Abstract
Introduction:
Congenital heart defects, orofacial clefts, and neural tube defects share similar modifiable risk factors. The prevalence and trends of risk factors for these selected birth defects were assessed among nonpregnant, nonlactating women of reproductive age (aged 12–49 years) in the U.S.
Methods:
Cross-sectional data from the National Health and Nutrition Examination Survey 2007–March 2020 were analyzed in fall 2024. Demographics, BMI, household food security, folic acid supplement use, usual intake of dietary folate and vitamin B12, concentrations for serum and red blood cell folate, serum vitamin B12, serum cotinine (smoking exposure), and diabetes status were reported. Weighted percentages of prevalence of risk factors with 95% CIs were calculated using the survey package in R to account for clustered sampling.
Results:
Among 5,374 women of reproductive age, approximately 66.4% (95% CI=64.3, 68.4) had at least 1 known modifiable risk factor: 6.7% (95% CI=5.7, 7.6) reported very low food security, 33.8% (95% CI=32.2, 35.4) had obesity, 4.8% (95% CI=4.0, 5.5) had diabetes, 18.8% (95% CI=17.2, 20.4) had smoking exposure, and 19.5% (95% CI=17.8, 21.1) had red blood cell folate concentrations below the threshold (748 nmol/L) for optimal neural tube defect prevention. Over the time studied, the percentage of women of reproductive age with at least 1 risk factor rose from 65.3% (95% CI=62.1, 68.4) to 69.5% (95% CI=65.4, 73.9; p=0.08).
Conclusions:
Approximately 2 of 3 women of reproductive age in the U.S. have pre-existing modifiable risk factors for birth defects. Implementation of preconception health care could help reduce the prevalence of known risk factors and improve birth outcomes.
INTRODUCTION
Congenital heart defects (CHDs), orofacial clefts (OFCs), and neural tube defects (NTDs) are structural birth defects resulting from abnormalities during embryogenesis that can range in severity.1 These conditions are among some of the most common birth defects, with prevalence of about 100 per 10,000 live births for CHDs; 16 per 10,000 live births for OFCs; and 7 per 10,000 live births for NTDs in the U.S.2–4 The pathogenesis of these birth defects are multifactorial and includes both nonmodifiable and modifiable risk factors. Common modifiable risk factors have been identified through epidemiologic studies, including food insecurity, folate insufficiency, vitamin B12 deficiency, pregestational diabetes mellitus, pregestational obesity, and exposure to cigarette smoke.5–7 In addition, some of these risk factors have been associated with other adverse pregnancy outcomes such as pre-eclampsia, stillbirth, premature birth, and adverse neurodevelopmental outcomes8–10.
These risk factors may contribute to birth defects through the 1-carbon cycle metabolism, a series of pathways essential for cell growth and replication.5 Previous studies have suggested that these risk factors may be attenuated through the consumption of folic acid (FA) periconceptionally and during organogenesis.11 FA intake has been an effective method for decreasing NTD-affected pregnancies.5 Evidence suggests that some CHDs and nonsyndromic OFCs may be reduced through FA consumption.12,13
Understanding the prevalence of selected risk factors among women of reproductive age (WRA) (aged 12–49 years) and their trends can identify opportunities for public health impact. The current analysis estimates the population-level prevalence and trends of selected risk factors among nonpregnant, nonlactating WRA in the U.S.
METHODS
Study Population
The National Health and Nutrition Examination Survey (NHANES) collects cross-sectional data from a nationally representative sample of U.S. civilian, noninstitutionalized population using a stratified, multistage probabilistic design.14 Participants complete household interviews and in-person health examinations at a mobile examination center. In addition, participants respond to 2 dietary-intake 24-hour recall interviews.15 Response rates ranged from 48.8% to 75.4%; detailed survey design and procedures have been described previously.16–21 Analyses combined cross-sectional cycles from NHANES 2007–March 2020 (five 2-year cycles and one 3.2-year prepandemic cycle). Self-reported sex, defined as male or female through questionnaire, and age were used to identify WRA; exclusion criteria included a positive pregnancy test, self-reported pregnancy, or self-reported lactating at the time of interview. Analyses were limited to WRA (aged 12–49 years) with completed dietary recall, red blood cell (RBC) folate, and fasting glucose modules.
Measures
Further information on variable definition, categorization, laboratory procedures, and statistical analysis can be found in Appendix Methods (available online). NHANES data are publicly available deidentified data collected under Human Subject protocols Numbers 2011-17 and 2018-01.
Statistical Analysis
To estimate the percentage of WRA having at least 1 risk factor, 2 risk profiles were developed on the basis of the available risk factors. The all-risks profile included very low household food security, diabetes, prediabetes, obesity, serum cotinine ≥10 ng/mL, and RBC folate concentrations <748 nmol/L. The nonfolate risks profile excluded RBC folate concentration <748 nmol/L. Additional analyses were conducted using only NHANES 2011–March 2020 to assess the prevalence of risk factors among the non-Hispanic Asian (NHA) population owing to oversampling of NHA starting in 2011 and using NHANES 2011–2014 to assess the prevalence of serum vitamin B12 deficiency and insufficiency, which has been associated with NTDs in countries without FA fortification programs.22
RESULTS
NHANES 2007–March 2020 included 5,374 nonpregnant, nonlactating WRA for analysis. Demographics of the sample population and the prevalence of risk factors in the overall population are presented in Table 1.
Table 1.
Demographic Characteristics and Supplementation Use Among U.S. Nonpregnant, Nonlactating Women of Reproductive Age (12–49 Years), NHANES 2007–March 2020
| Population characteristics | Overall | |
|---|---|---|
| n | Weighted % (95% CI) | |
| 5,374 | 100 | |
| Risk factors | ||
| All-risk factors (any)a | 3,690 | 66.4 (64.3, 68.4) |
| None | 1,684 | 33.6 (31.6, 35.7) |
| Nonfolate risk factors (any)b | 3,231 | 59.1 (57.1, 61.2) |
| None | 2,143 | 40.9 (38.8, 42.9) |
