Teratology Society 2014

BELLEVUE, WASH. – Registries that collect data on pregnant women’s exposures to medical products and outcomes are contributing to product safety in this population, as intended, suggests an exploratory review conducted by the Food and Drug Administration.

But they do have some shortcomings.

"Currently, pregnancy registries are the most common type of postapproval study in pregnant women that are either required or requested by FDA from pharmaceutical companies," first author Dr. Leyla Sahin, an FDA medical officer on the Pediatric and Maternal Health Staff of the Maternal Health Team, in Harvard, Mass., explained at the annual meeting of the Teratology Society.

"However, recently, the Agency has had a concern that pregnancy registries often fail to provide useful information, and usually this is due to low enrollment. ... Companies will come back to the agency a few years later and say, ‘We have been unable to recruit enough patients into our study, so please release us from our postmarketing requirement,’" she added. So, FDA sought to discover "what characteristics determine a successful registry so that we could then provide guidance to industry."

Dr. Sahin and her colleagues studied 38 pregnancy registries listed on the FDA’s Pregnancy Registry website that tracked 59 medical products–drugs, biologics, or vaccines.

Findings showed that for 12% of the products, registry results led to changes in the labeling for that product, as in the cases of the Bupropion Pregnancy Registry and the Pregnancy Registry for Varicella Zoster Virus–Containing Vaccines.

Similarly, for 12% of products, registry results had informed practice guidelines, as in the cases of the Pregnancy Registry for Gardasil and the Antiretroviral Pregnancy Registry.

Of the seven products that had registry data added to their approved labeling, 86% also had their results published in a peer-reviewed journal. Of the 59 products overall, 37% had interim or final registry results published in a peer-reviewed journal.

But the registries did struggle with enrollment. Overall, 17% had been closed for feasibility reasons, meaning they had not been able to enroll sufficient patients. And of the 22 products that had a target enrollment stated in the pregnancy registry protocol, just 14% had achieved that enrollment.

Additionally, for the 21 products having registries that provided information about loss to follow-up and that had at least moderate enrollment, the median rate of loss to follow-up of enrolled women was 23.4%.

"What we took away from this review is that basically, pregnancy registries have contributed safety data to labeling and to clinical guidelines, and have been published in the medical literature. However, there is room for improvement in terms of doing a better job with recruitment and enrollment into these studies," commented Dr. Sahin.

"Unfortunately, we are not able to draw conclusions from this review on the characteristics that result in a successful registry because of limitations" such as the lack of inclusion of disease-based registries, the review’s exploratory nature (as opposed to a comprehensive one), and no assessment of factors such as registries’ data quality, resources used, and expertise.

"Pregnancy registries by themselves may not be sufficient to collect data that inform product labeling, so we need to explore complementary study methods to do this," Dr. Sahin maintained. To address that and related issues, the agency held a public meeting in May.

"The key messages that we obtained from experts and stakeholders at the meeting are that pregnancy registries continue to have an important role in data collection, but that improvements are needed in the methodology and conduct," she reported. Participants suggested, for example, using a combination of approaches that include complementary study designs to overcome the limitations of individual study designs; developing personal connections with both patients and health care providers, using "champions" enthusiastic about registries to boost recruitment and enrollment; and harnessing electronic medical records to improve data collection.

"The next steps now for the agency are to review the transcripts from the public meeting, and then to develop future policies in terms of what to request as postmarketing requirements from companies. And then developing policy, and integrating what we got from the public meeting into revising the pregnancy registry guidance for industry," Dr. Sahin said. Plans additionally include "working on developing further communication and outreach, looking at the FDA Pregnancy Registry web page, and how that can be specifically designed to meet the needs of all stakeholders, and then also continuing to explore opportunities for collaboration through public-private partnership."

In an interview, session cochair Marlissa Campbell, Ph.D., said, "In general, I think FDA’s purpose in reviewing the registries in order to help manufacturers improve the process to obtain useful data is good, and potentially very important. I had not known that attaining enrollment goals for these registries was proving to be so difficult."

The feedback from the public meeting may go a long way toward improving data collection in these registries, she agreed. "Getting input from clinicians, as well as manufacturers and other registry programs should help the agency formulate next steps." Dr. Campbell is staff toxicologist with the Office of Environmental Health Hazard Assessment (OEHHA), California Environmental Protection Agency, Sacramento.

Dr. Sahin disclosed no relevant conflicts of interest.

Do you tell your pregnant patients about pregnancy exposure registries and suggest that they sign up? Take our Quick Poll on the ObGyn News homepage.

BELLEVUE, WASH. – Registries that collect data on pregnant women’s exposures to medical products and outcomes are contributing to product safety in this population, as intended, suggests an exploratory review conducted by the Food and Drug Administration.

But they do have some shortcomings.

"Currently, pregnancy registries are the most common type of postapproval study in pregnant women that are either required or requested by FDA from pharmaceutical companies," first author Dr. Leyla Sahin, an FDA medical officer on the Pediatric and Maternal Health Staff of the Maternal Health Team, in Harvard, Mass., explained at the annual meeting of the Teratology Society.

"However, recently, the Agency has had a concern that pregnancy registries often fail to provide useful information, and usually this is due to low enrollment. ... Companies will come back to the agency a few years later and say, ‘We have been unable to recruit enough patients into our study, so please release us from our postmarketing requirement,’" she added. So, FDA sought to discover "what characteristics determine a successful registry so that we could then provide guidance to industry."

Dr. Sahin and her colleagues studied 38 pregnancy registries listed on the FDA’s Pregnancy Registry website that tracked 59 medical products–drugs, biologics, or vaccines.

