Socioeconomic Status in Relation to Selected Birth Defects in a Large Multicentered US Case-Control Study

Abstract

This study examined individual and household socioeconomic status (SES) in relation to phenotypes of neural tube defects, orafacial clefts, and conotruncal heart defects using data from the National Birth Defects Prevention Study with 2,551 nonmalformed liveborn controls and 1,841 cases delivered in 1997–2000. The individual SES was measured by maternal and paternal education, occupation, and household income. All individual SES measures were combined to create a household SES index. Elevated risks were found for maternal low education in association with anencephaly and dextrotransposition of the great arteries (dTGA) (adjusted odds ratios (AORs) ≥ 1.4); paternal low education in association with anencephaly, cleft palate, tetralogy of Fallot (TOF), and dTGA (AORs ≥ 1.4); low household income in association with TOF (AOR = 1.4, 95% confidence interval (CI): 0.8, 2.5); maternal operator/laborer occupation in association with cleft palate, TOF, and dTGA (AORs ≥ 1.4); paternal operator/laborer occupation in association with spina bifida (AOR = 1.4, 95% CI: 1.0, 2.0); and either parent's unemployment in association with dTGA (AOR ≥ 1.4). Subjects with the lowest household SES index had the greatest risks of all selected birth defects except TOF. This study reveals consistently increased risks of selected birth defects in association with household SES index but not individual SES measures.

cleft lip, cleft palate, heart defects, congenital, neural tube defects, social class

Many studies in the United States and other countries reveal that socioeconomic status (SES) is associated with risks of neural tube defects, conotruncal defects, and orofacial clefts, though findings were not entirely consistent (1–19). Different measures of SES and different prevalences of birth defects across geographic populations may have contributed to the inconsistent findings to some extent. Although SES in relation to birth defects has been widely studied, few studies examined multiple SES measures simultaneously (5, 14), combined and compared parental SES effects, compared SES effects on different birth defects (5), or examined the gradient response of SES in relation to birth defects (3, 12, 14).

The National Birth Defects Prevention Study (NBDPS) is a large case-control study of many birth defects in multiple states in the United States (20). It presents a good opportunity to more rigorously investigate SES in relation to birth defects by examining multiple aspects of SES in relation to multiple birth defects simultaneously. This study examined maternal and paternal education, income, and occupation in relation to the risks of neural tube defects, conotrunal heart defects, and orofacial clefts using recently collected data from this population-based study.

MATERIALS AND METHODS

The NBDPS is an ongoing case-control study of about 30 different birth defects, started in 1997. Study protocol details have been described previously (20). In brief, cases were identified from birth defect surveillance systems in eight states (Arkansas, California, Iowa, Georgia, Massachusetts, New Jersey, New York, and Texas). Eligible as cases were singleton liveborn infants, fetal deaths, and fetuses prenatally diagnosed and electively terminated. One state included only liveborn and stillborn cases (Massachusetts), and two states included only liveborn cases (New Jersey, New York). Controls were liveborn infants without major birth defects, randomly selected from birth certificates or birth hospitals reflecting the same study populations as the cases. The mothers of case infants and control infants were interviewed in either English or Spanish by female interviewers using a computer-assisted telephone interview within 24 months after the estimated delivery date. The interview covered a wide range of exposures from 12 weeks before conception through delivery. The date of conception was estimated primarily from the date of the last menstrual period. Overall participation rates of the NBDPS were 68.7 percent for the controls and 70.8 percent for the cases.

Interview data were available for a total of 1,841 cases and 2,551 controls with estimated dates of delivery from October 1, 1997, to December 31, 2000. This analysis included all controls and cases of neural tube defects (n = 380), cleft lip with or without cleft palate (n = 691), cleft palate alone (n = 391), and conotruncal heart defects (n = 397) (18 cases had more than one eligible defect). All cases were confirmed by clinical description or surgical or autopsy report and were further reviewed by a geneticist to exclude cases with recognized or strongly suspected single-gene disorders or chromosomal abnormalilites. This geneticist also classified each case as isolated if there was no additional major, unrelated defect or as nonisolated if there was at least one accompanying major, unrelated defect.