| Number of risk factors | ||
| All risk factorsa | ||
| 0 | 1,684 | 33.6 (31.6, 35.7) |
| 1 | 1,812 | 33.2 (31.4, 34.9) |
| 2 | 1,261 | 22.8 (21.3, 24.4) |
| ≥3 | 617 | 10.4 (9.2, 11.5) |
| Nonfolate risk factorb | ||
| 0 | 2,143 | 40.9 (38.8, 42.9) |
| 1 | 1,742 | 32.6 (31.0, 34.3) |
| 2 | 1,122 | 20.2 (18.6, 21.9) |
| ≥3 | 367 | 6.3 (5.4, 7.2) |
| Age, years | ||
| 12–24 | 2,133 | 34.2 (32.4, 36.1) |
| 25–34 | 1,201 | 25.1 (23.2, 27.0) |
| 35–49 | 2,040 | 40.6 (39.0, 42.3) |
| Race/ethnicity | ||
| Non-Hispanic White | 1,801 | 57.8 (54.6, 61.0) |
| Non-Hispanic Black | 1,213 | 13.9 (12.0, 15.7) |
| Hispanic | 1,602 | 19.0 (16.5, 21.4) |
| Other | 758 | 9.3 (8.1, 10.5) |
| Education level | ||
| Less than high school/GED | 1,768 | 25.0 (23.3, 26.7) |
| High school/GED | 813 | 16.2 (14.5, 17.8) |
| More than high school | 2,442 | 53.4 (51.0, 55.7) |
| Do not know/refused/missing | 351 | — |
| Marital statusc | ||
| Married/living with partner | 1,702 | 36.0 (33.9, 38.1) |
| Never married | 827 | 15.5 (13.9, 17.2) |
| Divorced/separated/widowed | 435 | 7.8 (6.7, 8.9) |
| Refused/not reported | 2,410 | — |
| Household income-to-poverty ratio | ||
| <1.0 | 1,437 | 19.5 (17.8, 21.1) |
| 1.0–1.9 | 1,204 | 18.6 (17.0, 20.2) |
| 2.0–3.9 | 1,172 | 25.4 (23.3, 27.5) |
| ≥4.0 | 994 | 27.2 (24.8, 29.6) |
| Missing | 567 | — |
| Household food security | ||
| Full food security | 3,106 | 66.4 (64.3, 68.5) |
| Marginal food security | 800 | 12.2 (11.0, 13.4) |
| Low food security | 895 | 13.0 (11.8, 14.2) |
| Very low food securityd | 470 | 6.7 (5.7, 7.6) |
| Missing | 103 | — |
| Folic acid–containing supplements | ||
| Any | 1,302 | 28.0 (26.3, 29.7) |
| ≥400 mcg/day | 579 | 12.6 (11.3, 14.0) |
| None | 4,071 | 72.0 (70.3, 73.7) |
| Missing | 1 | — |
| Folic acid consumption group | ||
| ECGP/CMF only | 2,994 | 53.6 (51.9, 55.2) |
| ECGP/CMF + RTE | 1,077 | 18.4 (17.1, 19.7) |
| ECGP/CMF + SUPP | 964 | 20.2 (18.9, 21.6) |
| ECGP/CMF + RTE + SUPP | 338 | 7.8 (6.7, 8.8) |
| Missing | 1 | — |
| Usual intakee | ||
| Total folic acid (mcg/day): median (IQR) | 5,259 | 166 (107, 314) |
| % intake <400 mcg/day | 4,378 | 79.7 (77.9, 81.5) |
| Dietary folic acid (excluding supplement, mcg/day): median (IQR): | 5,259 | 146 (101, 204) |
| % intake <400 mcg/day (excluding supplement) | 5,199 | 98.7 (98.7, 98.9) |
| BMIf | ||
| Underweight | 273 | 4.7 (4.0, 5.5) |
| Healthy weight | 1,879 | 36.9 (35.0, 38.9) |
| Overweight | 1,287 | 23.5 (22.0, 24.9) |
| Obesityd | 1,861 | 33.8 (32.2, 35.4) |
| Missing | 74 | — |
| Serum cotinine, ng/mL | ||
| ≥10d | 946 | 18.8 (17.2, 20.4) |
| <10 | 4,377 | 80.3 (78.8, 81.8) |
| Missing | 51 | — |
| Diabetesg | ||
| Yesd | 307 | 4.8 (4.0, 5.5) |
| Yes, diagnosed | 202 | 3.2 (2.6, 3.8)h |
| Yes, diagnosed, controlled | 75 | 1.3 (1.0, 1.7)h |
| Yes, diagnosed, uncontrolled | 127 | 1.9 (1.4, 2.3)h |
| Yes, undiagnosed | 105 | 1.6 (1.2, 1.9)h |
| Prediabetesd | 1,586 | 28.9 (27.1, 30.8) |
| No | 3,472 | 66.1 (64.0, 68.2) |
| Missing | 9 | — |
| RBC folate concentrations | ||
| Low (<748 nmol/L)d | 1,194 | 19.5 (17.8, 21.1) |
| Adequate (≥748 nmol/L) | 4,149 | 80.1 (78.5, 81.7) |
| Missing | 31 | — |
Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity, and RBC folate concentrations <748 nmol/L.
Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity.
Marital status only asked to those aged >20 years; WRA aged ≤20 were categorized as refused/not reported.
Category counting toward total number of risk factors for individuals.
Analysis conducted on the pseudo-person level utilizing 2-day dietary data (each participant generated 100 pseudo-persons with 1/100 the weight of the participant).
BMI categories were defined as underweight (BMI<18.5), healthy weight (18.5≤BMI<25), overweight (25≤BMI<30), and obesity (BMI≥30); NHA participants had BMI categories defined as underweight (BMI<18.5), healthy weight (18.5≤BMI<23), overweight (23≤BMI<27.5), and obesity (BMI≥27.5).
Diabetes diagnosis is defined as yes (diagnosed) by self-identification on a questionnaire or yes (undiagnosed) if not indicated on questionnaire and having HbA1c ≥6.5% or fasting blood glucose ≥126 mg/dL, prediabetes is defined as having either HbA1c=5.7%–6.5% or fasting blood glucose=100–125 mg/dL, and no is defined as having HbA1c <5.7% and fasting blood glucose <100 mg/dL.
Cell has <8 degrees of freedom.
CMF, corn masa flour; ECGP, enriched cereal grain product; NHA, non-Hispanic Asian; NHANES, National Health and Nutrition Survey Examination; RBC, red blood cell; RTE, ready-to-eat cereal; SUPP, folic acid containing supplement.
Overall, approximately 66.4% (95% CI=64.3, 68.4) (Table 1) of WRA had at least 1 known risk factor, with 10.4% (95% CI=9.2, 11.5) having had 3 or more known risk factors using the all-risks profile. With the nonfolate risks profile, 59.1% (95% CI=57.1, 61.2) had at least 1 known risk factor, and 6.3% (95% CI=5.4, 7.2) had 3 or more known risk factors.
Very low food security was reported in 6.7% (95% CI=5.7, 7.6) (Table 1) of WRA. Approximately 28.0% (95% CI=26.3, 29.7) of WRA reported consuming FA-containing supplements, and 27.2% (95% CI=25.5, 28.9) consumed supplements containing both FA and vitamin B12. Only 12.6% (95% CI=11.3, 14.0) of WRA consumed supplements that had ≥400 μg/day of FA. When analyzing estimated usual FA intakes when excluding supplement use, 98.7% (95% CI=98.7, 98.9) had intakes <400 μg/day, and 79.7% (95% CI=77.9, 81.5) still had FA usual intakes <400 μg/day including supplement use. Approximately 19.5% (95% CI=17.8, 21.1) of WRA had RBC folate concentrations <748 nmol/L.
Approximately 33.8% (95% CI=32.2, 35.4) (Table 1) of WRA had obesity. Serum cotinine levels were ≥10 ng/mL in 18.8% (95% CI=17.2, 20.4) of WRA. Approximately 4.8% (95% CI=4.0, 5.5) had diabetes, and 28.9% (95% CI=27.1, 30.8) had prediabetes.
Using the all-risks profile, the percentage of WRA with at least 1 known risk factor had a trending increase over time from 65.3% (95% CI=62.1, 68.4) in 2007–2010 to 69.5% (95% CI=65.4, 73.6) in 2015–2020 (p=0.079) (Table 2). There was a statistically significant increase of WRA with at least 1 nonfolate risk over time from 55.3% (95% CI=52.2, 58.3) in 2007–2010 to 64.0% (95% CI=59.8, 68.1) in 2015–2020 (p=0.003) (Table 2). The prevalence of RBC folate concentrations <748 nmol/L decreased from 23.4% (95% CI=20.3, 26.5) to 17.9% (95% CI=15.2, 20.7; p=0.012).
Table 2.