Findings showed that for 12% of the products, registry results led to changes in the labeling for that product, as in the cases of the Bupropion Pregnancy Registry and the Pregnancy Registry for Varicella Zoster Virus–Containing Vaccines.

Similarly, for 12% of products, registry results had informed practice guidelines, as in the cases of the Pregnancy Registry for Gardasil and the Antiretroviral Pregnancy Registry.

Of the seven products that had registry data added to their approved labeling, 86% also had their results published in a peer-reviewed journal. Of the 59 products overall, 37% had interim or final registry results published in a peer-reviewed journal.

But the registries did struggle with enrollment. Overall, 17% had been closed for feasibility reasons, meaning they had not been able to enroll sufficient patients. And of the 22 products that had a target enrollment stated in the pregnancy registry protocol, just 14% had achieved that enrollment.

Additionally, for the 21 products having registries that provided information about loss to follow-up and that had at least moderate enrollment, the median rate of loss to follow-up of enrolled women was 23.4%.

"What we took away from this review is that basically, pregnancy registries have contributed safety data to labeling and to clinical guidelines, and have been published in the medical literature. However, there is room for improvement in terms of doing a better job with recruitment and enrollment into these studies," commented Dr. Sahin.

"Unfortunately, we are not able to draw conclusions from this review on the characteristics that result in a successful registry because of limitations" such as the lack of inclusion of disease-based registries, the review’s exploratory nature (as opposed to a comprehensive one), and no assessment of factors such as registries’ data quality, resources used, and expertise.

"Pregnancy registries by themselves may not be sufficient to collect data that inform product labeling, so we need to explore complementary study methods to do this," Dr. Sahin maintained. To address that and related issues, the agency held a public meeting in May.

"The key messages that we obtained from experts and stakeholders at the meeting are that pregnancy registries continue to have an important role in data collection, but that improvements are needed in the methodology and conduct," she reported. Participants suggested, for example, using a combination of approaches that include complementary study designs to overcome the limitations of individual study designs; developing personal connections with both patients and health care providers, using "champions" enthusiastic about registries to boost recruitment and enrollment; and harnessing electronic medical records to improve data collection.

"The next steps now for the agency are to review the transcripts from the public meeting, and then to develop future policies in terms of what to request as postmarketing requirements from companies. And then developing policy, and integrating what we got from the public meeting into revising the pregnancy registry guidance for industry," Dr. Sahin said. Plans additionally include "working on developing further communication and outreach, looking at the FDA Pregnancy Registry web page, and how that can be specifically designed to meet the needs of all stakeholders, and then also continuing to explore opportunities for collaboration through public-private partnership."

In an interview, session cochair Marlissa Campbell, Ph.D., said, "In general, I think FDA’s purpose in reviewing the registries in order to help manufacturers improve the process to obtain useful data is good, and potentially very important. I had not known that attaining enrollment goals for these registries was proving to be so difficult."

The feedback from the public meeting may go a long way toward improving data collection in these registries, she agreed. "Getting input from clinicians, as well as manufacturers and other registry programs should help the agency formulate next steps." Dr. Campbell is staff toxicologist with the Office of Environmental Health Hazard Assessment (OEHHA), California Environmental Protection Agency, Sacramento.

Dr. Sahin disclosed no relevant conflicts of interest.

Do you tell your pregnant patients about pregnancy exposure registries and suggest that they sign up? Take our Quick Poll on the ObGyn News homepage.

BELLEVUE, WASH. – Registries that collect data on pregnant women’s exposures to medical products and outcomes are contributing to product safety in this population, as intended, suggests an exploratory review conducted by the Food and Drug Administration.

But they do have some shortcomings.

"Currently, pregnancy registries are the most common type of postapproval study in pregnant women that are either required or requested by FDA from pharmaceutical companies," first author Dr. Leyla Sahin, an FDA medical officer on the Pediatric and Maternal Health Staff of the Maternal Health Team, in Harvard, Mass., explained at the annual meeting of the Teratology Society.

"However, recently, the Agency has had a concern that pregnancy registries often fail to provide useful information, and usually this is due to low enrollment. ... Companies will come back to the agency a few years later and say, ‘We have been unable to recruit enough patients into our study, so please release us from our postmarketing requirement,’" she added. So, FDA sought to discover "what characteristics determine a successful registry so that we could then provide guidance to industry."

Dr. Sahin and her colleagues studied 38 pregnancy registries listed on the FDA’s Pregnancy Registry website that tracked 59 medical products–drugs, biologics, or vaccines.

Findings showed that for 12% of the products, registry results led to changes in the labeling for that product, as in the cases of the Bupropion Pregnancy Registry and the Pregnancy Registry for Varicella Zoster Virus–Containing Vaccines.

Similarly, for 12% of products, registry results had informed practice guidelines, as in the cases of the Pregnancy Registry for Gardasil and the Antiretroviral Pregnancy Registry.

Of the seven products that had registry data added to their approved labeling, 86% also had their results published in a peer-reviewed journal. Of the 59 products overall, 37% had interim or final registry results published in a peer-reviewed journal.

But the registries did struggle with enrollment. Overall, 17% had been closed for feasibility reasons, meaning they had not been able to enroll sufficient patients. And of the 22 products that had a target enrollment stated in the pregnancy registry protocol, just 14% had achieved that enrollment.

Additionally, for the 21 products having registries that provided information about loss to follow-up and that had at least moderate enrollment, the median rate of loss to follow-up of enrolled women was 23.4%.