SES was measured by the mother's and the subject's biologic father's education, occupation, and household income. Education was the highest grade or years of school or college completed by each parent at the time of delivery. We included all occupations that the parents had from 12 weeks before conception through delivery. The NBDPS assigned an occupation code from the 2000 Standard Occupational Classification (SOC) system (http://www.bls.gov/soc/) to each job on the basis of job titles, job duties, company name, and what the company did. Because of the lack of an established method to categorize the 2000 SOC codes into SES levels, we devised a way to convert the 2000 SOC codes to the 1990 Census occupation codes. First, we assigned the 2000 SOC codes to the 2000 Census occupation codes using a crosswalk published by the US Census Bureau (21). The two codes are equivalent to each other but in different numeric systems. Second, we recoded the 2000 Census occupation codes to the 1990 Census occupation codes using another crosswalk (21). Finally, the 1990 US Census occupation codes 703–902, including machine operators, assemblers, inspectors, transportation and material-moving occupations, handlers, equipment cleaners, helpers, and laborers, were defined as lower SES (5, 14). Some of the 2000 SOC codes had multiple 1990 Census occupation codes in correspondence after the conversion, which in some instances resulted in conflicting SES levels for one job. To solve the problem, a trained specialist reviewed those jobs' titles, duties, company names, and what the company did (n = 1,465 jobs) and assigned them a single code of the 1990 Census occupation codes without knowing their case-control status. For mothers (n = 186) and fathers (n = 49) who had multiple jobs at different SES during the study period, one job was randomly selected for the analysis. Mothers and fathers who had no jobs from 12 weeks from conception through delivery were categorized as “unemployed.” Household income referred to the year before the mother became pregnant. It was collected in six categories and was reduced to three in our analysis: <$20,000, $20,000–$50,000, and >$50,000.

A household was assigned to “low” education if either parent received less than a high school education, “low” occupation if either parent was “operators/laborers,” and “low” income if the annual household income was less than $20,000. Otherwise, each of these parameters was assigned as “not low.” For examination of the joint effects of parental education, occupation, and household income in relation to birth defects, a household SES index was then created as the total number of “low” SES parameters that a household received based on the three SES measures, described above, categorized into “none low,” “only one low,” “only two low,” and “all low” groups.

Logistic regression models were constructed to estimate odds ratios and their 95 percent confidence intervals for maternal and paternal education and occupation and household income in relation to the risks of selected birth defects. Neural tube defects were split into spina bifida and anencephaly, and conotruncal heart defects were separated into tetralogy of Fallot (TOF) and dextrotransposition of the great arteries (dTGA) in the analysis. The mother's and father's education and occupation were evaluated separately and were also combined, as described above. Considered as potential confounders were maternal race/ethnicity (non-Hispanic White, non-Hispanic African American, and other); age (<25, 25–34, ≥35 years); state of residence (Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, and Texas); gravidity (one, two, three or more); obesity (prepregnant body mass index of >29.0 vs. ≤29.0 kg/m²); smoking during the month before conception or the first 3 months after conception (yes, no); binge drinking (≥5 drinks on a single occasion) during the month before conception or the first 3 months after conception (yes, no); and folic acid-containing multivitamin supplement use (use began during 3 months before pregnancy or the first month of pregnancy, use began in the second or third month of pregnancy vs. no use during those time periods). All analyses were conducted in Statistical Analysis System, version 8.2 (SAS Institute, Inc., Cary, North Carolina), software.

RESULTS

Distributions of demographic characteristics are presented in table 1 for infants with birth defects and nonmalformed control infants. Mothers of infants with birth defects were similar to mothers of infants without birth defects, with some exceptions. Relative to control mothers, case mothers were less likely to be African American, 25–34 years of age, and nonobese and to use folic acid-containing supplements before pregnancy or during the first month of pregnancy.

TABLE 1.

Characteristics of infants with birth defects and nonmalformed control infants, National Birth Defects Prevention Study, 1997–2000*,†

	Cases (%)	Controls (%)
Maternal race/ethnicity
Non-Hispanic White	61.5	61.2
Non-Hispanic African American	7.6	11.9
Hispanic	24.6	21.8
Other	4.8	3.7
Maternal age (years)
<25	36.9	33.8
25–34	48.8	52.7
≥35	14.3	13.5
Gravidity
0	29.1	30.0
1	29.8	28.9
2	18.5	21.6
≥3	22.2	19.2
Prepregnancy obesity
No	73.9	78.6
Yes	20.4	16.8
Periconceptional‡ smoking
No	77.3	79.5
Yes	21.7	19.7
Periconceptional binge drinking
No drinking	60.5	60.3
Non-binge drinking	28.7	29.1
Binge drinking	8.3	9.1
Folic acid-containing multivitamin supplement use
Use began during 3 months before pregnancy or the first month of pregnancy	47.1	50.8
Use began in the second or third month of pregnancy	34.0	34.0
No use or began after the third month of pregnancy	13.9	12.4

*

There were 1,841 cases and 2,551 controls.