Prevalence of Risk Factors for Selected Birth Defects Among U.S. Nonpregnant, Nonlactating Women of Reproductive Age by NHANES Survey Cycle
| Population characteristics | 2007–2010 | 2011–2014 | 2015–Mar 2020 | p valuea | |||
|---|---|---|---|---|---|---|---|
| n | Weighted % (95% CI) | n | Weighted % (95% CI) | n | Weighted % (95% CI) | ||
| 1,689 | 1,728 | 1,957 | |||||
| Number of risk factors | |||||||
| All-risk factors (any)b | 1,162 | 65.3 (62.1, 68.4) | 1,119 | 63.4 (60.1, 66.7) | 1,409 | 69.5 (65.4, 73.6) | 0.079 |
| None | 527 | 34.7 (31.6, 37.9) | 609 | 36.6 (33.3, 39.9) | 548 | 30.5 (26.4, 34.6) | 0.079 |
| Nonfolate risk factors (any)c | 980 | 55.3 (52.2, 58.3) | 969 | 56.7 (53.6, 59.8) | 1282 | 64.0 (59.8, 68.1) | 0.0008 |
| None | 709 | 44.7 (41.7, 47.8) | 759 | 43.3 (40.2, 46.4) | 675 | 36.0 (31.9, 40.2) | 0.0008 |
| Household food security | |||||||
| Full food security | 1,040 | 73.4 (70.2, 76.6) | 1,020 | 64.7 (60.5, 68.9) | 1,046 | 62.4 (58.7, 66.0) | 0.0001 |
| Marginal food security | 236 | 9.4 (7.3, 11.5) | 274 | 14.0 (11.6, 16.4) | 290 | 12.9 (11.1, 14.7) | 0.015 |
| Low food security | 265 | 11.3 (9.4, 13.2) | 273 | 13.1 (11.1, 15.2) | 357 | 14.2 (11.9, 16.5) | 0.035 |
| Very low food securityd | 129 | 5.0 (3.5, 6.5) | 148 | 7.0 (5.2, 8.9) | 193 | 7.6 (6.0, 9.3) | 0.016 |
| Missing | 19 | — | 13 | — | 71 | — | |
| Folic acid containing supplements | |||||||
| Any | 419 | 30.0 (26.6, 33.4) | 421 | 27.1 (24.7, 29.6) | 462 | 27.1 (23.9, 30.2) | 0.22 |
| ≥400 mcg/day | 201 | 14.9 (12.1, 17.6) | 184 | 12.2 (9.8, 14.6) | 194 | 11.3 (9.1, 13.4) | 0.043 |
| None | 1,269 | 70.0 (66.6, 73.4) | 1,307 | 72.9 (70.4, 75.3) | 1,495 | 72.9 (69.8, 76.1) | 0.22 |
| Missing | 1 | — | — | — | — | — | |
| Folic acid consumption group | |||||||
| ECGP/CMF only | 890 | 49.4 (46.0, 52.9) | 939 | 52.8 (49.8, 55.8) | 1165 | 57.3 (54.8, 59.9) | 0.0003 |
| ECGP/CMF + RTE | 379 | 20.4 (18.3, 22.5) | 368 | 20.0 (17.3, 22.8) | 330 | 15.6 (13.5, 17.6) | 0.0009 |
| ECGP/CMF + SUPP | 273 | 18.9 (16.7, 21.1) | 318 | 20.3 (18.1, 22.4) | 373 | 21.2 (18.6, 23.7) | 0.19 |
| ECGP/CMF + RTE + SUPP | 146 | 11.1 (8.4, 13.8) | 103 | 6.9 (5.3, 8.5) | 89 | 5.9 (4.5, 7.3) | 0.0005 |
| Missing | 1 | — | — | — | — | — | |
| Usual intakee | |||||||
| Total folic acid (mcg/day): median (IQR) | 1,628 | 172 (110, 349) | 1,674 | 166 (107, 307) | 1,957 | 161 (104, 295) | |
| % intake <400 mcg/day | 1,333 | 77.6 (75.1, 80.2) | 1,396 | 80.3 (77.5, 83.0) | 1,649 | 80.9 (77.3, 84.5) | 0.16 |
| Dietary folic acid (excluding supplement mcg/day): median (IQR): | 1,628 | 148 (103, 207) | 1,674 | 146 (101, 203) | 1,957 | 143 (99, 201) | |
| % intake <400 mcg/day (excluding supplement) | 1,607 | 98.5 (98.4, 98.7) | 1,655 | 98.7 (98.6, 98.9) | 1,938 | 98.9 (98.7, 99.0) | 0.003 |
| BMIf | |||||||
| Underweight | 85 | 4.9 (3.6, 6.1) | 93 | 4.4 (3.3, 5.6) | 95 | 4.9 (3.4, 6.3) | 0.98 |
| Healthy weight | 629 | 41.0 (38.3, 43.7) | 640 | 37.5 (33.8, 41.3) | 610 | 33.3 (29.7, 36.9) | 0.0008 |
| Overweight | 429 | 24.2 (21.7, 26.6) | 399 | 23.2 (20.7, 25.7) | 459 | 23.1 (20.6, 25.7) | 0.53 |
| Obesityd | 525 | 28.9 (26.3, 31.5) | 568 | 33.5 (31.2, 35.8) | 768 | 37.9 (34.8, 40.9) | <0.0001 |
| Missing | 21 | — | 28 | — | 25 | — | |
| Diabetesg | |||||||
| Yesd | 75 | 3.2 (2.3, 4.1) | 89 | 4.6 (3.5, 5.7) | 143 | 6.0 (4.6, 7.5) | 0.001 |
| Diagnosed | 49 | 2.3 (1.5, 3.1) | 59 | 3.2 (2.3, 4.1) | 94 | 3.9 (2.7, 5.1) | 0.023 |
| Controlled (HbA1c <6.5) | 19 | 1.0 (0.5, 1.5)h | 21 | 1.0 (0.4, 1.6)h | 35 | 1.8 (1.1, 2.6)i | 0.063 |
| Uncontrolled (HbA1c ≥6.5) | 30 | 1.3 (0.7, 1.8)h | 38 | 2.2 (1.4, 2.9) | 59 | 2.0 (1.2, 2.8)i | 0.13 |
| Undiagnosed | 26 | 0.9 (0.4, 1.4)h | 30 | 1.4 (0.9, 2.0)i | 49 | 2.2 (1.4, 2.9) | 0.007 |
| Prediabetesd | 480 | 26.5 (23.4, 29.6) | 422 | 24.0 (21.1, 26.8) | 684 | 34.6 (31.1, 38.1) | 0.0003 |
| No | 1,129 | 70.0 (66.5, 73.6) | 1,216 | 71.4 (67.9, 74.9) | 1,127 | 59.0 (55.4, 62.7) | <0.0001 |
| Missing | 5 | — | 1 | — | 3 | — | |
| Serum cotinine, ng/mL | |||||||
| ≥10g | 344 | 21.2 (18.1, 24.2) | 286 | 19.0 (16.6, 21.4) | 316 | 16.8 (14.1, 19.5) | <0.0001 |
| <10 | 1,335 | 78.4 (75.4, 81.4) | 1,423 | 80.2 (77.8, 82.7) | 1,619 | 81.8 (79.1, 84.5) | <0.0001 |
| Missing | 10 | — | 19 | — | 22 | — | |
| RBC folate concentrations | |||||||
| Low (<748 nmol/L)d | 436 | 23.4 (20.3, 26.5) | 351 | 17.5 (14.9, 20.1) | 407 | 17.9 (15.2, 20.7) | 0.012 |
| Adequate (≥748 nmol/L) | 1,247 | 76.4 (73.4, 79.4) | 1,362 | 81.7 (79.0, 84.3) | 1,540 | 81.7 (78.9, 84.4) | 0.012 |
| Missing | 6 | — | 15 | — | 10 | — | |
Note: Boldface indicates statistical significance (p<0.05).
p-values calculated using a trend test.
Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity, and RBC folate concentrations <748 nmol/L.
Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, and obesity.
Analysis conducted on the pseudo-person level utilizing 2-day dietary data (each participant generated 100 pseudo-persons with 1/100 the weight of the participant).
BMI categories were defined as underweight (BMI<18.5), healthy weight (18.5≤BMI<25), overweight (25≤BMI<30), and obesity (BMI≥30); NHA participants had BMI categories defined as underweight (BMI<18.5), healthy weight (18.5≤BMI<23), overweight (23≤BMI<27.5), and obesity (BMI≥27.5).
Diabetes diagnosis is defined as yes (diagnosed) by self-identification on a questionnaire and yes (undiagnosed) if not indicated on questionnaire and having HbA1c ≥6.5% or fasting blood glucose ≥126 mg/dL, prediabetes is defined as having either HbA1c=5.7%–6.5% or fasting blood glucose=100–125 mg/dL, and no is defined as having HbA1c <5.7% and fasting blood glucose <100 mg/dL.