"What we took away from this review is that basically, pregnancy registries have contributed safety data to labeling and to clinical guidelines, and have been published in the medical literature. However, there is room for improvement in terms of doing a better job with recruitment and enrollment into these studies," commented Dr. Sahin.

"Unfortunately, we are not able to draw conclusions from this review on the characteristics that result in a successful registry because of limitations" such as the lack of inclusion of disease-based registries, the review’s exploratory nature (as opposed to a comprehensive one), and no assessment of factors such as registries’ data quality, resources used, and expertise.

"Pregnancy registries by themselves may not be sufficient to collect data that inform product labeling, so we need to explore complementary study methods to do this," Dr. Sahin maintained. To address that and related issues, the agency held a public meeting in May.

"The key messages that we obtained from experts and stakeholders at the meeting are that pregnancy registries continue to have an important role in data collection, but that improvements are needed in the methodology and conduct," she reported. Participants suggested, for example, using a combination of approaches that include complementary study designs to overcome the limitations of individual study designs; developing personal connections with both patients and health care providers, using "champions" enthusiastic about registries to boost recruitment and enrollment; and harnessing electronic medical records to improve data collection.

"The next steps now for the agency are to review the transcripts from the public meeting, and then to develop future policies in terms of what to request as postmarketing requirements from companies. And then developing policy, and integrating what we got from the public meeting into revising the pregnancy registry guidance for industry," Dr. Sahin said. Plans additionally include "working on developing further communication and outreach, looking at the FDA Pregnancy Registry web page, and how that can be specifically designed to meet the needs of all stakeholders, and then also continuing to explore opportunities for collaboration through public-private partnership."

In an interview, session cochair Marlissa Campbell, Ph.D., said, "In general, I think FDA’s purpose in reviewing the registries in order to help manufacturers improve the process to obtain useful data is good, and potentially very important. I had not known that attaining enrollment goals for these registries was proving to be so difficult."

The feedback from the public meeting may go a long way toward improving data collection in these registries, she agreed. "Getting input from clinicians, as well as manufacturers and other registry programs should help the agency formulate next steps." Dr. Campbell is staff toxicologist with the Office of Environmental Health Hazard Assessment (OEHHA), California Environmental Protection Agency, Sacramento.

Dr. Sahin disclosed no relevant conflicts of interest.

Do you tell your pregnant patients about pregnancy exposure registries and suggest that they sign up? Take our Quick Poll on the ObGyn News homepage.

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.

BELLEVUE, WASH. – Women with autoimmune diseases who take corticosteroids and disease-modifying antirheumatic drugs later in pregnancy have an increased risk of preterm birth, but this association is largely explained by confounding with sociodemographic and clinical factors and disease severity, a study showed.

Researchers prospectively studied 678 pregnant women from the MotherToBaby database who had rheumatoid arthritis, psoriasis or psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease. They focused on steroid use and disease-modifying antirheumatic drug (DMARD) use in the 16 weeks before delivery.

The results presented at the annual meeting of the Teratology Society showed that the incidence of preterm birth (birth before 37 weeks of gestation) was 19.2% among women using only steroids, 11.9% among those using only DMARDs, and 25.0% among those using both, compared with 11.2% among women who used neither throughout pregnancy.

In unadjusted analyses, women taking both steroids and DMARDs had significantly higher odds of preterm birth relative to peers who took neither (relative risk, 2.23), reported lead author Kristin Palmsten, Sc.D., of the University of California, San Diego.

But this risk was attenuated and no longer significant after adjustment for sociodemographic and clinical factors, such as age, race/ethnicity, parity, prior preterm birth, twin pregnancy, prepregnancy hypertension, depression, and use of nonsteroidal anti-inflammatory drugs.

It was attenuated further still after additional adjustment for the severity of autoimmune disease earlier in pregnancy, as assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI) in analyses that excluded patients with Crohn’s disease (because they were not asked about disease severity).

The use of steroids alone and the use of DMARDs alone were not associated with a significantly elevated risk of preterm birth in either unadjusted or adjusted analyses.

The findings showed that confounders at least partially explain the heightened risk of preterm birth associated with autoimmune therapy, according to Dr. Palmsten.

A major study strength was exposure ascertainment, as the women were directly asked about their medication use several times during pregnancy, she noted. A limitation was the potential lack of generalizability, as the women studied were predominantly white and had higher socioeconomic status and lower disease severity.

In ongoing analyses, the investigators are looking at the proportions of preterm births that were spontaneous and medically indicated, and at the specific gestational age of the preterm births.

"I’d like to confirm the results in a different population; I’d like to look at this association in the Medicaid population, which is a low-income population," Dr. Palmsten added. "And I think preterm birth subtypes should be considered in further investigation. I’d also like to explore the timing of exposure and dose as well."

Session attendee Dr. Jan M. Friedman of the University of British Columbia in Vancouver noted the wide confidence intervals seen in analyses. "Obviously, that’s partially a function of the fact that the groups are fairly small. Is this an ongoing study? Will you have more data, more patients to look at in a year or something?" he asked.

"It is ongoing," Dr. Palmsten replied. "I don’t think that we’ll have 500 women exposed even after a year. But I do hope to address that with the Medicaid data because that would have a very large population."

Dr. Palmsten disclosed no relevant conflicts of interest. The MotherToBaby Pregnancy Study is sponsored by AbbVie, Amgen, Sanofi-Aventis, Apotex, Barr, Par Pharmaceutical, Sandoz, Teva, Bristol-Myers Squibb, Roche/Genentech, UCB Pharma, Pfizer, and Janssen.