†

Percentages may not equal 100 because of missing data or rounding.

‡

The “periconceptional period” refers to the month before conception and the first 3 months after conception.

Table 2 provides the percentage distribution of cases and controls by parental socioeconomic status. Eleven percent of controls (n = 230) were categorized into the “all low” household SES group, with either parent having less than a high school education, either parent in occupations of operator/laborer, and a household income of less than $20,000 during the year before pregnancy. A total of 468 (18.3 percent) controls and 232 (12.6 percent) cases were not included in the household SES index definition because of missing either maternal (n = 60) or paternal (n= 315) information on education and occupation or household income (n = 697).

TABLE 2.

Percentage distribution of cases and nonmalformed controls, by parental socioeconomic status, National Birth Defects Prevention Study, 1997–2000*

Socioeconomic status	Controls (%)	Spina bifida(%)	Anencephaly (%)	Cleft lip (%)	Cleft palate (%)	Tetralogy of Fallot (%)	Dextrotransposition of the great arteries (%)
Maternal education
≥4 years of college	29.4	19.0	17.8	24.9	27.4	26.8	29.9
<4 years of college	27.2	32.6	22.4	24.6	29.7	27.2	21.1
High school graduation	26.0	28.6	31.8	27.6	24.6	27.2	26.5
<High school graduation	16.2	19.0	26.2	21.9	17.4	17.2	21.1
Unknown	1.2	0.8	1.8	1.0	0.9	1.6	1.4
Paternal education
≥4 years of college	29.1	23.8	22.4	24.9	27.1	25.6	28.6
<4 years of college	21.2	20.1	15.9	20.4	23.3	21.2	20.4
High school graduation	30.4	31.5	31.8	32.4	29.2	34.0	29.9
<High school graduation	15.0	20.9	22.4	17.1	15.1	15.2	17.0
Unknown	4.3	3.7	7.5	5.2	5.3	4.0	4.1
Household income
>$50,000	28.1	20.5	23.4	25.5	30.2	33.6	34.0
$20,000–$50,000	28.2	30.4	26.2	28.8	28.6	26.0	25.2
<$20,000	25.4	34.1	35.5	33.9	28.1	30.4	27.9
Unknown	18.3	15.0	14.9	11.8	13.1	10.0	12.9
Maternal occupation
Other occupation	70.0	67.4	57.0	64.7	66.8	66.8	62.6
Operator/laborer	3.8	4.4	3.7	3.8	5.1	5.2	4.8
Unemployed	25.0	27.5	37.4	30.7	27.1	26.4	31.3
Unknown	1.2	0.7	1.9	0.8	1.0	1.6	1.3
Paternal occupation
Other occupation	74.6	67.4	62.6	67.1	70.3	73.2	74.8
Operator/laborer	15.7	23.4	19.6	20.1	18.9	14.8	12.9
Unemployed	5.0	3.7	8.4	7.1	5.4	5.6	7.5
Unknown	4.7	5.5	9.4	5.7	5.4	6.4	4.8
Household SES† index‡
None low	36.4	27.8	24.3	32.9	36.8	38.4	36.5
Only one low	22.7	27.8	27.1	24.0	23.8	23.6	27.2
Only two low	13.5	15.8	15.9	15.9	14.1	18.0	11.6
All low	9.0	13.6	16.8	15.3	12.3	10.0	12.2
Unknown	18.4	15.0	15.9	11.9	13.0	10.0	12.9

*

The numbers of controls and cases were as follows: controls, 2,551; spina bifida, 273; anencephaly, 107; cleft lip, 691; cleft palate, 391; tetralogy of Fallot, 250; dextrotransposition of great arteries, 147.

†

SES, socioeconomic status.

‡

Refer to Materials and Methods for explanation.

