Skip to main content
HHS Author Manuscripts logoLink to HHS Author Manuscripts
. Author manuscript; available in PMC: 2026 Mar 31.
Published in final edited form as: Am J Prev Med. 2025 Aug 26;69(6):107947. doi: 10.1016/j.amepre.2025.107947

Trends and Prevalence of Modifiable Risk Factors for Birth Defects Among U.S. Women of Reproductive Age: National Health and Nutrition Examination Survey 2007 to March 2020

Arick Wang 1, Lauren H Zauche 2, Krista S Crider 1, Cara T Mai 1, Yan Ping Qi 1, Lorraine F Yeung 1, Jennifer L Williams 1
PMCID: PMC13034080  NIHMSID: NIHMS2150607  PMID: 40856664

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.24 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.57 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 outcomes810.

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.1621 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
a

Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity, and RBC folate concentrations <748 nmol/L.

b

Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity.

c

Marital status only asked to those aged >20 years; WRA aged ≤20 were categorized as refused/not reported.

d

Category counting toward total number of risk factors for individuals.

e

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).

f

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).

g

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.

h

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).

a

p-values calculated using a trend test.

b

Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity, and RBC folate concentrations <748 nmol/L.

c

Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, and obesity.

d

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).

e

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).

f

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.

g

Category counting toward total number of risk factors for individuals.

h

Cell has <8 degrees of freedom and a sample size <30.

i

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).

a

p-values calculated using trend analysis.

b

Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity, and RBC folate concentrations <748 nmol/L.

c

Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, and obesity.

d

Category counting toward total number of risk factors for individuals.

e

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).

f

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).

g

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.

h

Cell has <8 degrees of freedom and a sample size <30.

i

Cell has <8 degrees of freedom.

j

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).

a

p-values calculated using design-based Wald adjusted chi-square test for association.

b

Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, obesity, and RBC folate concentrations <748 nmol/L.

c

Risk factors include very low food security, smoking exposure (cotinine ≥10 ng/mL), diabetes, prediabetes, and obesity.

d

Category counting toward total number of risk factors for individuals.

e

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).

f

BMI categories were defined as underweight (BMI<18.5), healthy weight (18.5≤BMI<25), overweight (25≤BMI<30), and obesity (BMI≥30).

g

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.

h

Cell has <8 degrees of freedom.

i

Cell has <8 degrees of freedom and a sample size <30.

j

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.2224 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.5,2527 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.3739 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.4246 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

SUP - Wang - Trends and Prevalence of Modifiable Risk Factors for

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.