BELLEVUE, WASH. – Hispanic women are much more likely than white women to give birth to an infant with small or no ears, an analysis of data from the National Birth Defects Prevention Study found.

In the NBDPS study of more than 8,500 births in the United States, the incidence of congenital isolated anotia or microtia was about three times higher among U.S.-born Hispanic women and five times higher among foreign-born Hispanic women, compared with non-Hispanic white women.

The elevation of risk for Hispanic women was especially pronounced if they had not completed high school, were obese, or smoked around the time of conception, and if they were less acculturated to the U.S. lifestyle.

"Anotia/microtia represents an extreme example of a racial/ethnic disparity in birth defects, especially among Hispanics," commented lead investigator Adrienne T. Hoyt, an epidemiologist with the Texas Department of State Health Services in Austin.

"These differences may be due to a combination of environmental, cultural, and genetic factors, which I think point a way toward future research in this area," she added at the annual meeting of the Teratology Society.

Session attendee Dr. Jan M. Friedman, a medical geneticist at the University of British Columbia in Vancouver, commented, "I’m having a hard time trying to get my head around how these factors are related to microtia/anotia if it isn’t poverty. Do you think they could all be just surrogates for poverty? [Lack of money] obviously has an influence on diet, access to medical care, and many other things."

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University, concurred, saying, "That is a question I was going to ask. ... So I know education was part of the analysis, but what socioeconomic status variables did you adjust for?"

"We did adjust for household income in all of our models. Unfortunately, this is a variable collected by the NBDPS, and it has a high rate of ‘missing,’ mothers who elected not to give household income. I think we had over 10% missing for this particular variable, but we did include that in the models."

The investigators analyzed data for 8,786 births between 1997 and 2007. All analyses excluded women with diabetes as it has been shown to be a strong risk factor for anotia and microtia, noted Ms. Hoyt.

The incidence of birth of an infant with anotia or microtia was 7.2% among U.S.-born Hispanic women and 11.0% among foreign-born Hispanic women, dramatically higher than the 2.3% among non-Hispanic white women, she reported.

In adjusted analyses stratified by sociodemographic factors, the elevated risk of having an infant with anotia/microtia associated with Hispanic versus white ethnicity was especially marked among strata of women having less than 12 years of education (odds ratios, 4.9-8.8), those having a body mass index exceeding 30 kg/m² before conceiving (OR, 3.7-11.9), those who smoked in the periconceptional period (OR, 8.2 for foreign-born women), and those who did not take folic acid supplements periconceptionally (OR, 2.7-5.2).

In further analyses looking at acculturation factors and including infants having both a non-Hispanic white mother and father as the comparator group, the risk was elevated for Hispanic mothers who predominantly spoke English (odds ratio, 2.4), but more so for those who predominantly spoke Spanish (OR, 4.5). Similarly, the risk was elevated for U.S.-born Hispanic women (OR, 2.5), but more so for Mexican-born women who immigrated after age 5 (OR, 4.9).

Ms. Hoyt disclosed no relevant financial conflicts.

BELLEVUE, WASH. – Hispanic women are much more likely than white women to give birth to an infant with small or no ears, an analysis of data from the National Birth Defects Prevention Study found.

In the NBDPS study of more than 8,500 births in the United States, the incidence of congenital isolated anotia or microtia was about three times higher among U.S.-born Hispanic women and five times higher among foreign-born Hispanic women, compared with non-Hispanic white women.

The elevation of risk for Hispanic women was especially pronounced if they had not completed high school, were obese, or smoked around the time of conception, and if they were less acculturated to the U.S. lifestyle.

"Anotia/microtia represents an extreme example of a racial/ethnic disparity in birth defects, especially among Hispanics," commented lead investigator Adrienne T. Hoyt, an epidemiologist with the Texas Department of State Health Services in Austin.

"These differences may be due to a combination of environmental, cultural, and genetic factors, which I think point a way toward future research in this area," she added at the annual meeting of the Teratology Society.

Session attendee Dr. Jan M. Friedman, a medical geneticist at the University of British Columbia in Vancouver, commented, "I’m having a hard time trying to get my head around how these factors are related to microtia/anotia if it isn’t poverty. Do you think they could all be just surrogates for poverty? [Lack of money] obviously has an influence on diet, access to medical care, and many other things."

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University, concurred, saying, "That is a question I was going to ask. ... So I know education was part of the analysis, but what socioeconomic status variables did you adjust for?"

"We did adjust for household income in all of our models. Unfortunately, this is a variable collected by the NBDPS, and it has a high rate of ‘missing,’ mothers who elected not to give household income. I think we had over 10% missing for this particular variable, but we did include that in the models."

The investigators analyzed data for 8,786 births between 1997 and 2007. All analyses excluded women with diabetes as it has been shown to be a strong risk factor for anotia and microtia, noted Ms. Hoyt.

The incidence of birth of an infant with anotia or microtia was 7.2% among U.S.-born Hispanic women and 11.0% among foreign-born Hispanic women, dramatically higher than the 2.3% among non-Hispanic white women, she reported.

In adjusted analyses stratified by sociodemographic factors, the elevated risk of having an infant with anotia/microtia associated with Hispanic versus white ethnicity was especially marked among strata of women having less than 12 years of education (odds ratios, 4.9-8.8), those having a body mass index exceeding 30 kg/m² before conceiving (OR, 3.7-11.9), those who smoked in the periconceptional period (OR, 8.2 for foreign-born women), and those who did not take folic acid supplements periconceptionally (OR, 2.7-5.2).