Tables 3– ⁴5 present the crude and adjusted odds ratios of the SES measures in relation to the selected birth defects. Individual SES indicators were adjusted by each other and by the other potential confounders to generate the final adjusted odds ratios. The SES index was adjusted only by potential confounders. All analyses were repeated with isolated cases and again excluding cases and controls with self-reported family histories. The findings did not change substantially (results not shown).

TABLE 3.

Crude odds ratios, adjusted odds ratios, and their 95% confidence intervals for parental socioeconomic status in relation to neural tube defects, National Birth Defects Prevention Study, 1997–2000

Socioeconomic status	Spina bifida				Anencephaly
	Crude odds ratio	95% confidence interval	Adjusted odds ratio*	95% confidence interval	Crude odds ratio	95% confidence interval	Adjusted odds ratio	95% confidence interval
Maternal education
≥4 years of college	Referent		Referent		Referent		Referent
<4 years of college	1.9	1.3, 2.6	1.3	0.8, 2.1	1.4	0.7, 2.5	1.2	0.6, 2.6
High school graduation	1.7	1.2, 2.4	1.3	0.7, 2.3	2.0	1.1, 3.6	1.4	0.6, 3.4
<High school graduation	1.8	1.2, 2.7	1.1	0.5, 2.2	2.7	1.5, 4.9	1.0	0.3, 3.0
Paternal education
≥4 years of college	Referent		Referent		Referent		Referent
<4 years of college	1.2	0.8, 1.7	0.9	0.5, 1.4	1.0	0.5, 1.8	0.9	0.4, 1.9
High school graduation	1.3	0.9, 1.8	0.9	0.5, 1.4	1.4	0.8, 2.3	1.0	0.5, 2.3
<High school graduation	1.7	1.2, 2.5	1.3	0.7, 2.4	1.9	1.1, 3.5	1.5	0.5, 4.0
Household income
>$50,000	Referent		Referent		Referent		Referent
$20,000–$50,000	1.5	1.0, 2.1	1.0	0.6, 1.6	1.1	0.6, 1.9	0.7	0.3, 1.3
<$20,000	1.8	1.3, 2.6	1.2	0.7, 2.0	1.7	1.0, 2.8	1.0	0.4, 2.2
Maternal occupation
Other occupation	Referent		Referent		Referent		Referent
Operator/laborer	1.2	0.6, 2.2	1.2	0.6, 2.3	—†		—
Unemployed	1.1	0.9, 1.5	0.9	0.6, 1.2	1.8	1.2, 2.8	1.2	0.7, 2.2
Paternal occupation
Other occupation	Referent		Referent		Referent		Referent
Operator/laborer	1.7	1.2, 2.2	1.4	1.0, 2.0	1.5	0.9, 2.5	1.3	0.7, 2.4
Unemployed	0.8	0.4, 1.6	0.6	0.2, 1.4	2.0	1.0, 4.1	0.9	0.3, 2.9
Household SES‡ index§
None low	Referent		Referent		Referent		Referent
Only one low	1.6	1.1, 2.2	1.5	1.0, 2.2	1.8	1.0, 3.1	1.6	0.9, 2.9
Only two low	1.5	1.0, 2.3	1.2	0.7, 1.9	1.8	0.9, 3.3	1.5	0.7, 3.3
All low	2.0	1.3, 3.0	1.5	0.9, 2.7	2.8	1.5, 5.2	2.3	1.0, 5.5

*

Education, household income, and occupation were adjusted by each other, plus by the covariates maternal race/ethnicity, age, state of residence, gravidity, obesity, smoking, binge drinking, and folic acid-containing multivitamin supplement use; the household socioeconomic status index was adjusted by only the non-socioeconomic status covariates. Subjects with a missing value for any included variables were excluded from the adjusted model.

†

—, sample size is less than 5.

‡

SES, socioeconomic status.

§

Refer to Materials and Methods for explanation.

TABLE 4.

