Upload
vincent-dennis
View
215
Download
0
Embed Size (px)
Citation preview
Maternal prepregnancy body mass index and congenital heart defects: Preliminary results from the National
Birth Defects Prevention Study, 1997-2003
Adolfo Correa, Suzanne M. Gilboa, Lilah M. Besser, Lorenzo Botto, Sonja A. Rasmussen, D. Kim Waller, Charlotte A. Hobbs, Mario Cleves, Tiffany Riehle-Colarusso
Disclaimer: The findings and conclusions in this presentation have not been formally disseminated by CDC and should not be construed to represent any
agency determination or policy.
National Center on Birth Defects and Developmental Disabilities
Body Mass Index
Body mass index (BMI) proxy for % body fat
Increasing prevalence of overweight and obesity
Obesity Class
NHLBI Cutpoints (kg/m2) IOM Cutpoints (kg/m2)
Underweight <18.5 <19.8
Normal 18.5 - 24.9 19.8 - 26.0
Overweight 25.0 - 29.9 >26.0 - 29.0
Obesity I 30.0 - 34.9 >29.0
II 35.0 - 39.9
Extreme obesity III >40
1998
Obesity Trends* Among U.S. AdultsBRFSS, 1990, 1998, 2006
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2006
1990
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Prevalence among women 20-39 years of age
(Ogden et al. 2006. JAMA)
Years Overweight or obesity
BMI > 25
Obesity
BMI > 30
Extreme obesity
BMI > 40
1999-2000 54.4 28.3 6.0
2001-2002 54.7 29.8 5.0
2003-2004 51.7 28.9 8.0
Obesity and Pregnancy Outcomes
Several adverse pregnancy outcomes associated with obesity Macrosomia (> 4000g or 4500g) Large for gestational age (> 90th %ile) Longer duration of labor C-sections Late fetal death
Obesity and Birth Defects Obesity is a risk factor for structural birth
defects, most consistently, for neural tube defects (NTDs) Naeye, 1990 Waller et al., 1994 Shaw et al., 1996 Watkins et al., 1996 Werler et al., 1996 Källén, 1998… Waller et al., 2007
Obesity and CHD
Association with congenital heart defects (CHD) in the aggregate
NBDPS data 1997-2002 (Waller et al. 2007) Overweight: 1.13 (1.01-1.26) Obese: 1.40 (1.24-1.59)
Prospective cohort 1984-1987 (Moore et al. 2000) Obese: PR = 0.89 (0.35-2.2)
Obesity and CHD Specific CHD phenotypes associated with
body mass index Shaw et al., 2000
Two California case-control studies (1987-1989; 1989-1991) Watkins and Botto, 2001
Atlanta Birth Defects Case Control Study (1968-1980) Watkins et al., 2003
Atlanta Birth Defects Risk Factor Surveillance Study (1993-1997) Cedergren and Källén, 2003
Swedish medical registries (1992-2001)
0.1
1
10
100
Con
otru
ncal
Def
ects
d-T
GA
Tet
ralo
gy o
f Fal
lot
All
Hea
rt D
efec
ts
All
Isol
ated
Hea
rt D
efec
ts
Con
otru
ncal
Def
ects
Tet
ralo
gy o
f Fal
lot
d-T
GA
RV
OT
O
VS
D o
r A
SD
VS
D
AS
D
All
Hea
rt D
efec
ts
Con
otru
ncal
Def
ects
Tet
ralo
gy o
f Fal
lot
d-T
GA
RV
OT
O
Sev
ere
RV
OT
O
LVO
TO
HLH
S
Coa
rct
VS
D o
r A
SD
VS
D
AS
D
All
Hea
rt D
efec
ts
All
Isol
ated
Hea
rt D
efec
ts
Tet
ralo
gy o
f Fal
lot
d-T
GA
HLH
S
Coa
rct
VS
D
AS
D
Shaw et al.,2000
Watkins and Botto, 2001* Watkins et al., 2003† Cedergren and Källén, 2003‡
AO
R a
nd
95%
CI
Research Objectives
To investigate the relation between prepregnancy body mass index and the occurrence of congenital heart defects among women without pregestational diabetes.
To investigate possible effect measure modification by gestational diabetes, folic acid supplement intake, and race/ethnicity.