In further analyses looking at acculturation factors and including infants having both a non-Hispanic white mother and father as the comparator group, the risk was elevated for Hispanic mothers who predominantly spoke English (odds ratio, 2.4), but more so for those who predominantly spoke Spanish (OR, 4.5). Similarly, the risk was elevated for U.S.-born Hispanic women (OR, 2.5), but more so for Mexican-born women who immigrated after age 5 (OR, 4.9).

Ms. Hoyt disclosed no relevant financial conflicts.

BELLEVUE, WASH. – Hispanic women are much more likely than white women to give birth to an infant with small or no ears, an analysis of data from the National Birth Defects Prevention Study found.

In the NBDPS study of more than 8,500 births in the United States, the incidence of congenital isolated anotia or microtia was about three times higher among U.S.-born Hispanic women and five times higher among foreign-born Hispanic women, compared with non-Hispanic white women.

The elevation of risk for Hispanic women was especially pronounced if they had not completed high school, were obese, or smoked around the time of conception, and if they were less acculturated to the U.S. lifestyle.

"Anotia/microtia represents an extreme example of a racial/ethnic disparity in birth defects, especially among Hispanics," commented lead investigator Adrienne T. Hoyt, an epidemiologist with the Texas Department of State Health Services in Austin.

"These differences may be due to a combination of environmental, cultural, and genetic factors, which I think point a way toward future research in this area," she added at the annual meeting of the Teratology Society.

Session attendee Dr. Jan M. Friedman, a medical geneticist at the University of British Columbia in Vancouver, commented, "I’m having a hard time trying to get my head around how these factors are related to microtia/anotia if it isn’t poverty. Do you think they could all be just surrogates for poverty? [Lack of money] obviously has an influence on diet, access to medical care, and many other things."

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University, concurred, saying, "That is a question I was going to ask. ... So I know education was part of the analysis, but what socioeconomic status variables did you adjust for?"

"We did adjust for household income in all of our models. Unfortunately, this is a variable collected by the NBDPS, and it has a high rate of ‘missing,’ mothers who elected not to give household income. I think we had over 10% missing for this particular variable, but we did include that in the models."

The investigators analyzed data for 8,786 births between 1997 and 2007. All analyses excluded women with diabetes as it has been shown to be a strong risk factor for anotia and microtia, noted Ms. Hoyt.

The incidence of birth of an infant with anotia or microtia was 7.2% among U.S.-born Hispanic women and 11.0% among foreign-born Hispanic women, dramatically higher than the 2.3% among non-Hispanic white women, she reported.

In adjusted analyses stratified by sociodemographic factors, the elevated risk of having an infant with anotia/microtia associated with Hispanic versus white ethnicity was especially marked among strata of women having less than 12 years of education (odds ratios, 4.9-8.8), those having a body mass index exceeding 30 kg/m² before conceiving (OR, 3.7-11.9), those who smoked in the periconceptional period (OR, 8.2 for foreign-born women), and those who did not take folic acid supplements periconceptionally (OR, 2.7-5.2).

In further analyses looking at acculturation factors and including infants having both a non-Hispanic white mother and father as the comparator group, the risk was elevated for Hispanic mothers who predominantly spoke English (odds ratio, 2.4), but more so for those who predominantly spoke Spanish (OR, 4.5). Similarly, the risk was elevated for U.S.-born Hispanic women (OR, 2.5), but more so for Mexican-born women who immigrated after age 5 (OR, 4.9).

Ms. Hoyt disclosed no relevant financial conflicts.

BELLEVUE, WASH. – Early gestational exposure to agricultural pesticides is only weakly linked to the risk of gastroschisis in offspring, suggests a case-control study conducted in California’s San Joaquin Valley, an area having among the highest levels of pesticide use nationwide.

Using data from the state and the National Birth Defects Prevention Study for the years 1997-2012, investigators led by Gary M. Shaw, Dr.P.H., assessed maternal exposure during early pregnancy to hundreds of chemicals as ascertained from state pesticide reporting data by geographic area and the women’s address of residence, obtained during interviews.

Analyses were based on 156 live births, fetal deaths, or pregnancy terminations affected by gastroschisis and 785 unaffected matched controls.

"Gastroschisis is a rather unique birth defect. It has a very unique epidemiology," noted Dr. Shaw, who is a professor of clinical research and a doctor of public health in the pediatrics department at Stanford (Calif.) University. "It’s one of a few or perhaps the only one that has been increasing around the world for the last 20-30 years, and it really looks like it’s a disease of young women from what we observe." Teenagers, for example, have a seven to nine times higher risk than do older women.

Overall, 35% of cases and 38% of controls had maternal pesticide exposure in early pregnancy, Dr. Shaw reported at the annual meeting of the Teratology Society. The most common chemical groups to which women had been exposed were poly-alkyl-oxy compounds, glycophosphates, organophosphorus insecticides, alcohols/ethers, and pyrethroids.

However, in adjusted analyses of 52 chemical groups restricted to those for which more than four cases or controls were exposed, only one – the triazine group – was associated with an increased risk of gastroschisis (odds ratio, 1.7), and that association was merely borderline significant, with the confidence interval including unity.

Similarly, in adjusted analyses of 233 individual chemicals restricted to those for which more than four cases or controls were exposed, only two – oxyfluorfen (OR, 1.6) and petroleum distillates (OR, 2.5) – showed an association with this risk; in these cases, the confidence intervals did not include unity.

"We basically got a general lack of association in a discovery, hypothesis-generating study. We have a detailed exposure assessment. ... We conducted many comparisons, and we’ve got modest sample sizes," Dr. Shaw concluded. "And the kicker is that none of the associations we looked at seemed to stand up for young maternal age."