Category counting toward total number of risk factors for individuals.
Cell has <8 degrees of freedom and a sample size <30.
Cell has <8 degrees of freedom.
CMF, corn masa flour; ECGP, enriched cereal grain product; NHA, non-Hispanic Asian; NHANES, National Health and Nutrition Survey Examination; RBC, red blood cell; RTE, ready-to-eat cereal; SUPP, folic acid containing supplement.
An increase in very low food security was observed (p=0.016) (Table 2). Overall, consumption of FA-containing supplements did not show significant change over time (p=0.22), whereas consumption of supplements containing ≥400 μg/day FA decreased from 14.9% (95% CI=12.1, 17.6) in 2007–2010 to 11.3% (95% CI=9.1, 13.4; p=0.043) in 2015–March 2020. The percentage of WRA with total FA intake <400 μg/day slightly increased from 77.6% (95% CI=75.1, 80.2) to 80.9% (95% CI=77.3, 84.5; p=0.16).
Obesity prevalence increased over time from 28.9% (95% CI=26.3, 31.5) to 37.9% (95% CI=34.8, 40.9; p<0.0001) (Table 3). Diabetes prevalence also increased from 3.2% (95% CI=2.3, 4.1) to 6.0% (95% CI=4.6, 7.5; p=0.001), with a significant increase among both diagnosed (p=0.023) and undiagnosed (p=0.007) diabetes. WRA with prediabetes also increased from 26.5% (95% CI=23.4, 29.6) to 34.6% (95% CI=31.1, 38.1; p=0.0003). Serum cotinine concentrations associated with active tobacco use decreased from 21.2% (95% CI=18.1, 24.2) to 16.8% (95% CI=14.1, 19.5; p<0.0001).
Table 3.
Prevalence of Risk Factors for Selected Birth Defects Among U.S. Nonpregnant, Nonlactating Women of Reproductive Age by Age Group, NHANES 2007–March 2020
| Population characteristics | 12–24 years | 25–34 years | 35–49 years | p-valuea | |||
|---|---|---|---|---|---|---|---|
| n | Weighted % (95% CI) | n | Weighted % (95% CI) | n | Weighted % (95% CI) | ||
| 2,133 | 1,201 | 2,040 | |||||
| Risk factors | |||||||
| All-risk factors (any)b | 1,251 | 55.9 (52.5, 59.4) | 860 | 68.7 (65.1, 72.2) | 1,579 | 73.7 (71.4, 76.0) | <0.0001 |
| None | 882 | 44.1 (40.6, 47.5) | 341 | 31.3 (27.8, 34.9) | 461 | 26.3 (24.0, 28.6) | <0.0001 |
| Nonfolate risk factors (any)c | 973 | 44.6 (41.3, 47.8) | 761 | 61.8 (58.4, 65.2) | 1,497 | 69.8 (67.3, 72.4) | <0.0001 |
| None | 1,160 | 55.4 (52.2, 58.7) | 440 | 38.2 (34.8, 41.6) | 543 | 30.2 (27.6, 32.7) | <0.0001 |
| Household food security | |||||||
| Full food security | 1,187 | 65.1 (61.8, 68.4) | 671 | 62.6 (58.3, 66.8) | 1,248 | 69.9 (67.3, 72.6) | 0.004 |
| Marginal food security | 326 | 11.7 (9.9, 13.4) | 212 | 16.2 (13.6, 18.8) | 262 | 10.1 (8.6, 11.7) | 0.085 |
| Low food security | 379 | 13.6 (11.5, 15.8) | 204 | 13.9 (11.4, 16.3) | 312 | 11.9 (10.4, 13.5) | 0.092 |
| Very low food securityd | 198 | 7.5 (6.0, 9.0) | 94 | 5.7 (4.4, 7.1) | 178 | 6.5 (5.3, 7.7) | 0.24 |
| Missing | 43 | — | 20 | — | 40 | — | |
| Folic acid containing supplements | |||||||
| Any | 342 | 18.6 (15.9, 21.3) | 325 | 30.3 (26.9, 33.8) | 635 | 34.4 (31.9, 37.0) | <0.0001 |
| ≥400 mcg/day | 93 | 5.3 (3.8, 6.8) | 151 | 14.1 (11.4, 16.9) | 335 | 17.9 (15.6, 20.2) | <0.0001 |
| None | 1,790 | 81.4 (78.7, 84.1) | 876 | 69.7 (66.2, 73.1) | 1,405 | 65.6 (63.0, 68.1) | <0.0001 |
| Missing | 1 | — | — | — | — | — | |
| Folic acid consumption group | |||||||
| ECGP/CMF only | 1,200 | 55.2 (52.5, 57.9) | 662 | 52.7 (48.9, 56.4) | 1,132 | 52.8 (50.1, 55.5) | 0.22 |
| ECGP/CMF + RTE | 590 | 26.0 (23.5, 28.6) | 214 | 17.0 (14.3, 19.7) | 273 | 12.8 (11.0, 14.5) | <0.0001 |
| ECGP/CMF + SUPP | 220 | 12.3 (10.2, 14.4) | 264 | 24.4 (21.6, 27.2) | 480 | 24.3 (22.0, 26.7) | <0.0001 |
| ECGP/CMF + RTE + SUPP | 1,22 | 6.3 (4.8, 7.9) | 61 | 6.0 (4.1, 7.8) | 155 | 10.1 (8.3, 11.9) | 0.002 |
| Missing | 1 | — | — | — | — | — | |
| Usual Intakee | |||||||
| Total folic acid (mcg/day): median (IQR) | 2,101 | 153 (102, 240) | 1,176 | 169 (108, 327) | 1,982 | 178 (111, 437) | |
| % intake <400 mcg/day | 1,909 | 88.3 (86.1, 90.5) | 955 | 78.9 (75.5, 82.3) | 1,514 | 73.3 (70.5, 76.1) | <0.0001 |
| Dietary folic acid (excluding supplement; mcg/day): median (IQR): | 2,101 | 142 (99, 199) | 1,176 | 146 (101, 203) | 1,982 | 148 (103, 207) | |
| % intake <400 mcg/day (excluding supplement) | 2,080 | 98.9 (98.9, 99.1) | 1,163 | 98.8 (98.7, 99.0) | 1,956 | 98.5 (98.4, 98.7) | <0.0001 |
| BMIf | |||||||
| Underweight | 201 | 9.3 (7.8, 10.9) | 42 | 3.5 (2.0, 5.0)i | 30 | 1.6 (0.9, 2.3)‡ | <0.0001 |
| Healthy weight | 994 | 48.2 (45.1, 51.4) | 381 | 33.9 (30.2, 37.6) | 504 | 29.2 (26.5, 32.0) | <0.0001 |
| Overweight | 437 | 19.4 (17.4, 21.5) | 292 | 23.2 (20.4, 26.0) | 558 | 27.0 (24.5, 29.5) | <0.0001 |
| Obesityd | 462 | 21.6 (19.1, 24.0) | 479 | 39.0 (35.4, 42.6) | 920 | 41.0 (38.3, 43.7) | <0.0001 |
| Missing | 39 | — | 7 | — | 28 | — | |
| Serum cotinine, ng/mL | |||||||
| ≥10g | 224 | 11.9 (10.0, 13.7) | 271 | 21.9 (19.5, 24.3) | 451 | 22.7 (19.9, 25.6) | <0.0001 |
| <10 | 1,883 | 87.1 (85.2, 89.0) | 921 | 77.4 (75.0, 79.8) | 1,573 | 76.3 (73.3, 79.3) | <0.0001 |
| Missing | 26 | — | 9 | — | 16 | — | |
| Diabetesg | |||||||
| Yesg | 21 | 0.7 (0.4, 1.0)h | 42 | 3.0 (1.8, 4.2)i | 244 | 9.3 (7.7, 10.8) | <0.0001 |
| Yes, diagnosed | 15 | 0.6 (0.3, 0.9)h | 23 | 1.8 (0.9, 2.8)h | 164 | 6.2 (4.9, 7.6) | <0.0001 |
| Yes, diagnosed, controlled | 8 | 0.4 (0.1, 0.7)h,j | 6 | 0.5 (0.1, 0.9)h | 61 | 2.7 (1.8, 3.5)i | <0.0001 |
| Yes, diagnosed, uncontrolled | 7 | 0.2 (0.0, 0.3)h,j | 17 | 1.4 (0.5, 2.2)h,j | 103 | 3.6 (2.7, 4.5) | <0.0001 |
| Yes, undiagnosed | 6 | 0.1 (0.0, 0.3)h,j | 19 | 1.2 (0.5, 1.9)h,j | 80 | 3.0 (2.2, 3.8) | <0.0001 |
| Prediabetesd | 444 | 19.0 (16.6, 21.4) | 364 | 28.4 (24.9, 31.9) | 778 | 37.6 (34.8, 40.4) | <0.0001 |
| No | 1,667 | 80.3 (77.8, 82.8) | 791 | 68.0 (64.4, 71.7) | 1,014 | 52.9 (50.0, 55.8) | <0.0001 |
| Missing | 1 | — | 4 | — | 4 | — | |
| RBC folate concentrations | |||||||
| Low (<748 nmol/L)d | 526 | 22.1 (19.4, 24.8) | 303 | 20.9 (18.0, 23.9) | 365 | 16.3 (14.2, 18.5) | 0.0006 |
| Adequate (≥748 nmol/L) | 1,599 | 77.6 (74.9, 80.2) | 895 | 78.9 (76.0, 81.8) | 1,655 | 82.9 (80.8, 85.1) | 0.0006 |
| Missing | 8 | — | 3 | — | 20 | — | |
Note: Boldface indicates statistical significance (p<0.05).