Crude odds ratios, adjusted odds ratios, and their 95% confidence intervals for parental socioeconomic status in relation to orofacial clefts, National Birth Defects Prevention Study, 1997–2000

Socioeconomic status	Cleft lip (± palate)				Cleft palate
	Crude odds ratio	95% confidence interval	Adjusted odds ratio*	95% confidence interval	Crude odds ratio	95% confidence interval	Adjusted odds ratio	95% confidence interval
Maternal education
≥4 years of college	Referent		Referent		Referent		Referent
<4 years of college	1.1	0.8, 1.4	0.9	0.7, 1.3	1.2	0.9, 1.6	1.3	0.9, 1.9
High school graduation	1.3	1.0, 1.6	0.8	0.6, 1.2	1.0	0.8, 1.4	0.9	0.6, 1.4
<High school graduation	1.6	1.2, 2.0	1.0	0.6, 1.6	1.2	0.8, 1.6	0.9	0.5, 1.7
Paternal education
≥4 years of college	Referent		Referent		Referent		Referent
<4 years of college	1.1	0.9, 1.4	1.1	0.8, 1.5	1.2	0.9, 1.6	1.4	0.9, 2.0
High school graduation	1.2	1.0, 1.6	1.1	0.8, 1.5	1.0	0.8, 1.4	1.2	0.8, 1.8
<High school graduation	1.3	1.0, 1.7	1.0	0.7, 1.6	1.1	0.8, 1.5	1.4	0.8, 2.4
Household income
>$50,000	Referent		Referent		Referent		Referent
$20,000–$50,000	1.1	0.9, 1.4	1.1	0.8, 1.4	0.9	0.7, 1.3	1.0	0.7, 1.4
<$20,000	1.5	1.2, 1.8	1.2	0.8, 1.7	1.0	0.8, 1.4	1.3	0.8, 2.1
Maternal occupation
Other occupation	Referent		Referent		Referent		Referent
Operator/laborer	1.1	0.7, 1.7	1.0	0.6, 1.8	1.4	0.9, 2.3	1.4	0.8, 2.7
Unemployed	1.3	1.1, 1.6	1.2	1.0, 1.6	1.1	0.9, 1.5	1.2	0.9, 1.7
Paternal occupation
Other occupation	Referent		Referent		Referent		Referent
Operator/laborer	1.4	1.1, 1.8	1.2	0.9, 1.5	1.3	1.0, 1.7	1.3	0.9, 1.9
Unemployed	1.6	1.1, 2.2	1.3	0.8, 2.0	1.1	0.7, 1.8	1.1	0.6, 2.1
Household SES† index‡
None low	Referent		Referent		Referent		Referent
Only one low	1.2	0.9, 1.5	1.1	0.9, 1.4	1.0	0.8, 1.4	1.2	0.9, 1.7
Only two low	1.3	1.0, 1.7	1.1	0.8, 1.6	1.0	0.7, 1.4	1.3	0.8, 1.9
All low	1.9	1.4, 2.5	1.7	1.2, 2.5	1.3	0.9, 1.9	2.3	1.4, 3.8

*

Education, household income, and occupation were adjusted by each other, plus by the covariates maternal race/ethnicity, age, state of residence, gravidity, obesity, smoking, binge drinking, and folic acid-containing multivitamin supplement use; the household socioeconomic status index was adjusted by only the non-socioeconomic status covariates. Subjects with a missing value for any included variables were excluded from the adjusted model.

†

SES, socioeconomic status.

‡

Refer to Materials and Methods for explanation.

TABLE 5.

Crude odds ratios, adjusted odds ratios, and their 95% confidence intervals for parental socioeconomic status in relation to heart defects, National Birth Defects Prevention Study, 1997–2000

