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. Author manuscript; available in PMC: 2013 Sep 1.
Published in final edited form as: Birth Defects Res A Clin Mol Teratol. 2012 Aug 18;94(9):701–713. doi: 10.1002/bdra.23060

Table 4.

Exposure to Nitrosatable Drugs During the First Trimester of Pregnancy and Isolated Oral Clefts by Estimated Intake of Total Nitrites, National Birth Defects Prevention Study, 1997–2005

Type of malformation Total nitrite intake mg/daya Type of drug exposure Cases Controls Unadjusted ORc 95% CI Adjusted ORd 95% CI
No. %b No. %b
Cleft lip alone < 3.02 No nitrosatable drug exposure 138 72.6 1543 75.7 Referent Referent Referent Referent
 Secondary amines 34 19.8 263 14.6 1.45 0.97, 2.15 1.38 0.91, 2.07
 Tertiary amines 23 14.3 254 14.1 1.01 0.64, 1.61 1.02e 0.63, 1.64
 Amides 16 10.4 147 8.7 1.22 0.71, 2.10 1.19 0.68, 2.08
3.02–4.56 No nitrosatable drug exposure 137 74.9 1523 74.0 Referent Referent Referent Referent
 Secondary amines 26 16.0 282 15.6 1.02 0.66, 1.59 1.01 0.65, 1.59
 Tertiary amines 23 14.4 280 15.5 0.91 0.58, 1.45 0.93e 0.58, 1.49
 Amides 18 11.6 181 10.6 1.11 0.66, 1.85 1.13 0.67, 1.91
>4.56 No nitrosatable drug exposure 134 70.9 1622 78.8 Referent Referent Referent Referent
 Secondary amines 28 17.3 229 12.4 1.48 0.96, 2.28 1.25 0.79, 1.96
 Tertiary amines 30 18.3 231 12.5 1.57 1.03, 2.39 1.46e 0.93, 2.27
 Amides 19 12.4 157 8.8 1.46 0.88, 2.43 1.36 0.80, 2.31
Cleft lip with cleft palate < 3.02 No nitrosatable drug exposure 235 72.5 1543 75.7 Referent Referent Referent Referent
 Secondary amines 42 15.2 263 14.6 1.05 0.74, 1.49 1.02 0.71, 1.46
 Tertiary amines 48 17.0 254 14.1 1.24 0.89, 1.74 1.21 0.85, 1.72
 Amides 30 11.3 147 8.7 1.34 0.88, 2.03 1.34 0.87, 2.07
3.02–4.56 No nitrosatable drug exposure 224 71.3 1523 74.0 Referent Referent Referent Referent
 Secondary amines 39 14.8 282 15.6 0.94 0.65, 1.35 0.96 0.66, 1.40
 Tertiary amines 52 18.8 280 15.5 1.26 0.91, 1.75 1.34 0.95, 1.90
 Amides 35 13.5 181 10.6 1.31 0.89, 1.94 1.31 0.87, 1.96
>4.56 No nitrosatable drug exposure 243 79.4 1622 78.8 Referent Referent Referent Referent
 Secondary amines 36 12.9 229 12.4 1.05 0.72, 1.53 1.12 0.75, 1.66
 Tertiary amines 36 12.9 231 12.5 1.04 0.71, 1.52 1.18 0.79, 1.75
 Amides 21 8.0 157 8.8 0.89 0.56, 1.44 1.00 0.61, 1.64
Cleft palate alone < 3.02 No nitrosatable drug exposure 189 78.8 1543 75.7 Referent Referent Referent Referent
 Secondary amines 31 14.1 263 14.6 0.96 0.64, 1.44 0.93 0.61, 1.40
 Tertiary amines 23 10.9 254 14.1 0.74 0.47, 1.16 0.76 0.48, 1.21
 Amides 16 7.8 147 8.7 0.89 0.52, 1.52 0.90e 0.52, 1.57
3.02–4.56 No nitrosatable drug exposure 161 70.6 1523 74.0 Referent Referent Referent Referent
 Secondary amines 34 17.4 282 15.6 1.14 0.77, 1.69 1.07 0.72, 1.60
 Tertiary amines 36 18.3 280 15.5 1.22 0.83, 1.78 1.23 0.82, 1.82
 Amides 23 12.5 181 10.6 1.20 0.76, 1.91 1.19e 0.74, 1.91
>4.56 No nitrosatable drug exposure 176 76.5 1622 78.8 Referent Referent Referent Referent
 Secondary amines 22 11.1 229 12.4 0.89 0.56, 1.41 0.85 0.52, 1.36
 Tertiary amines 23 11.6 231 12.5 0.92 0.58, 1.45 0.88 0.55, 1.42
 Amides 29 14.2 157 8.8 1.70 1.11, 2.61 1.57e 1.01, 2.45

Abbreviations: OR, odds ratio; CI, confidence interval.

a

Total nitrites = daily dietary nitrite intake + 5% of daily nitrate intake.

b

Percentages for no nitrosatable drugs are based on total participants with complete information while percentages for a given nitrosatable group exclude other nitrosatable groups in the denominator.

c

Crude and adjusted odds ratios include only cases and controls with complete information for drug exposures and covariates.

d

Adjusted for maternal age, race/ethnicity, education, smoking, study center, calorie intake, and folic acid supplementation during the first trimester.

e

Significant additive interaction (95% confidence levels for RERI and/or AP exclude 0).