REFERENCES

  • 1.Centers for Disease Control and Prevention (CDC), Update on overall prevalence of major birth defects-Atlanta, Georgia, 1978–2005, MMWR Morb Mortal Wkly Rep, 57 (1), 2008, 1–5. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5701a2.htm. Accessed Nov 2024. [PubMed] [Google Scholar]
  • 2.Mai CT, Isenburg JL, Canfield MA, et al. National population-based estimates for major birth defects, 2010–2014. Birth Defects Res. 2019;111(18):1420–1435. 10.1002/bdr2.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Hoffman JIE, Kaplan S, Liberthson RR. Prevalence of congenital heart disease. Am Heart J. 2004;147(3):425–439. 10.1016/j.ahj.2003.05.003. [DOI] [PubMed] [Google Scholar]
  • 4.Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998–2005. J Pediatr. 2008;153(6):807–813. 10.1016/j.jpeds.2008.05.059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Crider KS, Qi YP, Yeung LF, et al. Folic acid and the prevention of birth defects: 30 years of opportunity and controversies. Annu Rev Nutr. 2022;42:423–452. 10.1146/annurev-nutr-043020-091647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Honein MA, Devine O, Grosse SD, Reefhuis J. Prevention of orofacial clefts caused by smoking: implications of the Surgeon General’s report. Birth Defects Res A Clin Mol Teratol. 2014;100(11):822–825. 10.1002/bdra.23274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Jenkins KJ, Correa A, Feinstein JA, et al. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007;115(23):2995–3014. 10.1161/CIRCULATIONAHA.106.183216. [DOI] [PubMed] [Google Scholar]
  • 8.American Diabetes Association. 14. Management of diabetes in pregnancy: standards of medical care in Diabetes-2021. Diabetes Care. 2021;44(suppl 1):S200–S210. 10.2337/dc21-S014. [DOI] [PubMed] [Google Scholar]
  • 9.Blankstein AR, Sigurdson SM, Frehlich L, et al. Pre-existing diabetes and stillbirth or perinatal mortality: a systematic review and meta-analysis. Obstet Gynecol. 2024;144(5):608–619. 10.1097/AOG.0000000000005682. [DOI] [PubMed] [Google Scholar]
  • 10.Correa A, Gilboa SM, Botto LD, et al. Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects. Am J Obstet Gynecol. 2012;206(3):218.e1–218.e13. 10.1016/j.ajog.2011.12.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Parker SE, Yazdy MM, Tinker SC, Mitchell AA, Werler MM. The impact of folic acid intake on the association among diabetes mellitus, obesity, and spina bifida. Am J Obstet Gynecol. 2013;209(3):239.e1–239.e8. 10.1016/j.ajog.2013.05.047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Millacura N, Pardo R, Cifuentes L, Suazo J. Effects of folic acid fortification on orofacial clefts prevalence: a meta-analysis. Public Health Nutr. 2017;20(12):2260–2268. 10.1017/S1368980017000878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Liu S, Joseph KS, Luo W, et al. Effect of folic acid food fortification in Canada on congenital heart disease subtypes. Circulation. 2016;134(9):647–655. 10.1161/CIRCULATIONAHA.116.022126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.National health and nutrition examination survey, Centers for Disease Control and Prevention, National Center for Health Statistics, Updated https://www.cdc.gov/nchs/nhanes/index.htm. Accessed 30 July 2025.
  • 15.Dietary Assessment Primer. National Cancer Institute. https://dietassessmentprimer.cancer.gov/. Updated 10 August 2025. Accessed 30 July 2025.
  • 16.National Health and Nutrition Examination Survey (NHANES) 2011–2012. Centers for Disease Control and Prevention, National Center for Health Statistics. https://wwwn.cdc.gov/nchs/nhanes/ContinuousNhanes/Default.aspx?BeginYear=2011. Updated 10 August 2025. Accessed Nov 2024.
  • 17.National Center for Health Statistics National Health and Nutrition Examination Survey (NHANES) 2013–2014. Centers for Disease Control and Prevention, National Center for Health Statistics. https://wwwn.cdc.gov/nchs/nhanes/ContinuousNhanes/Default.aspx?Begin-Year=2013. Updated 10 August 2025. Accessed Nov 2024.
  • 18.National Health and Nutrition Examination Survey (NHANES) 2015–2016. Centers for Disease Control and Prevention, National Center for Health Statistics. https://wwwn.cdc.gov/nchs/nhanes/ContinuousNhanes/Default.aspx?BeginYear=2015. Updated 10 August 2025. Accessed Nov 2024.