Socioeconomic status	Tetralogy of Fallot				Dextrotransposition of the great arteries
	Crude odds ratio	95% confidence interval	Adjusted odds ratio*	95% confidence interval	Crude odds ratio	95% confidence interval	Adjusted odds ratio	95% confidence interval
Maternal education
≥4 years of college	Referent		Referent		Referent		Referent
<4 years of college	1.1	0.8, 1.6	1.1	0.7, 1.9	0.8	0.5, 1.2	1.0	0.5, 1.8
High school graduation	1.1	0.8, 1.6	0.9	0.5, 1.6	1.0	0.6, 1.6	1.3	0.7, 2.6
<High school graduation	1.2	0.8, 1.7	0.8	0.4, 1.9	1.3	0.8, 2.1	1.5	0.6, 3.7
Paternal education
≥4 years of college	Referent		Referent		Referent		Referent
<4 years of college	1.1	0.8, 1.7	1.3	0.8, 2.2	1.0	0.6, 1.6	1.2	0.7, 2.2
High school graduation	1.3	0.9, 1.8	1.6	0.9, 2.6	1.0	0.7, 1.5	1.5	0.8, 2.8
<High school graduation	1.2	0.8, 1.8	1.4	0.7, 3.0	1.2	0.7, 1.9	1.1	0.4, 2.6
Household income
>$50,000	Referent		Referent		Referent		Referent
$20,000–$50,000	0.8	0.5, 1.1	1.0	0.6, 1.5	0.7	0.5, 1.1	0.6	0.3, 1.1
<$20,000	1.0	0.7, 1.4	1.4	0.8, 2.5	0.9	0.6, 1.4	0.7	0.3, 1.4
Maternal occupation
Other occupations	Referent		Referent		Referent		Referent
Operator/laborer	1.4	0.8, 2.6	2.2	1.0, 4.6	1.4	0.6, 3.1	2.5	1.0, 6.2
Unemployed	1.1	0.8, 1.5	1.1	0.7, 1.7	1.4	1.0, 2.0	1.4	0.9, 2.3
Paternal occupation
Other occupation	Referent		Referent		Referent		Referent
Operator/laborer	1.0	0.7, 1.4	0.8	0.5, 1.2	0.8	0.5, 1.4	0.7	0.3, 1.3
Unemployed	1.1	0.6, 2.0	0.8	0.3, 1.9	1.5	0.8, 2.9	2.0	0.9, 4.6
Household SES† index‡
None low	Referent		Referent		Referent		Referent
Only one low	1.0	0.7, 1.4	1.2	0.8, 1.7	1.2	0.8, 1.8	1.4	0.9, 2.3
Only two low	1.3	0.9, 1.8	1.1	0.6, 1.8	0.9	0.5, 1.5	1.0	0.5, 2.0
All low	1.1	0.7, 1.7	1.0	0.5, 2.0	1.4	0.8, 2.4	1.5	0.6, 3.4

*

Education, household income, and occupation were adjusted by each other, plus by the covariates maternal race/ethnicity, age, state of residence, gravidity, obesity, smoking, binge drinking, and folic acid-containing multivitamin supplement use; the household socioeconomic status index was adjusted by only the non-socioeconomic status covariates. Subjects with a missing value for any included variables were excluded from the adjusted model.

†

SES, socioeconomic status.

‡

Refer to Materials and Methods for explanation.

Crude and adjusted analyses revealed similar results for most individual SES measures in relation to cleft lip (without or without cleft palate), cleft palate, TOF, and dTGA, but not spina bifida and anencephaly. Most of the increased risks of spina bifida and anencephaly detected in the crude analysis became null when the individual SES measures were adjusted by each other and by the confounders. For brevity, the presentation of results highlights only the adjusted associations with risk estimates of ≥1.4 or ≤0.7.

There was a borderline association between spina bifida and father's occupation, but not other individual SES indicators (table 3). Operator/laborer fathers had an increased risk to have offspring with spina bifida (adjusted odds ratio (AOR) = 1.4, 95 percent confidence interval (CI): 1.0, 2.0), while unemployed fathers were at a decreased risk to have offspring with spina bifida (AOR = 0.6, 95 percent CI: 0.2, 1.4), although the result was imprecise. A lower level of education was associated with elevated risk of anencephaly: The adjusted odds ratio of ≥1.4 was observed for mothers with a high school education (AOR = 1.4, 95 percent CI: 0.6, 3.4) and for fathers with less than a high school education (AOR = 1.5, 95 percent CI: 0.5, 4.0) relative to 4 or more years of college education. Subjects with a middle level of household income at $20,000–$50,000 were at a slightly decreased risk to have anencephaly (AOR = 0.7, 95 percent CI: 0.3, 1.3) in comparison with subjects who had a household income greater than $50,000 during the pregnancy year. Analysis of the household SES index revealed moderately increased risk of both spina bifida and anencephaly in a comparison of lower household SES with the “none low” household SES. The adjusted odds ratios were 1.5 for “only one low” (95 percent CI: 1.0, 2.2) and “all low” (95 percent CI: 0.9, 2.7) household SES in relation to spina bifida and 1.6 (95 percent CI: 0.9, 2.9), 1.5 (95 percent CI: 0.7, 3.3), and 2.3 (95 percent CI: 1.0, 5.5) for “only one low,” “only two low,” and “all low” household SES in association with anencephaly.