"This is a useful negative study, and it is noteworthy that, even without correcting for multiple comparisons, there were no impressive positive findings," commented session cochair Dr. James Mills, an investigator with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md.

In additional study results, analyses of exposure to those chemicals classified as reproductive toxicants, ones listed in California’s Proposition 65 (which aims to eliminate carcinogenic and teratogenic agents from drinking water and consumer products), and known endocrine disruptors, either alone or in combinations, did not alter the findings, according to Dr. Shaw.

Furthermore, there was no significant association of the combination of pesticide exposure and air pollution exposure (any of either vs. none) and the risk of gastroschisis.

Dr. Shaw had no relevant conflicts of interest.

BELLEVUE, WASH. – Early gestational exposure to agricultural pesticides is only weakly linked to the risk of gastroschisis in offspring, suggests a case-control study conducted in California’s San Joaquin Valley, an area having among the highest levels of pesticide use nationwide.

Using data from the state and the National Birth Defects Prevention Study for the years 1997-2012, investigators led by Gary M. Shaw, Dr.P.H., assessed maternal exposure during early pregnancy to hundreds of chemicals as ascertained from state pesticide reporting data by geographic area and the women’s address of residence, obtained during interviews.

Analyses were based on 156 live births, fetal deaths, or pregnancy terminations affected by gastroschisis and 785 unaffected matched controls.

"Gastroschisis is a rather unique birth defect. It has a very unique epidemiology," noted Dr. Shaw, who is a professor of clinical research and a doctor of public health in the pediatrics department at Stanford (Calif.) University. "It’s one of a few or perhaps the only one that has been increasing around the world for the last 20-30 years, and it really looks like it’s a disease of young women from what we observe." Teenagers, for example, have a seven to nine times higher risk than do older women.

Overall, 35% of cases and 38% of controls had maternal pesticide exposure in early pregnancy, Dr. Shaw reported at the annual meeting of the Teratology Society. The most common chemical groups to which women had been exposed were poly-alkyl-oxy compounds, glycophosphates, organophosphorus insecticides, alcohols/ethers, and pyrethroids.

However, in adjusted analyses of 52 chemical groups restricted to those for which more than four cases or controls were exposed, only one – the triazine group – was associated with an increased risk of gastroschisis (odds ratio, 1.7), and that association was merely borderline significant, with the confidence interval including unity.

Similarly, in adjusted analyses of 233 individual chemicals restricted to those for which more than four cases or controls were exposed, only two – oxyfluorfen (OR, 1.6) and petroleum distillates (OR, 2.5) – showed an association with this risk; in these cases, the confidence intervals did not include unity.

"We basically got a general lack of association in a discovery, hypothesis-generating study. We have a detailed exposure assessment. ... We conducted many comparisons, and we’ve got modest sample sizes," Dr. Shaw concluded. "And the kicker is that none of the associations we looked at seemed to stand up for young maternal age."

"This is a useful negative study, and it is noteworthy that, even without correcting for multiple comparisons, there were no impressive positive findings," commented session cochair Dr. James Mills, an investigator with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md.

In additional study results, analyses of exposure to those chemicals classified as reproductive toxicants, ones listed in California’s Proposition 65 (which aims to eliminate carcinogenic and teratogenic agents from drinking water and consumer products), and known endocrine disruptors, either alone or in combinations, did not alter the findings, according to Dr. Shaw.

Furthermore, there was no significant association of the combination of pesticide exposure and air pollution exposure (any of either vs. none) and the risk of gastroschisis.

Dr. Shaw had no relevant conflicts of interest.

BELLEVUE, WASH. – Early gestational exposure to agricultural pesticides is only weakly linked to the risk of gastroschisis in offspring, suggests a case-control study conducted in California’s San Joaquin Valley, an area having among the highest levels of pesticide use nationwide.

Using data from the state and the National Birth Defects Prevention Study for the years 1997-2012, investigators led by Gary M. Shaw, Dr.P.H., assessed maternal exposure during early pregnancy to hundreds of chemicals as ascertained from state pesticide reporting data by geographic area and the women’s address of residence, obtained during interviews.

Analyses were based on 156 live births, fetal deaths, or pregnancy terminations affected by gastroschisis and 785 unaffected matched controls.

"Gastroschisis is a rather unique birth defect. It has a very unique epidemiology," noted Dr. Shaw, who is a professor of clinical research and a doctor of public health in the pediatrics department at Stanford (Calif.) University. "It’s one of a few or perhaps the only one that has been increasing around the world for the last 20-30 years, and it really looks like it’s a disease of young women from what we observe." Teenagers, for example, have a seven to nine times higher risk than do older women.

Overall, 35% of cases and 38% of controls had maternal pesticide exposure in early pregnancy, Dr. Shaw reported at the annual meeting of the Teratology Society. The most common chemical groups to which women had been exposed were poly-alkyl-oxy compounds, glycophosphates, organophosphorus insecticides, alcohols/ethers, and pyrethroids.

However, in adjusted analyses of 52 chemical groups restricted to those for which more than four cases or controls were exposed, only one – the triazine group – was associated with an increased risk of gastroschisis (odds ratio, 1.7), and that association was merely borderline significant, with the confidence interval including unity.

Similarly, in adjusted analyses of 233 individual chemicals restricted to those for which more than four cases or controls were exposed, only two – oxyfluorfen (OR, 1.6) and petroleum distillates (OR, 2.5) – showed an association with this risk; in these cases, the confidence intervals did not include unity.