  • 19.National Health and Nutrition Examination Survey (NHANES) 2017–2018. Centers for Disease Control and Prevention, National Center for Health Statistics. https://wwwn.cdc.gov/nchs/nhanes/ContinuousNhanes/Default.aspx?BeginYear=2017. Updated 10 August 2025. Accessed Nov 2024.
  • 20.National Health and Nutrition Examination Survey (NHANES) 2007–2008. Centers for Disease Control and Prevention, National Center for Health Statistics. https://wwwn.cdc.gov/nchs/nhanes/ContinuousNhanes/Default.aspx?BeginYear=2007. Updated 10 August 2025. Accessed Nov 2024.
  • 21.National Health and Nutrition Examination Survey (NHANES) 2009–2010. Centers for Disease Control and Prevention, National Center for Health Statistics. https://wwwn.cdc.gov/nchs/nhanes/ContinuousNhanes/Default.aspx?BeginYear=2009. Updated 10 August 2025. Accessed Nov 2024.
  • 22.Molloy AM. Should vitamin B12 status be considered in assessing risk of neural tube defects? Ann N Y Acad Sci. 2018;1414(1):109–125. 10.1111/nyas.13574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Kirke PN, Molloy AM, Daly LE, Burke H, Weir DG, Scott JM. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med. 1993;86(11):703–708. [PubMed] [Google Scholar]
  • 24.Molloy AM, Kirke P, Hillary I, Weir DG, Scott JM. Maternal serum folate and vitamin B12 concentrations in pregnancies associated with neural tube defects. Arch Dis Child. 1985;60(7):660–665. 10.1136/adc.60.7.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Cordero AM, Crider KS, Rogers LM, Cannon MJ and Berry RJ, Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines, MMWR Morb Mortal Wkly Rep, 64 (15), 2015, 421–423. https://pmc.ncbi.nlm.nih.gov/articles/PMC5779552. Accessed 30 July 2025. [PMC free article] [PubMed] [Google Scholar]
  • 26.Pfeiffer CM, Sternberg MR, Hamner HC, et al. Applying inappropriate cutoffs leads to misinterpretation of folate status in the U.S. population. Am J Clin Nutr. 2016;104(6):1607–1615. 10.3945/ajcn.116.138529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Crider KS, Devine O, Hao L, et al. Population red blood cell folate concentrations for prevention of neural tube defects: bayesian model. BMJ. 2014;349:g4554. 10.1136/bmj.g4554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects, MMWR Recomm Rep, 41 (RR-14), 1992, 1–7 https://www.cdc.gov/mmwr/preview/mmwrhtml/00019479.htm. Accessed 30 July 2025 [PubMed] [Google Scholar]
  • 29.Food and Drug Administration, Food additives permitted for direct addition to food for human consumption; folic acid (folacin), final rule, Fed Regist, 64, 1996, 8797–8807. https://www.govinfo.gov/content/pkg/FR-1996-03-05/pdf/96-5012.pdf. Accessed 30 July 2025. [PubMed] [Google Scholar]
  • 30.Flores AL, Cordero AM, Dunn M, et al. Adding folic acid to corn Masa flour: partnering to improve pregnancy outcomes and reduce health disparities. Prev Med. 2018;106:26–30. 10.1016/j.ypmed.2017.11.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Bailey RL, Dodd KW, Gahche JJ, et al. Total folate and folic acid intake from foods and dietary supplements in the United States: 2003–2006. Am J Clin Nutr. 2010;91(1):231–237. 10.3945/ajcn.2009.28427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.USDA ARS, Usual Nutrient Intake From Food and Beverages, by Gender and Age, What We Eat in America, NHANES 2013–2016, 2019. https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/usual/Usual_Intake_gender_WWEIA_2013_2016.pdf. Accessed 30 July 2025.
  • 33.Centers for Disease Control and Prevention (CDC), Use of supplements containing folic acid among women of childbearing age–United States 2007, MMWR. Morbidity and Mortality Weekly Report, 57 (1), 2008, 5–8. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5701a3.htm. Accessed 30 July 2025 [PubMed] [Google Scholar]