There was no association between individual SES indicators and cleft lip (with or without cleft palate) (table 4). Less educated fathers and operator/laborer mothers had an increased risk to have offspring with cleft palate (both AORs = 1.4, 95 percent CIs: 0.8, 2.4 and 0.8, 2.7, respectively). Subjects with “all low” household SES were at increased risks to have infants with cleft lip (with or without cleft palate) (AOR = 1.7, 95 percent CI: 1.2, 2.5) and cleft palate (AOR = 2.3, 95 percent CI: 1.4, 3.8).

Mothers with less than a high school education were at higher risk to have dTGA offspring but not TOF, and the adjusted odds ratio was 1.5 (95 percent CI: 0.6, 3.7) in a comparison with 4 or more years of college. Paternal low education was associated with increased risks of TOF and dTGA; the adjusted odds ratios were 1.4 or greater, but confidence intervals included 1 (table 5). Households with lower income were more likely to have TOF offpsring (AOR = 1.4, 95 percent CI: 0.8, 2.5). Operator/laborer mothers were at two times greater risk to have offspring with TOF and dTGA (AOR ≥ 2.2), and either parent unemployed was more likely to have dTGA cases (AOR ≥ 1.4). Paternal occupation of operator/laborer and low household income were associated with a reduced risk of dTGA (AORs ≤ 0.7), but confidence intervals included 1. In a comparison of households with “none low” SES, households with “all low” SES or “only one low” SES were more likely to have dTGA cases (AORs ≥ 1.4). The household SES index was not associated with TOF occurrence.

DISCUSSION

This study found some evidence for an association of individual and household SES measures with specific phenotypes of neural tube defects, orofacial clefts, and conotruncal heart defects. However, many of the confidence intervals included 1. A comprehensive literature review revealed inconsistent findings of SES in association with orofacial clefts and conotruncal heart defects, because of the greatly varied case ascertainment, classification, and exclusion criteria, incomplete SES measurements, and simple descriptive analytical approaches in previous studies without controlling confounding effects and adjusting effect modification (5). Results for neural tube defects were more consistent across studies; higher risks of neural tube defects (including spina bifida and anencephaly) were reported in populations with lower socioeconomic status as measured by education (2–4, 8, 22–24), occupation (3, 7, 14, 25), and income (1, 3, 17). Similar to previous studies, this study revealed increased risks of anencephaly and spina bifida in association with education and household SES index.

Some studies have found lower education, lower occupation SES, or less income in association with orofacial clefts (26–35), while other studies report that SES measures are not associated with the risk of clefts (5, 9, 27, 36–42). We observed that lower SES, including lower paternal education and maternal occupation of operator/laborer, increased the risk of cleft palate only but not cleft lip. Adjusted results indicated that an “all low” score on the SES index was associated with an increased risk of both outcomes.

Previous studies showed no association between SES and the risk of conotruncal heart defects (18, 43–49). Several studies reported increased risks of lower SES in association with conotruncal heart defects (9, 50, 51) or certain phenotypes of conotruncal heart defects (5, 52), and three studies detected decreased risk of TOF in relation to lower SES (5, 50, 52). Adjusted results of this study suggested increased risks of TOF and dTGA in association with lower paternal education and maternal operator/laborer occupation, increased risk of TOF in association with low household income, and increased risk of dTGA associated with lower maternal education, either parent unemployed, and a low score on the SES index.

The socioeconomic gradient in health has been reported for many diseases, although not all (53). Studying the SES gradient contributes more information to establish pathways from SES to health outcomes (53). The SES gradient has been detected in relation to some birth defect phenotypes (3). The current study found the greatest risk of examined birth defect phenotypes in association with the lowest household SES and rough gradient associations of household SES index with anencephaly and cleft palate. In contrast, a consistent gradient association with a detailed SES index was not observed for conotruncal heart defects and orofacial clefts in a California population (5).

Lower SES is often considered to be a marker for other factors in the pathway to worse health outcomes. Our approach of adjusting for factors, such as smoking and folic acid-containing supplement intake, was to estimate the “direct” effect of SES on birth defects rather than effects mediated through these other factors. Education, occupation, and income are three common measures for SES. Education is the most stable indicator of SES that reflects a person's ability to access and interpret health-related information (54–56). Occupation is believed to influence health via workplace hazards exposure, psychosocial factors, and social networks (54, 55). Income relates directly to the material conditions that influence health, such as living condition, medical care, and lifestyle (55). Comparison of the effects measured by different SES indicators may provide clues to identify pathways linking SES to the studied health outcomes. This analysis revealed different associations of each SES indicator with the selected birth defects. However, the inconsistent findings preclude drawing firm inferences. The lowest household SES index in association with the greatest risk of most selected birth defects suggests that it might be the synchronized effects of multiple risk factors instead of a specific one that leads to the occurrence of birth defects.

