( 1 – 1 3 )

2 / 4 4

5 ( 0 – 1 1 )

5 ( 1 – 1 9 )

0 . 6 3




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the absorption of numerous micronutrients thatare necessary for normal metabolism and for goodbone, hematologic, and nervous system health;therefore, multivitamin and mineral supplemen-tation is needed, as was prescribed in this cohort.The greatest changes that we observed were inmeasures related to iron and vitamin B

12. Iron-

deficiency anemia and vitamin B12 deficiency af-ter gastric bypass are well described.23,24 Vita-min B

12 deficiency was not unexpected after

sleeve gastrectomy, and it presumably relates toa reduction in intrinsic factor production after theprocedure. These results, as well as the decreased

vitamin A levels after gastric-bypass surgery,highlight the importance of long-term follow-upto evaluate nutritional measures, as well as theimportance of ensuring that appropriate supple-mentation is provided to minimize the develop-ment of clinically significant nutritional defi-ciencies in adolescents after bariatric surgery.

There are currently few available data regard-ing the need for subsequent abdominal opera-tions after bariatric surgery in adolescents. Ourdata, which include information on additionalconditions and procedures, may elucidate thetypes and frequencies of the adverse effects ofbariatric surgery in this age group. Previously,

we reported that 8% of the participants in ourstudy had major complications within 30 daysafter the bariatric procedure,9 and here we report

that 13% of the participants underwent addi-tional intraabdominal procedures within thesubsequent 3 years. The risks of complicationsmay differ according to the type of bariatricprocedure; however, the current study was notdesigned to identify such differences. Furtherstudy of larger cohorts and other populationsmay provide insight regarding this question.

The strengths of the current study include theprospective enrollment of consecutive patients atgeographically distinct sites, the standardizedmethods used to collect data, and strong cohort

maintenance over time. The limitations of ourstudy include the small size of certain importantsubpopulations, such as patients with diabetes. Inaddition, the observational nature of the studyintroduces heterogeneity into the data set, includ-ing unmeasured covariates and imbalances inrace, sex, and socioeconomic status. Without anon–surgically treated control group, it is difficultto place the postoperative changes in weight andhealth status completely into perspective, since






t o t a l n o .

% (

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% (

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)

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H i g h v i t a m i n B 1 e r y t h r o c y t e

t r a n s k e t o l a s e a c t i v i t y

T o t a l

2 / 2 1 7

1 ( 0 – 2 )

— §

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1 ( 0 – 2 )

— §

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1 ( 0 – 3 )

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1 ( 0 – 4 )

— §

—


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0

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0

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—

* T h e r e f e r e n c e r a n g e s u s e d t o d e

t e r m i n e a b n o r m a l v a l u e s a r e p r o v i d e d i n t h e S u p p l e m e n t a r y A p p e n d i x .

† P v a l u e s a r e f o r t h e c o m p a r i s o n

b e t w e e n t h e v a l u e a t 3 y e a r s a n d t h e v a l u e

a t t h e b a s e l i n e v i s i t .

‡ G e n e r a l i z e d m i x e d m o d e l s w e r e

u s e d t o c a l c u l a t e t h e m o d e l e d r e s u l t s .

§ T h e m o d e l f a i l e d b e c a u s e o f t h e

s m a l l s a m p l e s i z e .




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T a b l e 4 .

I n t r a a b d o m i n a l O p e r a t i o n s a n d O t h e r R e l a t e d P r o c e d u r e s f r o m 3

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* D a t a a r e f o r e v e n t s t h a t o c c u r r e d t h r o u g h t h e 3 - y e a r f o l l o w - u p v i s i t ( v i s i t w i n d o w , 2 . 5 t o 3 . 5 y e a r s ) . N A d e n o t e s n o t a p p l i c a b l e .




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behavioral treatment can result in modest im-provements in weight and cardiometabolic health.However, it has been reported that severely obeseadolescents who undergo nonsurgical treatmentdo not have major reductions in weight, and thereductions that they do have are not maintainedover 2 years of follow-up.25 Finally, despite a rela-

tively low 3-year missed-visit rate of 15%, missingdata — particularly data from laboratory testing,

which were missing in 24% of participants — isa limitation. However, statistical techniques thataddress missing data were applied, and sensitivityanalyses indicated that our assumptions with re-gard to patterns of missing data were reasonable.

In conclusion, we documented the durabilityof clinically meaningful weight loss and im-provements in key health conditions and weight-related quality of life among adolescents whounderwent gastric bypass surgery or sleeve gas-trectomy. These benefits must be viewed in the

context of the risks of micronutrient deficienciesand the possibility that future abdominal proce-dures will be needed in some patients. Studiesthat assess the longer-term durability of weightloss, potential improvements with respect tocoexisting conditions, and the risk of adverseevents, as well as the cost, may provide a better

understanding of the role of bariatric surgery inthe treatment of severe obesity in adolescents.

The content is solely the responsibility of the authors anddoes not necessarily represent the official views of the NationalInstitutes of Health.

Supported by grants from the National Inst itute of Diabetesand Digestive and Kidney Diseases, National Institutes of Health(U01DK072493 and UM1DK072493 to Dr. Inge, UM1DK095710 toDr. Buncher, UL1TR000077-04 to Cincinnati Children’s HospitalMedical Center, UL1RR025755 to Nationwide Children’s Hospi-tal, M01-RR00188 to Texas Children’s Hospital/Baylor Collegeof Medicine, UL1RR024153 and UL1TR000005 to the Universityof Pittsburgh, and UL1TR000165 to the University of Alabama,Birmingham).

Disclosure forms provided by the authors are available withthe full text of this article at NEJM.org.

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18. Alqahtani AR, Elahmedi MO, Al Qah-tani A. Co-morbidity resolution in mor-bidly obese children and adolescents un-dergoing sleeve gastrectomy. Surg ObesRelat Dis 2014;10:842-50.19. Schauer PR, Bhatt DL, Kirwan JP, et al.Bariatric surgery versus intensive medicaltherapy for diabetes — 3-year outcomes.N Engl J Med 2014;370:2002-13.20. Courcoulas AP, Christian NJ, Belle SH,et al. Weight change and health outcomes

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