National Birth Defects Prevention Study
Population-based case-control design AR, CA, GA (CDC), IA, MA, NC, NJ,
NY, TX, UT October 1,1997 - December 31, 2003 Cases: live births, stillbirths, or
terminations Controls: live births from vital records
or hospital data
Computer-assisted telephone interview Participation: CHD cases (72%);
Controls (69%)
CHD Classification: Two Axes* Axis 1: Heart complexity (Heart)
Simple: One primary cardiac lesion Association: At least two distinct cardiac lesions Complex
Axis 2: Extra-cardiac malformations (Baby) Isolated: No major extra-cardiac defects Multiple: Presence of major extra-cardiac defects Syndrome Complex
* Botto LD, et al. 2007. Seeking causes: Classifying and evaluating congenital heart defects in etiologic studies. Birth Defects Res Part A Clin Molec Teratol 79:714-727
Congenital Heart Defects(Simple, isolated)
Any heart defect (n=3390) Conotruncal defects (n=745)
Tetralogy of Fallot (n=377) d-transposition of the great
arteries (n=266) Atrioventricular septal defect (n=74) Anomalous pulmonary venous return
(n=120) Total anomalous pulmonary
venous return (n=100) Left ventricular outflow tract
obstruction defects (n=552) Hypoplastic left heart syndrome
(n=221) Coarctation of the aorta (COA)
(n=207) Aortic stenosis (n=116)
Right ventricular outflow tract obstruction defects (n=551) Pulmonary valve stenosis (n=400) Pulmonary atresia (n=74)
Septal defects (n=1348) Ventricular septal defect (VSD)
perimembranous (n=592) VSD muscular (n=138) Atrial septal defects (n=589)
Atrial septal defect secundum (n=464)
Atrial septal defect NOS (n=125) COA + VSD (n=101) ASD + VSD (n=263)
Exclusions Exclusion of cases with “complex” heart or baby
classification N = 358 cases
Exclusion of mothers with “pregestational” diabetes Type 1 or 2 diabetes diagnosed any time: before,
during, or after index pregnancy, or at unknown date N =185 cases; N = 26 controls
Exclusion of those with missing BMI N = 230 cases; N = 208 controls
Exposure and Covariates Self-reported height and weight
converted to body mass index and categorized (NHLBI)
Potential confounders Maternal age, race/ethnicity, education, parity,
smoking (B1-P1)*, supplemental folic acid intake (B1-P1), hypertension during pregnancy, household income
Study center – conditional logistic regression
* B1-P1 refers to the month before conception through the end of first month of pregnancy
Analysis
Analysis restricted to CHD outcomes with at least 50 isolated cases
Simple and multiple logistic regression Assessment of effect measure modification
using interaction terms and stratified models Presentation of results for simple, isolated
CHD
Results: BMI Distribution
BMI category (kg/m2)
Simple, isolated cases (n=3390)
Controls (n=4774)
N (%) N (%)
< 18.5 172 (5.1) 285 (6.0)
18.5 – 24.9 1794 (52.9) 2707 (56.7)
25.0 – 29.9 809 (23.9) 1056 (22.1)
> 30.0 615 (18.1) 726 (15.2)
28-29%
Results: Main EffectsSimple, Isolated Heart Defect No. Cases OR (95% CI) No. Cases OR (95% CI)