Using data from the NBDPS gives this analysis several strengths, including large sample size, population-based ascertainment of cases and controls, standardized diagnostic rules for cases, and a geographically diverse US population base (57). Improvements of the current analysis compared with previous ones are that it examined multiple measures of SES simultaneously, it compared the SES-associated risks for several major birth defects, it investigated maternal and paternal SES indicators, it examined the gradient effect of a household SES index, and it adjusted for several potential confounders.

This study also has several limitations. First, the sample size was small for certain comparisons, although the NBDPS is a large national study. In addition, because of small sample size, both parents with low education or low occupation could not be separated from only one parent with low education or low occupation in the SES index definition as in a previous study (5). Second, this study did not examine the neighborhood SES effect. Socioeconomic status of neighborhoods may interact with individual-level SES in association with birth defects (5, 55). Third, about 16 percent of cases and controls had missing data on household income, which resulted in reduced power to detect an effect of household income and household SES index in association with the selected birth defects. Compared with subjects with known household income, cases and controls with unknown household income were more likely to have one parent with less than a high school education (34 percent vs. 23 percent) but less likely to have one parent with operator/laborer occupation (17 percent vs. 20 percent). In addition, controls (18 percent) were more likely to have unknown household income than were cases (15 percent for neural tube defect cases and around 12 percent for orofacial cleft and conotruncal heart defect cases). The different distribution of the unknown household income by SES levels and case-control status may have biased the associations between household income and risks of birth defects away from 1. However, this study did not find low household income to be associated with selected birth defects except for a slightly increased risk of TOF. The differential bias shall be minimal, if any. Fourth, the NBDPS data applied the 2000 SOC codes for occupations. Because of the lack of established methods, the 2000 SOC codes had to be converted to the 1990 Census occupation codes to be categorized into SES groups, which may have failed to reflect the occupation changes in the labor force captured in the 2000 SOC codes. Fifth, differential nonparticipation in cases and controls related to SES could have occurred, but we could not examine the possible selection bias because of lack of nonparticipants' data. Sixth, the “unemployed” maternal and paternal occupations include “stay-at-home” parents, which may have a higher household SES level than other unemployment. This study does not have enough data to distinguish them; lumping them together may have failed to uncover some real associations. Last, recall bias is still a potential alternative explanation for the findings, although the recall period in the NBDPS is relatively shorter than that in previous studies.

In summary, this study reveals varied SES-associated risks for specific phenotypes of neural tube defect, orofacial clefts, and conotruncal heart defects. Households at the lowest SES jointly defined by parental education, parental occupation, and household income were at the greatest risk to have all selected birth defects except TOF.

Abbreviations

Abbreviations
 
• AOR

  adjusted odds ratio

 
• CI

  confidence interval

 
• dTGA

  dextrotransposition of the great arteries

 
• NBDPS

  National Birth Defects Prevention Study

 
• SES

  socioeconomic status

 
• SOC

  Standard Occupational Classification

 
• TOF

  tetralogy of Fallot

This research was supported by a cooperative agreement from the Centers for Disease Control and Prevention, Centers of Excellence Award no.U50/CCU913241.

The authors thank Nancy Fleischer for her contribution of coding the occupations using the 1990 Census occupation codes.

The collaborative centers are the Centers for Disease Control and Prevention (CDC), the University of Arkansas for Medical Sciences, Arkansas Children's Hospital in Little Rock, the Iowa Registry for Congenital and Inherited Disorders, the colleges of public health and medicine at the University of Iowa, the California Birth Defects Monitoring Program, the Massachusetts Department of Public Health's Bureau of Family and Community Health, Boston University's Slone Epidemiology Center, Brigham and Women's Hospital's Active Malformation Surveillance Program, the New York Department of Health's Congenital Malformation Registry, the State University of New York School of Public Health, the University of North Carolina School of Public Health at Chapel Hill, the North Carolina Division of Public Health, the Texas Department of State Health Services in Austin, the Texas Birth Defects Registry, the Utah Birth Defect Network, the Utah Department of Health, and the University of Utah Health Sciences Center.

Conflict of interest: none declared.