p-values calculated using trend analysis.
Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity, and RBC folate concentrations <748 nmol/L.
Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, and obesity.
Category counting toward total number of risk factors for individuals.
Analysis conducted on the pseudo-person level utilizing 2-day dietary data (each participant generated 100 pseudo-persons with 1/100 the weight of the participant).
BMI categories were defined as underweight (BMI<18.5), healthy weight (18.5≤BMI<25), overweight (25≤BMI<30), and obesity (BMI≥30); NHA participants had BMI categories defined as underweight (BMI<18.5), healthy weight (18.5≤BMI<23), overweight (23≤BMI<27.5), and obesity (BMI≥27.5).
Diabetes diagnosis is defined as yes (diagnosed) by self-identification on a questionnaire and yes (undiagnosed) if not indicated on questionnaire and having HbA1C ≥6.5% or fasting blood glucose ≥126 mg/dL, prediabetes is defined as having either HbA1C=5.7%–6.5% or fasting blood glucose=100–125 mg/dL, and no is defined as having HbA1c <5.7% and fasting blood glucose <100 mg/dL.
Cell has <8 degrees of freedom and a sample size <30.
Cell has <8 degrees of freedom.
Does not meet the criteria for prevalence estimate reliability.
CMF, corn masa flour; ECGP, enriched cereal grain product; NHA, non-Hispanic Asian; NHANES, National Health and Nutrition Survey Examination; RBC, red blood cell; RTE, ready-to-eat cereal; SUPP, folic acid containing supplement.
For the all-risks profile, the proportion of WRA with least 1 risk factor increased with age from 55.9% (95% CI=52.5, 59.4) up to 73.7% (95% CI=71.4, 76.0; p<0.0001) (Table 3). A similar trend was seen in the nonfolate risks profile, increasing from 44.6% (95% CI=41.3, 47.8) to 69.8% (95% CI=67.3, 72.4; p<0.0001).
The prevalence of very low food security was similarly reported across age groups (p=0.24) (Table 3). Use of FA-containing supplements increased from 18.6% (95% CI=15.9, 21.3) among those aged 12–24 years to 34.4% (95% CI=31.9, 37.0) among those aged 35–49 years (p<0.0001). A similar trend was found with supplements containing ≥400 μg/day FA (those aged 12–24 years: 5.3% [95% CI=3.8, 6.8]; those aged 35–49 years: 17.9% [95% CI=15.6, 20.2]; p<0.0001). Consumption of total FA usual intake <400 μg/day, including supplements, decreased from 88.3% (95% CI=86.1, 90.5) among those aged 12–24 years to 73.3% (95% CI=70.5, 76.1) among those aged 35–49 years (p<0.0001). The prevalence of RBC folate concentrations <748 nmol/L decreased from 22.1% (95% CI=19.4, 24.8) among those aged 12–24 years to 16.3% among those aged 35–49 years (95% CI=14.2, 18.5; p=0.0006).
Prevalence of obesity increased with age from 21.6% (95% CI=19.1, 24.0) to 41.0% (95% CI=38.3, 43.7; p<0.0001) (Table 3). Prevalence of diabetes similarly increased with age up to 9.3% (95% CI=7.7, 10.8; p<0.0001) among WRA aged 35–49 years. Elevated serum cotinine concentrations increased with age up to 22.7% (95% CI=19.9, 25.6; p<0.0001) (Table 3) among those aged 35–49 years.
There was a significant difference in the percentage of women with at least 1 risk factor by race and ethnic group in both the all-risks profile (non-Hispanic White [NHW]: 62.2% [95% CI=58.9, 65.4]; non-Hispanic Black [NHB]: 80.4% [95% CI=77.8, 83.0]; Hispanic: 70.0% [95% CI=67.0, 73.0]; non-Hispanic other [NHO[: 64.2% [95% CI=59.9, 69.6]; p<0.0001) (Table 4) and the nonfolate risks profile (NHW: 56.2% [95% CI=52.9, 59.4]; NHB: 70.3% [95% CI=67.5, 73.2]; Hispanic: 62.8% [95% CI=59.7, 65.8]; NHO: 53.6% [95% CI=48.4, 58.9]; p<0.0001).
Table 4.