"We basically got a general lack of association in a discovery, hypothesis-generating study. We have a detailed exposure assessment. ... We conducted many comparisons, and we’ve got modest sample sizes," Dr. Shaw concluded. "And the kicker is that none of the associations we looked at seemed to stand up for young maternal age."

"This is a useful negative study, and it is noteworthy that, even without correcting for multiple comparisons, there were no impressive positive findings," commented session cochair Dr. James Mills, an investigator with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md.

In additional study results, analyses of exposure to those chemicals classified as reproductive toxicants, ones listed in California’s Proposition 65 (which aims to eliminate carcinogenic and teratogenic agents from drinking water and consumer products), and known endocrine disruptors, either alone or in combinations, did not alter the findings, according to Dr. Shaw.

Furthermore, there was no significant association of the combination of pesticide exposure and air pollution exposure (any of either vs. none) and the risk of gastroschisis.

Dr. Shaw had no relevant conflicts of interest.

BELLEVUE, WASH. – Many young adults who were exposed to alcohol prenatally have persistent difficulties with math, according to study findings reported at the annual meeting of the Teratology Society.

A team from Emory University in Atlanta performed long-term follow-up with repeated testing of a cohort of infants who were exposed to alcohol when their mothers drank during pregnancy. At the most recent assessment, they had a median age of 23 years; most were African American and of low socioeconomic status.

The study results showed that the young adults who had physical or cognitive effects from their prenatal alcohol exposure had summary math scores that were 10%-11% lower than those in unexposed peers and 3%-4% lower than those in peers who had had childhood disabilities requiring special education.

Detailed testing showed that these affected young adults had difficulty with even simple math skills, such as counting dots and identifying which of two numbers is bigger.

Alcohol-related math dysfunction, including deficits in math achievement as well as in the simple elements that support math functioning, "which one would expect an adult would be quite competent at," persists into adulthood, commented first author Claire D. Coles, Ph.D., professor of psychiatry and behavioral sciences and pediatrics and director of the maternal substance abuse and child development project at Emory.

"Even when compared with other individuals with similar demographic characteristics who have developmental deficits, adults who are alcohol affected demonstrate specific math deficits," she added.

"I believe that alcohol may target neuropsychological functions, like working memory and full-scale IQ, that support math achievement. But I believe there are some other factors involved as well," Dr. Coles said.

Session attendee Dr. Kenneth L. Jones of the University of California, San Diego, asked, "Is this specific enough that you think it could be used as a screen in 5- or 6-year-old children?"

"I think that there is a specific math deficit in kids, yes, and it’s persistent," Dr. Coles replied. "Obviously, there is not a math part of our brain. But I think that whatever it is that alcohol does affects the functions that underlie the ability to do mathematics so that you are going to pick it up regularly in people who are affected."

Session attendee Rajesh C. Miranda, Ph.D., of the Texas A&M Health Science Center in Bryan, asked, "Is it possible to overtrain a person affected by fetal alcohol syndrome to overcome the deficits?"

"We have actually done an intervention program called MILE, which is the Math Interactive Learning Experience, in which we worked with the family and child specifically on remediating these issues. And it seems to be quite effective," Dr. Coles replied. "I’m not saying it magically fixes everything, but it does help with developing some of these underlying factors and improving outcomes."

In the study, the investigators split the alcohol-exposed young adults into three groups: 48 who had physical effects from exposure, 37 who had only cognitive effects from exposure, and 38 who were clinically unaffected by their exposure.

They were compared with each other and with two control groups: 59 unexposed adults matched for socioeconomic status and 54 adults who had had disabilities as children requiring special education.

Scores on a test for math achievement, the Woodcock-Johnson, 3rd edition (WJ-III), showed a significant difference (P less than .01) across the five groups with respect to the broad math (summary) score and with respect to scores for the individual subtests (math calculation, math reasoning, math fluency, applied problems, and quantitative concepts), reported Dr. Coles.

There was a general pattern whereby scores were lower in the young adults prenatally exposed to alcohol who had physical or cognitive effects, compared with all of the other groups.

In a regression model attempting to sort out the factors explaining math performance, significant contributors (P less than .01) included study group, dysmorphic features, working memory, and full-scale IQ.

In addition, scores on the EC301 test of math skills, a standardized test for brain-damaged adults, showed that the group with physical effects of alcohol exposure performed more poorly than all other groups with respect to counting and precise number knowledge. And the groups with physical and cognitive effects performed more poorly than all of the other groups with respect to number comparisons, mental calculations, estimating the results of arithmetic operations, and other measures.

Dr. Coles disclosed no relevant financial conflicts.

BELLEVUE, WASH. – Many young adults who were exposed to alcohol prenatally have persistent difficulties with math, according to study findings reported at the annual meeting of the Teratology Society.

A team from Emory University in Atlanta performed long-term follow-up with repeated testing of a cohort of infants who were exposed to alcohol when their mothers drank during pregnancy. At the most recent assessment, they had a median age of 23 years; most were African American and of low socioeconomic status.

The study results showed that the young adults who had physical or cognitive effects from their prenatal alcohol exposure had summary math scores that were 10%-11% lower than those in unexposed peers and 3%-4% lower than those in peers who had had childhood disabilities requiring special education.

Detailed testing showed that these affected young adults had difficulty with even simple math skills, such as counting dots and identifying which of two numbers is bigger.

Alcohol-related math dysfunction, including deficits in math achievement as well as in the simple elements that support math functioning, "which one would expect an adult would be quite competent at," persists into adulthood, commented first author Claire D. Coles, Ph.D., professor of psychiatry and behavioral sciences and pediatrics and director of the maternal substance abuse and child development project at Emory.

