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Abstract：
Orofacial clefts (OFC) have multifactorial aetiology. Established risk factors explain a small proportion of cases.
To evaluate OFC risk by maternal rural residence and race/ethnicity, and test whether these associations changed after US-mandated folic acid fortification.
This population-based case-control study included all non-syndromic OFC cases among Washington State singleton livebirths between 1989-2014 and birth year-matched controls. Data sources included birth certificates and hospital records. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for OFC by maternal rural-urban residence (adjusted for maternal race/ethnicity) and by maternal race/ethnicity. We evaluated additive and multiplicative effect measure modification by time of folic acid fortification (before vs. after). Probabilistic quantitative bias analysis accounted for potential differential case ascertainment for infants born to Black mothers.
The overall non-syndromic OFC birth prevalence was 1.0 per 1000 livebirths (n = 2136 cases). Among controls (n = 25 826), 76% of mothers were urban residents and 72% were of White race/ethnicity. OFC risk was slightly higher for infants born to rural than to urban mothers, adjusting for race/ethnicity (OR 1.12, 95% CI 1.01, 1.25). The association was similar before and after US-mandated folic acid fortification. Compared with infants born to White mothers, OFC risk was higher for American Indian mothers (OR 1.73, 95% CI 1.35, 2.23) and lower for Black (OR 0.62, 95% CI 0.48, 0.81), Hispanic (OR 0.75, 95% CI 0.64, 0.87), and Asian/Pacific Islander (API) mothers (OR 0.87, 95% CI 0.74, 1.02). Bias analysis suggests the observed difference for Black mothers may be explained by selection bias. Post-fortification, the association of OFC with maternal API race/ethnicity decreased and with maternal Black race/ethnicity increased relative to maternal White race/ethnicity.
Infants born to rural mothers and to American Indian mothers in Washington State during 1989-2014 were at higher OFC risk before and after US-mandated folic acid fortification.
To evaluate OFC risk by maternal rural residence and race/ethnicity, and test whether these associations changed after US-mandated folic acid fortification.
This population-based case-control study included all non-syndromic OFC cases among Washington State singleton livebirths between 1989-2014 and birth year-matched controls. Data sources included birth certificates and hospital records. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for OFC by maternal rural-urban residence (adjusted for maternal race/ethnicity) and by maternal race/ethnicity. We evaluated additive and multiplicative effect measure modification by time of folic acid fortification (before vs. after). Probabilistic quantitative bias analysis accounted for potential differential case ascertainment for infants born to Black mothers.
The overall non-syndromic OFC birth prevalence was 1.0 per 1000 livebirths (n = 2136 cases). Among controls (n = 25 826), 76% of mothers were urban residents and 72% were of White race/ethnicity. OFC risk was slightly higher for infants born to rural than to urban mothers, adjusting for race/ethnicity (OR 1.12, 95% CI 1.01, 1.25). The association was similar before and after US-mandated folic acid fortification. Compared with infants born to White mothers, OFC risk was higher for American Indian mothers (OR 1.73, 95% CI 1.35, 2.23) and lower for Black (OR 0.62, 95% CI 0.48, 0.81), Hispanic (OR 0.75, 95% CI 0.64, 0.87), and Asian/Pacific Islander (API) mothers (OR 0.87, 95% CI 0.74, 1.02). Bias analysis suggests the observed difference for Black mothers may be explained by selection bias. Post-fortification, the association of OFC with maternal API race/ethnicity decreased and with maternal Black race/ethnicity increased relative to maternal White race/ethnicity.
Infants born to rural mothers and to American Indian mothers in Washington State during 1989-2014 were at higher OFC risk before and after US-mandated folic acid fortification.
摘要：
面部裂痕（OFC）具有多因素病因。既定的风险因素解释了一小部分病例。
为了评估母亲农村居住地和种族/民族的OFC风险，并测试这些关联在美国强制叶酸强化后是否发生变化。
这项以人群为基础的病例对照研究包括华盛顿州1989-2014年单胎活产和出生年份匹配对照的所有非综合征性OFC病例。数据来源包括出生证明和医院记录。按产妇城乡居住地（针对产妇种族/种族进行调整）和按产妇种族/种族进行的OFC的Logistic回归估计比值比（OR）和95％置信区间（CI）。我们通过叶酸强化时间评估了加性和乘法效应测量值的修改（之前与后)。概率定量偏倚分析解释了黑人母亲出生的婴儿的潜在差异病例确定。
总体非综合征性OFC出生患病率为每1000例活产1.0例(n=2136例)。在对照组中（n=25.826），76％的母亲是城市居民，72％的母亲是白人/种族。农村出生的婴儿的OFC风险略高于城市母亲，调整种族/民族（OR1.12，95%CI1.01，1.25）。美国强制叶酸强化前后的关联相似。与白人母亲所生的婴儿相比，美洲印第安人母亲的OFC风险较高（OR1.73，95％CI1.35，2.23），而Black的OFC风险较低（OR0.62，95％CI0.48，0.81），西班牙裔（OR0.75，95%CI0.64，0.87），和亚洲/太平洋岛民（API）母亲（OR0.87，95%CI0.74，1.02）。偏见分析表明，黑人母亲观察到的差异可以通过选择偏见来解释。设防后，OFC与母体API种族/民族的关联降低,与母体黑人种族/民族的关联增加。
1989-2014年间华盛顿州农村母亲和美洲印第安人母亲所生的婴儿在美国强制叶酸强化之前和之后的OFC风险较高。
为了评估母亲农村居住地和种族/民族的OFC风险，并测试这些关联在美国强制叶酸强化后是否发生变化。
这项以人群为基础的病例对照研究包括华盛顿州1989-2014年单胎活产和出生年份匹配对照的所有非综合征性OFC病例。数据来源包括出生证明和医院记录。按产妇城乡居住地（针对产妇种族/种族进行调整）和按产妇种族/种族进行的OFC的Logistic回归估计比值比（OR）和95％置信区间（CI）。我们通过叶酸强化时间评估了加性和乘法效应测量值的修改（之前与后)。概率定量偏倚分析解释了黑人母亲出生的婴儿的潜在差异病例确定。
总体非综合征性OFC出生患病率为每1000例活产1.0例(n=2136例)。在对照组中（n=25.826），76％的母亲是城市居民，72％的母亲是白人/种族。农村出生的婴儿的OFC风险略高于城市母亲，调整种族/民族（OR1.12，95%CI1.01，1.25）。美国强制叶酸强化前后的关联相似。与白人母亲所生的婴儿相比，美洲印第安人母亲的OFC风险较高（OR1.73，95％CI1.35，2.23），而Black的OFC风险较低（OR0.62，95％CI0.48，0.81），西班牙裔（OR0.75，95%CI0.64，0.87），和亚洲/太平洋岛民（API）母亲（OR0.87，95%CI0.74，1.02）。偏见分析表明，黑人母亲观察到的差异可以通过选择偏见来解释。设防后，OFC与母体API种族/民族的关联降低,与母体黑人种族/民族的关联增加。
1989-2014年间华盛顿州农村母亲和美洲印第安人母亲所生的婴儿在美国强制叶酸强化之前和之后的OFC风险较高。