Prevalence of Risk Factors for Selected Birth Defects Among U.S. Nonpregnant, Nonlactating Women of Reproductive Age by Race/Ethnicity, NHANES 2007–March 2020
| Population characteristics | Non-Hispanic White | Non-Hispanic Black | Hispanic | Non-hispanic other | p-valuea | ||||
|---|---|---|---|---|---|---|---|---|---|
| n | Weighted % (95% CI) | n | Weighted % (95% CI) | n | Weighted % (95% CI) | n | Weighted % (95% CI) | ||
| 1,801 | 1,213 | 1,602 | 758 | ||||||
| Risk factors | |||||||||
| All-risk factors (any)b | 1,177 | 62.2 (58.9, 65.4) | 961 | 80.4 (77.8, 83.0) | 1,087 | 70.0 (67.0, 73.0) | 465 | 64.2 (59.9, 69.6) | <0.0001 |
| None | 624 | 37.8 (34.6, 41.1) | 252 | 19.6 (17.0, 22.2) | 515 | 30.0 (27.0, 33.0) | 293 | 35.8 (30.4, 41.2) | <0.0001 |
| Nonfolate risk factors (any)c | 1,075 | 56.2 (52.9, 59.4) | 831 | 70.3 (67.5, 73.2) | 953 | 62.8 (59.7, 65.8) | 372 | 53.6 (48.4, 58.9) | <0.0001 |
| None | 726 | 43.8 (40.6, 47.1) | 382 | 29.7 (26.8, 32.5) | 649 | 37.2 (34.2, 40.3) | 386 | 46.4 (41.1, 51.6) | <0.0001 |
| Household food security | |||||||||
| Full food security | 1,222 | 75.5 (72.7, 78.2) | 578 | 50.6 (46.5, 54.6) | 773 | 48.7 (44.8, 52.6) | 533 | 69.8 (64.7, 74.9) | <0.0001 |
| Marginal food security | 183 | 8.6 (6.9, 10.2) | 212 | 17.5 (14.2, 20.7) | 310 | 19.0 (16.6, 21.4) | 95 | 12.8 (9.3, 16.4) | <0.0001 |
| Low food security | 222 | 9.3 (7.8, 10.8) | 269 | 20.3 (17.3, 23.4) | 340 | 21.0 (18.6, 23.4) | 64 | 8.5 (5.9, 11.2) | <0.0001 |
| Very low food securityd | 153 | 5.4 (4.3, 6.5) | 133 | 10.0 (7.2, 12.7) | 143 | 8.6 (6.6, 10.5) | 41 | 5.7 (2.9, 8.5)h | 0.004 |
| Missing | 21 | — | 21 | — | 36 | — | 25 | — | |
| Folic acid supplements | |||||||||
| Any | 531 | 31.5 (29.1, 33.9) | 241 | 21.6 (18.6, 24.7) | 331 | 22.0 (19.4, 24.5) | 199 | 27.9 (23.5, 32.4) | <0.0001 |
| ≥400 mcg/day | 251 | 14.5 (12.6, 16.5) | 99 | 9.0 (6.8, 11.1) | 148 | 9.7 (7.9, 11.5) | 81 | 12.4 (8.9, 16.0) | 0.0002 |
| None | 1,270 | 68.5 (66.1, 70.9) | 972 | 78.4 (75.3, 81.4) | 1,271 | 78.0 (75.5, 80.6) | 558 | 72.1 (67.6, 76.5) | <0.0001 |
| Missing | — | — | — | — | — | — | 1 | — | |
| Folic acid consumption group | |||||||||
| ECGP/CMF only | 904 | 50.3 (47.8, 52.8) | 726 | 59.0 (55.6, 62.4) | 904 | 57.0 (54.3, 59.7) | 460 | 58.9 (53.9, 63.9) | <0.0001 |
| ECGP/CMF + RTE | 366 | 18.2 (16.1, 20.3) | 246 | 19.3 (16.5, 22.2) | 367 | 21.0 (18.6, 23.4) | 98 | 12.6 (9.6, 15.6) | 0.001 |
| ECGP/CMF + SUPP | 373 | 21.7 (19.9, 23.6) | 187 | 17.0 (14.3, 19.7) | 244 | 16.8 (14.6, 19.0) | 160 | 22.7 (18.3, 27.1) | 0.0004 |
| ECGP/CMF + RTE + SUPP | 158 | 9.8 (8.1, 11.4) | 54 | 4.7 (3.2, 6.1)h | 87 | 5.2 (4.1, 6.3) | 39 | 5.2 (3.0, 7.5) | <0.0001 |
| Missing | — | — | — | — | — | — | 1 | — | |
| Usual intakee | |||||||||
| Total folic acid (mcg/day): median (IQR) | 1,775 | 174 (110, 371) | 1,185 | 153 (102, 249) | 1,563 | 156 (103, 256) | 736 | 162 (104, 294) | |
| % intake <400 mcg/day | 1,393 | 76.5 (74.0, 78.9) | 1,028 | 85.8 (83.0, 88.7) | 1,346 | 84.6 (81.8, 87.3) | 612 | 81.1 (76.9, 85.4) | <0.0001 |
| Dietary folic acid (excluding supplement mcg/day): median (IQR): | 1,775 | 148 (103, 208) | 1,185 | 141 (98, 186) | 1,563 | 143 (99, 199) | 736 | 142 (99, 199) | |
| % intake <400 mcg/day (excluding supplement) | 1,751 | 98.6 (98.5, 98.7) | 1,174 | 99.0 (98.9, 99.1) | 1,546 | 98.9 (98.8, 99.1) | 728 | 98.8 (98.6, 99.0) | <0.0001 |
| BMIf | |||||||||
| Underweight | 92 | 5.0 (3.9, 6.2) | 46 | 3.4 (2.2, 4.5)‡ | 69 | 3.6 (2.6, 4.5)‡ | 66 | 7.1 (4.9, 9.4)‡ | 0.015 |
| Healthy weight | 721 | 41.1 (38.0, 44.2) | 324 | 25.0 (22.3, 27.6) | 503 | 29.4 (27.1, 31.7) | 331 | 43.7 (38.3, 49.2) | <0.0001 |
| Overweight | 399 | 22.8 (20.6, 24.9) | 270 | 22.9 (20.7, 25.1) | 445 | 27.1 (24.5, 29.6) | 173 | 21.3 (17.1, 25.4) | 0.015 |
| Obesityg | 570 | 30.3 (27.7, 32.8) | 554 | 47.4 (44.4, 50.4) | 557 | 38.2 (35.7, 40.7) | 180 | 27.0 (21.8, 32.1) | <0.0001 |
| Missing | 19 | — | 19 | — | 28 | — | 8 | — | |
| Serum cotinine | |||||||||
| ≥10 ng/mL | 466 | 21.7 (19.3, 24.1) | 271 | 23.4 (19.9, 26.8) | 119 | 7.7 (6.0, 9.5) | 90 | 16.5 (12.0, 21.0) | <0.0001 |
| <10 ng/mL | 1,321 | 77.5 (75.2, 79.8) | 925 | 75.2 (71.5, 78.9) | 1,471 | 91.5 (89.6, 93.3) | 660 | 82.2 (77.7, 86.8) | <0.0001 |
| Missing | 14 | — | 17 | — | 12 | — | 8 | — | |
| Diabetesg | |||||||||
| Yesg | 77 | 3.4 (2.4, 4.3) | 88 | 6.7 (5.2, 8.3) | 108 | 7.4 (5.9, 8.9) | 34 | 5.0 (3.0, 7.0) | <0.0001 |
| Yes, diagnosed | 50 | 2.4 (1.5, 3.2)h | 61 | 4.7 (3.6, 5.9) | 69 | 4.8 (3.5, 6.1) | 22 | 2.8 (1.4, 4.2)i | 0.001 |
| Yes, diagnosed, controlled | 19 | 1.0 (0.5, 1.6)i,j | 17 | 1.4 (0.7, 2.1)i | 27 | 2.0 (1.2, 2.8)i | 12 | 1.6 (0.6, 2.7)i | 0.24 |
| Yes, diagnosed, uncontrolled | 31 | 1.3 (0.8, 1.9)h | 44 | 3.3 (2.3, 4.3)h | 42 | 2.8 (1.9, 3.7)h | 10 | 1.1 (0.2, 2.1)i,j | 0.0003 |
| Yes, undiagnosed | 27 | 1.0 (0.5, 1.5)i | 27 | 2.0 (1.1, 3.0) | 39 | 2.6 (1.8, 3.4)h | 12 | 2.2 (0.8, 3.6)i,j | 0.012 |
| Prediabetesd | 472 | 26.3 (23.6, 29.0) | 387 | 32.9 (29.7, 36.1) | 500 | 32.5 (29.1, 35.9) | 227 | 32.1 (26.7, 37.5) | 0.003 |
| No | 1,250 | 70.1 (67.2, 73.1) | 734 | 60.0 (56.9, 63.1) | 992 | 60.0 (56.8, 63.1) | 496 | 62.6 (57.4, 67.7) | <0.0001 |
| Missing | 2 | — | 4 | — | 2 | — | 1 | — | |
| RBC folate concentrations | |||||||||
| Low (<748 nmol/L)d | 297 | 15.9 (13.6, 18.1) | 418 | 35.0 (32.1, 38.0) | 305 | 18.3 (16.1, 20.5) | 174 | 20.8 (17.4, 24.3) | <0.0001 |
| Adequate (≥748 nmol/L) | 1,493 | 83.7 (81.5, 86.0) | 786 | 64.2 (61.4, 67.1) | 1,288 | 81.1 (78.8, 83.4) | 582 | 79.0 (75.6, 82.5) | <0.0001 |
| Missing | 11 | — | 9 | — | 9 | — | 2 | — | |
Note: Boldface indicates statistical significance (p<0.05).
p-values calculated using design-based Wald adjusted chi-square test for association.
Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity, and RBC folate concentrations <748 nmol/L.
Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, and obesity.
Category counting toward total number of risk factors for individuals.
Analysis conducted on the pseudo-person level utilizing 2-day dietary data (each participant generated 100 pseudo-persons with 1/100 the weight of the participant).
BMI categories were defined as underweight (BMI<18.5), healthy weight (18.5≤BMI<25), overweight (25≤BMI<30), and obesity (BMI≥30).
Diabetes diagnosis is defined as yes (diagnosed) by self-identification on a questionnaire and yes (undiagnosed) if not indicated on questionnaire and having HbA1C ≥6.5% or fasting blood glucose ≥126 mg/dL, prediabetes is defined as having either HbA1C=5.7%–6.5% or fasting blood glucose=100–125 mg/dL, and no is defined as having HbA1C <5.7% and fasting blood glucose <100 mg/dL.
Cell has <8 degrees of freedom.
Cell has <8 degrees of freedom and a sample size <30.
Does not meet the criteria for prevalence estimate reliability.
CMF, corn masa flour; ECGP, enriched cereal grain product; NHANES, National Health and Nutrition Survey Examination; RBC, red blood cell; RTE, ready-to-eat cereal; SUPP, folic acid containing supplement.
The prevalence of very low food security was statistically different by race and ethnic group (p=0.004) (Table 4): 5.4% (95% CI=4.3, 6.5) among NHW WRA, 10.0% (95% CI=7.2, 12.7) among NHB WRA, 8.6% (95% CI=6.6, 10.5) among Hispanic WRA, and 5.7% (95% CI=2.9, 8.5) among NHO WRA. In addition, there were differences in taking FA-containing supplements by race and ethnic group: 31.5% (95% CI=29.1, 33.9) of NHW WRA, 21.6% (95% CI=18.6, 24.7) of NHB WRA, 22.0% (95% CI=19.4, 24.5) of Hispanic WRA, and 27.9% (95% CI=23.5, 32.4) of NHO WRA (p<0.0001). Including supplements, the proportion of WRA consuming total FA usual intakes <400 μg/d differed by race and ethnic group ranging from 76.5% (95% CI=74.0, 78.9) among NHW WRA up to 85.8% (95% CI=83.0, 88.7) among NHB WRA (p<0.0001). The proportion of WRA with RBC folate concentrations <748 nmol/L differed significantly by race and ethnic group (NHW: 15.9% [95% CI=13.6, 18.1]; NHB: 35.0% [95% CI=32.1, 38.0]; Hispanic: 18.3% [95% CI=16.1, 20.5]; NHO: 20.8% [95% CI=17.4, 24.3]; p<0.0001).
There were significant differences in the prevalence of obesity by race and ethnic group: 30.3% (95% CI=27.7, 32.8) (Table 4) among NHW WRA, 47.4% (95% CI=44.4, 50.4) among NHB WRA, 38.2% (95% CI=35.7, 40.7) among Hispanic WRA, and 27.0% (95% CI=21.8, among NHO WRA (p<0.0001). A significant difference in the prevalence of diabetes by race and ethnic group was also found (NHW: 3.4% [95% CI=2.4, 4.3]; NHB: 6.7% [95% CI=5.2, 8.3]; Hispanic: 7.4% [95% CI=5.9, 8.9]; NHO: 5.0 [95% CI=3.0, 7.0]; p<0.0001).
When restricted to NHANES 2011–March 2020, the prevalence of any risk factor among NHA WRA was 57.1% (95% CI=51.7, 62.5) (Appendix Table 1, available online) in the all-risks profile and 44.6% (95% CI=39.8, 49.4) in the nonfolate risk profile. Very low food security was reported among 2.3% (95% CI=0.8%, 3.8%) of NHA. Approximately 27.5% (95% CI=23.0, 32.1) of NHA WRA consumed FA-containing supplements; including supplements, 83.3% (95% CI=79.5, 87.1) of NHA WRA had usual intakes <400 mcg/d. RBC folate concentrations were <748 nmol/L among 22.8% (95% CI=18.2, 27.4) of NHA WRA. The prevalence of obesity among NHA WRA was 20.1% (95% CI=15.8, 24.4), and the prevalence of diabetes was 4.3% (95% CI=2.4, 6.2). Serum cotinine was elevated among 6.1% (95% CI=3.7, 8.6) of NHA WRA. Chi-square tests showed significant differences by race and ethnicity when restricted to NHANES 2011–March 2020 among NHW, NHB, Hispanic, and NHA WRA.
For the all-risks profile, the proportion of WRA with at least 1 risk factor decreased from 76.9% (95% CI=74.0, 79.8) (Appendix Table 2, available online) among those with income-to-poverty ratio (IPR) <1.0 to 51.6% (95% CI=47.5, 55.6) among those with IPR ≥4.0 (p<0.0001). Likewise, for the nonfolate risks profile, the proportion of WRA with at least 1 risk factor decreased from 70.7% (95% CI=67.8, 73.6) among those with IPR <1.0 to 44.2% (95% CI=40.3, 48.1) among WRA with IPR ≥4.0 (p<0.0001).
The prevalence of very low household food security among WRA decreased as IPR increased (p<0.0001) (Appendix Table 2, available online). FA supplement use increased as IPR increased from 18.0% (95% CI=15.1, 20.9) among those with IPR <1.0 up to 39.5% (95% CI=35.6, 43.5) among those with IPR ≥4.0 (p<0.0001). The percentage of WRA with total FA usual intake <400 μg/day decreased from 87.1% (95% CI=84.5, 89.7) to 70.3% (95% CI=66.3, 74.3; p<0.0001) as IPR increased. Increasing IPR was also associated with a decrease in the prevalence of RBC folate concentrations <748 nmol/L (IPR <1.0: 23.4% [95% CI=19.9, 27.0]; IPR ≥4.0: 15.4% [95% CI=12.5, 18.6]; p=0.003).
With increasing IPR, there were decreases in the prevalence of obesity (IPR <1.0: 38.9% [95% CI=36.1, 41.7]; Appendix Table 2 [available online]; IPR ≥4.0: 21.9% [95% CI=18.5, 25.3]; p<0.0001), diabetes (IPR <1.0: 6.6% [95% CI=5.2, 7.9]; IPR ≥4.0: 2.9% [95% CI=1.6, 4.1]; p=0.0005), and elevated cotinine (IPR <1.0: 29.1% [95% CI=25.5, 32.8]; IPR ≥4.0: 9.5% [95% CI=7.2, 11.7]; p<0.0001).
Serum vitamin B12 has been associated with NTDs independent of folate status.22–24 Data for serum vitamin B12 were available among 2,634 WRA in NHANES 2011–2014. Overall, approximately 2.1% (95% CI=1.4, 2.9) (Appendix Table 3, available online) WRA had serum vitamin B12 deficiency (<148 pmol/L), 10.8% (95% CI=9.5, 12.2) had serum vitamin B12 insufficiency (148–221 pmol/L), and 87.0% (95% CI=85.4, 88.7) had serum vitamin B12 sufficiency (>221 pmol/L). There were no trends by age of deficiency (p=0.57), insufficiency (p=0.60), or sufficiency (p=0.83). Differences were found by race and ethnic group (deficiency: p=0.008; insufficiency: p=0.010; sufficiency: p=0.001). No trends were found with IPR.
DISCUSSION
Prevalence of selected modifiable risk factors for birth defects was assessed among nonpregnant, nonlactating WRA in the U.S. from NHANES 2007–March 2020 using 2 different risk factor profiles: nearly 2 of 3 WRA had at least 1 known risk factor when examining the all-risks profile, and nearly 3 of 5 WRA had at least 1 known risk factor when examining nonfolate risks. These 2 profiles indicate that although improvements can be made in reducing risk through FA tailored education and interventions strategies, there are other modifiable risk factors to consider.