Any Heart Defect 809 1.20 (1.07,1.35) 615 1.22 (1.07,1.40)Conotruncal Defects 167 1.16 (0.95,1.43) 136 1.33 (1.06,1.67) Tetralogy of Fallot 86 1.15 (0.87,1.51) 75 1.36 (1.00,1.84) D-Transposition of the Great Arteries 54 1.00 (0.71,1.40) 41 1.16 (0.79,1.69)Atrioventricular Septal Defect 16 0.94 (0.50,1.75) 13 1.14 (0.59,2.19)Anomalous Pulmonary Venous Return 23 1.04 (0.62,1.75) 26 1.74 (1.05,2.88) Total Anomalous Pulmonary Venous Return 20 1.21 (0.69,2.14) 24 2.27 (1.32,3.91)Left Ventricular Outflow Tract Obstruction Defects 133 1.21 (0.96,1.52) 97 1.18 (0.90,1.53) Hypoplastic Left Heart Syndrome 58 1.48 (1.05,2.09) 44 1.38 (0.93,2.04) Coarctation of the Aorta 50 1.14 (0.79,1.64) 35 1.18 (0.78,1.79) Aortic Stenosis 23 0.91 (0.55,1.50) 16 0.82 (0.46,1.46)Right Ventricular Outflow Tract Obstruction Defects 145 1.34 (1.07,1.69) 107 1.35 (1.05,1.75) Pulmonary Atresia 22 1.49 (0.82,2.68) 9 0.99 (0.45,2.19) Pulmonary Valve Stenosis 107 1.41 (1.08,1.83) 85 1.46 (1.09,1.95)Septal Defects 325 1.19 (1.01,1.40) 236 1.11 (0.92,1.34) Ventricular Septal Defect Perimembranous 140 1.11 (0.88,1.39) 96 0.99 (0.76,1.29) Ventricular Septal Defect Muscular 37 1.83 (1.00,3.35) 17 1.15 (0.54,2.44) Atrial Septal Defects 147 1.25 (1.00,1.58) 115 1.21 (0.94,1.57) Atrial Septal Defect Secundum 117 1.28 (0.99,1.64) 93 1.20 (0.90,1.59) Atrial Septal Defect NOS 30 1.13 (0.70,1.83) 22 1.27 (0.75,2.14)Special Association: Coarctation of the Aorta + Ventricular Septal Defect* 17 0.74 (0.43,1.30) 14 0.81 (0.43,1.51)Special Association: Ventricular Septal Defect + Atrial Septal Defect* 62 1.24 (0.89,1.73) 50 1.37 (0.96,1.97)* Associated, Isolated Heart Defects
Overweight Obese
Results: GDM Stratification
0.1
1
10
100
1000
GDM NoGDM
GDM NoGDM
GDM NoGDM
GDM NoGDM
GDM NoGDM
GDM NoGDM
GDM NoGDM
GDM NoGDM
GDM NoGDM
GDM NoGDM
OW OB OW OB OW OB OW OB OW OB
Any Heart Defect Conotruncal Defects LVOTO Defects RVOTO Defects Septal Defects
Ad
just
ed O
R
Results: Race/Ethnicity Stratification
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
NH
W
NH
B
His
pani
c
OW OB OW OB OW OB OW OB OW OB
Any Heart Defect Conotruncal Defects LVOTO Defects RVOTO Defects Septal Defects
Ad
just
ed O
R
Study Limitations• Self-reported BMI
– Potential misclassification of exposure due to underestimation of weight and overestimation of height
• Missing data– BMI data is missing more frequently among Hispanic
mothers (due to missing height)
• Incomplete case ascertainment among elective terminations– Quality of ultrasound visualization is poorer among
obese mothers
Conclusions
• Overweight status and obesity are associated with increased risk for selected CHD
• Underweight status appears to be unassociated with CHD
• Gestational diabetes during index pregnancy may modify the effect of overweight and obesity– May reflect role of undiagnosed type 2 diabetes
• Some evidence of effect measure modification of both overweight status and obesity by Hispanic ethnicity
Supplemental Slides
Race/Ethnicity x BMI (Among Controls)*N (Row percents)
R/E Underweight Average weight
Overweight Obese Total
NHW 169 (5.7) 1769 (59.5) 616 (20.7) 419 (14.1) 2973
NHB 32 (5.5) 278 (47.9) 143 (24.7) 127 (21.9) 580
Hispanic 52 (5.5) 493 (52.0) 146 (25.9) 158 (16.7) 949
Other 31 (11.8) 161 (61.5) 49 (18.7) 21 (8.0) 262
4764
* n=10 controls with missing race data
Age x BMI (Among Controls)N (Row percents)
Maternal age
Underweight Average weight
Overweight Obese Total
< 20 65 (12.4) 324 (61.7) 89 (17.0) 47 (8.9) 525
20-24 90 (8.6) 538 (51.6) 247 (23.7) 168 (16.1) 1043
25-29 55 (4.4) 687 (55.5) 290 (23.4) 206 (16.6) 1238
30-34 56 (4.3) 747 (57.6) 288 (22.2) 206 (15.9) 1297
> 35 19 (2.8) 411 (61.3) 142 (21.2) 99 (14.8) 671
4774
Missing BMI Data
Race/Ethnicity
CHD Cases
(n=228*)
Controls
(n=205*)
Missing N (%)
NHW 26 (11.4) 18 (8.8)
NHB 13 (5.7) 2 (1.0)
Hispanic 182 (79.8) 170 (82.9)
Other 6 (2.6) 13 (6.3)
* Includes 1 CHD case and 2 controls missing race/ethnicity.