  • 34.Wong EC, Rose CE, Flores AL, Yeung LF. Trends in multivitamin use among women of reproductive age: United States, 2006–2016. J Womens Health (Larchmt). 2019;28(1):37–45. 10.1089/jwh.2018.7075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Correa A, Gilboa SM, Besser LM, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol. 2008;199(3):237.e1–237.e9. 10.1016/j.ajog.2008.06.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Azeez O, Kulkarni A, Kuklina EV, Kim SY, Cox S. Hypertension and diabetes in non-pregnant women of reproductive age in the United States. Prev Chronic Dis. 2019;16:E146. 10.5888/pcd16.190105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Anderson JL, Waller DK, Canfield MA, Shaw GM, Watkins ML, Werler MM. Maternal obesity, gestational diabetes, and central nervous system birth defects. Epidemiology. 2005;16(1):87–92. 10.1097/01.ede.0000147122.97061.bb. [DOI] [PubMed] [Google Scholar]
  • 38.Stothard KJ, Tennant PWG, Bell R, Rankin J. Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis. JAMA. 2009;301(6):636–650. 10.1001/jama.2009.113. [DOI] [PubMed] [Google Scholar]
  • 39.Tinker SC, Gilboa SM, Moore CA, et al. Modification of the association between diabetes and birth defects by obesity, National Birth Defects Prevention Study, 1997–2011. Birth Defects Res. 2021;113(14):1084–1097. 10.1002/bdr2.1900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Hales CM, Carroll MD, Fryar CD and Ogden CL, Prevalence of obesity and severe obesity among adults: United States, 2017–2018, NCHS Data Brief, (360), 2020, 1–8. https://www.cdc.gov/nchs/products/databriefs/db360.htm. Accessed 30 July 2025 [PubMed] [Google Scholar]
  • 41.Flegal KM, Ogden CL, Yanovski JA, et al. High adiposity and high body mass index-for-age in U.S. children and adolescents overall and by race-ethnic group. Am J Clin Nutr. 2010;91(4):1020–1026. 10.3945/ajcn.2009.28589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Caspers KM, Romitti PA, Lin S, et al. Maternal periconceptional exposure to cigarette smoking and congenital limb deficiencies. Paediatr Perinat Epidemiol. 2013;27(6):509–520. 10.1111/ppe.12075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Hoyt AT, Canfield MA, Romitti PA, et al. Associations between maternal periconceptional exposure to secondhand tobacco smoke and major birth defects. Am J Obstet Gynecol. 2016;215(5):613.e1–613.e11. 10.1016/j.ajog.2016.07.022. [DOI] [PubMed] [Google Scholar]
  • 44.Lee LJ, Lupo PJ. Maternal smoking during pregnancy and the risk of congenital heart defects in offspring: a systematic review and meta-analysis. Pediatr Cardiol. 2013;34(2):398–407. 10.1007/s00246-012-0470-x. [DOI] [PubMed] [Google Scholar]
  • 45.Yin Z, Xu W, Xu C, et al. A population-based case-control study of risk factors for neural tube defects in Shenyang, China. Childs Nerv Syst. 2011;27(1):149–154. 10.1007/s00381-010-1198-7. [DOI] [PubMed] [Google Scholar]
  • 46.Zhao L, Chen L, Yang T, et al. Parental smoking and the risk of congenital heart defects in offspring: an updated meta-analysis of observational studies. Eur J Prev Cardiol. 2020;27(12):1284–1293. 10.1177/2047487319831367. [DOI] [PubMed] [Google Scholar]
  • 47.Cornelius M, Wang T, Jamal A, Loretan C, Neff L. Tobacco product use among adults–United States. 2019. 2020;69(46):1736–1742. 10.15585/mmwr.mm6946a4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Coleman-Jensen A, Gregory C, Singh A. Household food security in the United States in 2013 USDA-ERS economic research report SSRN J. 2015. Preprint. Online October 26. 10.2139/ssrn.2504067. [DOI] [Google Scholar]
  • 49.Hernandez DC, Reesor LM, Murillo R. Food insecurity and adult overweight/obesity: gender and race/ethnic disparities. Appetite. 2017;117:373–378. 10.1016/j.appet.2017.07.010. [DOI] [PubMed] [Google Scholar]
  • 50.Carmichael SL, Yang W, Herring A, Abrams B, Shaw GM. Maternal food insecurity is associated with increased risk of certain birth defects. J Nutr. 2007;137(9):2087–2092. 10.1093/jn/137.9.2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Wolfson JA, Leung CW. Food insecurity during COVID-19: an acute crisis with long-term health implications. Am J Public Health. 2020;110(12):1763–1765. 10.2105/AJPH.2020.305953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Fan Z, Yang AM, Lehr M, et al. Food insecurity across age groups in the United States during the COVID-19 pandemic. Int J Environ Res Public Health. 2024;21(8):1078. 10.3390/ijerph21081078. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

SUP - Wang - Trends and Prevalence of Modifiable Risk Factors for

RESOURCES