RBC folate status is a reliable biomarker for NTD risk; an optimal RBC folate concentration threshold of 906 nmol/L was established by the WHO for the prevention of NTDs, equivalent to 748 nmol/L using Centers for Disease Control and Prevention microbiologic assay.5,25–27 One in 5 WRA had RBC folate concentrations <748 nmol/L. Low folate status was highest among younger WRA and lower-IPR groups. Within the study timeframe, the prevalence of RBC folate concentrations <748 nmol/L significantly decreased.
Since 1992, the U.S. Public Health Service has recommended the consumption of 400 μg/day of FA for the prevention of NTDs.28 In 1996, the Food and Drug Administration authorized the mandatory fortification of grain products labeled as enriched with 140 μg FA per 100 g of product, and in 2016, the Food and Drug Administration authorized voluntary FA fortification of corn masa products.29,30 Roughly 4 of 5 WRA consumed less than the recommended 400 μg/day FA for NTD prevention. FA consumption was closely tied to age and IPR. Although estimates of the proportion of WRA with low consumption of FA were higher than previously reported numbers, differences were similar to differences reported in the general population in previous studies.31,32 Importantly, FA supplementation is crucial for WRA to achieve the recommended 400 μg/day of FA. Among women who did not take supplements, only 1.3% had intakes at or above the recommended 400 μg/day of FA.
Approximately 72% of WRA did not report consuming supplements containing FA, higher than previously reported.33 Given the decrease in WRA with RBC folate concentrations <748 nmol/L, WRA in the U.S. may have a greater reliance on achieving optimal folate status through FA fortification than through supplementation to achieve NTD prevention. Supplement use trended with age and IPR, with increasing supplement use associating with increasing age and IPR. Although previous studies reported a decline of multivitamin consumption among WRA in the U.S. in the last decade,34 the current analysis did not find a significant trend downward in overall consumption of FA-containing supplements across survey years. However, there was a downward trend in the use of FA supplements containing the recommended ≥400 μg/day.
Analysis of RBC folate concentrations, total FA usual intake, and FA supplement use among WRA in the U.S. suggests improvements in folate status that may be driven through food fortification programs, presenting an opportunity to promote supplementation to decrease reliance on fortified foods. FA supplement use is relatively low, and there are noticeable trends by age and IPR and a downward trend in recent years with taking supplements with the recommended 400 μg/day. These highlight that WRA may benefit from guidance to achieve recommended daily FA intakes for the prevention of NTD-affected pregnancies.
Pregestational diabetes and poor glycemic control are associated with several pregnancy complications, including pre-eclampsia, stillbirth, premature birth, and birth defects, including CHDs and NTDs. It is critical to have good glycemic control prior to pregnancy to mitigate these risks.35 Approximately 4.8% of WRA in the U.S. had diabetes, with 3.5% of WRA having uncontrolled or undiagnosed diabetes and were likely to have poor glycemic control. The prevalence of diabetes increased with increasing age and decreasing IPR. These findings are consistent with a previous report of NHANES data from 2011 to 2016.36 The prevalence of diabetes nearly doubled from 3.2% in 2007–2010 to 6% in 2015–March 2020, with increases in both diagnosed and undiagnosed diabetes.
Prepregnancy obesity is associated with NTDs, CHDs, and other birth defects independent of diabetes status and other risk factors.37–39 Nearly 1 in 3 WRA have obesity in the U.S., similar to previously reported estimates.40 Prevalence of obesity increased with increasing age and decreasing IPR. Although adjustments were made to BMI cut points to more accurately estimate adiposity among NHA WRA, BMI overestimates adiposity for NHB, and guidelines have not been established, limiting interpretations of differences by race and ethnic groups.41 The prevalence of obesity significantly increased over time.
Active tobacco exposure through smoking, vaping, or passive exposure is an established risk factor for NTDs, CHDs, and limb deficiencies.42–46 Although there is no established serum cotinine concentration specifically associated with birth defects, nearly 1 in 5 WRA had serum cotinine concentrations indicative of active tobacco exposure from any source (i.e., smoking, vaping). The prevalence of smoking exposure was lowest among younger WRA, and exposure decreased over time, matching previous reports.47 Smoking exposure was more common among lower IPR categories. Overall, the prevalence of smoking exposure has decreased with time.
Food insecurity is the lack of availability or access to healthy foods and is associated with poorer nutrient intakes, lower dietary supplement use, and higher prevalence of obesity.48,49 Maternal food insecurity has been associated with increased risk of certain birth defects, even after controlling for proxy associations (i.e., FA supplementation, nutrition, BMI, stress).50 Overall, findings in prevalence match previous reports in the U.S.49 About 7.3% of WRA reported very low household food security, with decreasing prevalence as household IPR increased. Reports of very low household food security also increased over time. Although the present analysis did not include data after the coronavirus disease 2019 (COVID-19) pandemic, recent data suggest that COVID-19 initially exacerbated vulnerabilities in food supply and security among adults of reproductive age, although food insecurity stabilized in the years after.51,52
Limitations
NHANES provides a nationally representative sample over several years and benefits from the collection of biomarkers over self-report data. Recent oversampling of minority populations (i.e., Hispanic and NHA) allows for more representative analyses within those populations. However, some strata had limited sample size, and estimates may be unstable, as noted in multiple tables. Serum vitamin B12 concentrations were limited to NHANES 2011–2014, limiting the interpretability of the findings and the reliability of estimates. Some questions such as supplement use may not necessarily reflect the typical consumption patterns over a longer period, and participation rate has decreased over time. Some data may not accurately reflect clinical definitions, for example, clinical diagnosis of diabetes and prediabetes requires abnormal HbA1c or fasting plasma glucose at 2 separate time points, whereas NHANES only collects data from 1 time point, limiting definitions.
Furthermore, this analysis did not account for all possible risk factors. This analysis limited its scope to reported risk factors for selected birth defects that can be improved through public health interventions and impact. Medications and episodic risk factors were not included in this analysis nor were risk factors without established thresholds such as heavy metal exposures. Future research could explore the prevalence of these risk factors.
CONCLUSIONS
The prevalence of known modifiable risk factors associated with selected birth defects are high among U.S. WRA. FA supplement use was low, and the majority of WRA did not consume the recommended 400 μg/day of FA for NTD prevention. The majority of WRA achieved RBC folate >748 nmol/L for the prevention of NTD, suggesting that food fortification programs continue to play an important role in NTD prevention. Within the study period, rates of diabetes among WRA have nearly doubled, highlighting an increased need for diabetes screening among WRA. Excluding folate-specific risk factors still yielded a high proportion of WRA with modifiable risk factors. These data highlight the importance of existing public health programs such as food fortification in NTD prevention. In addition, this study demonstrates an increasing prevalence of diabetes and prediabetes, and these women should see their physician prior to pregnancy to prevent adverse outcomes.
Supplementary Material
Supplemental materials associated with this article can be found in the online version at https://doi.org/10.1016/j.amepre.2025.107947.
Funding:
This research received no external funding beyond staff time and salary.
Disclaimer:
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Footnotes
Data were collected under Human Subject protocols Numbers 2011-17 and 2018-01.
Declaration of interest: None.
CREDIT AUTHOR STATEMENT
Arick Wang: Methodology, Software, Formal analysis, Writing - original draft. Lauren H. Zauche: Software, Writing - original draft, Writing - review & editing, Validation. Krista S. Crider: Supervision, Conceptualization, Writing - review & editing. Cara T. Mai: Writing - review & editing. Yan Ping Qi: Writing - review & editing. Lorraine F. Yeung: Writing - review & editing. Jennifer L. Williams: Writing - review & editing, Supervision.
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