"Even when compared with other individuals with similar demographic characteristics who have developmental deficits, adults who are alcohol affected demonstrate specific math deficits," she added.

"I believe that alcohol may target neuropsychological functions, like working memory and full-scale IQ, that support math achievement. But I believe there are some other factors involved as well," Dr. Coles said.

Session attendee Dr. Kenneth L. Jones of the University of California, San Diego, asked, "Is this specific enough that you think it could be used as a screen in 5- or 6-year-old children?"

"I think that there is a specific math deficit in kids, yes, and it’s persistent," Dr. Coles replied. "Obviously, there is not a math part of our brain. But I think that whatever it is that alcohol does affects the functions that underlie the ability to do mathematics so that you are going to pick it up regularly in people who are affected."

Session attendee Rajesh C. Miranda, Ph.D., of the Texas A&M Health Science Center in Bryan, asked, "Is it possible to overtrain a person affected by fetal alcohol syndrome to overcome the deficits?"

"We have actually done an intervention program called MILE, which is the Math Interactive Learning Experience, in which we worked with the family and child specifically on remediating these issues. And it seems to be quite effective," Dr. Coles replied. "I’m not saying it magically fixes everything, but it does help with developing some of these underlying factors and improving outcomes."

In the study, the investigators split the alcohol-exposed young adults into three groups: 48 who had physical effects from exposure, 37 who had only cognitive effects from exposure, and 38 who were clinically unaffected by their exposure.

They were compared with each other and with two control groups: 59 unexposed adults matched for socioeconomic status and 54 adults who had had disabilities as children requiring special education.

Scores on a test for math achievement, the Woodcock-Johnson, 3rd edition (WJ-III), showed a significant difference (P less than .01) across the five groups with respect to the broad math (summary) score and with respect to scores for the individual subtests (math calculation, math reasoning, math fluency, applied problems, and quantitative concepts), reported Dr. Coles.

There was a general pattern whereby scores were lower in the young adults prenatally exposed to alcohol who had physical or cognitive effects, compared with all of the other groups.

In a regression model attempting to sort out the factors explaining math performance, significant contributors (P less than .01) included study group, dysmorphic features, working memory, and full-scale IQ.

In addition, scores on the EC301 test of math skills, a standardized test for brain-damaged adults, showed that the group with physical effects of alcohol exposure performed more poorly than all other groups with respect to counting and precise number knowledge. And the groups with physical and cognitive effects performed more poorly than all of the other groups with respect to number comparisons, mental calculations, estimating the results of arithmetic operations, and other measures.

Dr. Coles disclosed no relevant financial conflicts.

BELLEVUE, WASH. – Many young adults who were exposed to alcohol prenatally have persistent difficulties with math, according to study findings reported at the annual meeting of the Teratology Society.

A team from Emory University in Atlanta performed long-term follow-up with repeated testing of a cohort of infants who were exposed to alcohol when their mothers drank during pregnancy. At the most recent assessment, they had a median age of 23 years; most were African American and of low socioeconomic status.

The study results showed that the young adults who had physical or cognitive effects from their prenatal alcohol exposure had summary math scores that were 10%-11% lower than those in unexposed peers and 3%-4% lower than those in peers who had had childhood disabilities requiring special education.

Detailed testing showed that these affected young adults had difficulty with even simple math skills, such as counting dots and identifying which of two numbers is bigger.

Alcohol-related math dysfunction, including deficits in math achievement as well as in the simple elements that support math functioning, "which one would expect an adult would be quite competent at," persists into adulthood, commented first author Claire D. Coles, Ph.D., professor of psychiatry and behavioral sciences and pediatrics and director of the maternal substance abuse and child development project at Emory.

"Even when compared with other individuals with similar demographic characteristics who have developmental deficits, adults who are alcohol affected demonstrate specific math deficits," she added.

"I believe that alcohol may target neuropsychological functions, like working memory and full-scale IQ, that support math achievement. But I believe there are some other factors involved as well," Dr. Coles said.

Session attendee Dr. Kenneth L. Jones of the University of California, San Diego, asked, "Is this specific enough that you think it could be used as a screen in 5- or 6-year-old children?"

"I think that there is a specific math deficit in kids, yes, and it’s persistent," Dr. Coles replied. "Obviously, there is not a math part of our brain. But I think that whatever it is that alcohol does affects the functions that underlie the ability to do mathematics so that you are going to pick it up regularly in people who are affected."

Session attendee Rajesh C. Miranda, Ph.D., of the Texas A&M Health Science Center in Bryan, asked, "Is it possible to overtrain a person affected by fetal alcohol syndrome to overcome the deficits?"

"We have actually done an intervention program called MILE, which is the Math Interactive Learning Experience, in which we worked with the family and child specifically on remediating these issues. And it seems to be quite effective," Dr. Coles replied. "I’m not saying it magically fixes everything, but it does help with developing some of these underlying factors and improving outcomes."

In the study, the investigators split the alcohol-exposed young adults into three groups: 48 who had physical effects from exposure, 37 who had only cognitive effects from exposure, and 38 who were clinically unaffected by their exposure.

They were compared with each other and with two control groups: 59 unexposed adults matched for socioeconomic status and 54 adults who had had disabilities as children requiring special education.

Scores on a test for math achievement, the Woodcock-Johnson, 3rd edition (WJ-III), showed a significant difference (P less than .01) across the five groups with respect to the broad math (summary) score and with respect to scores for the individual subtests (math calculation, math reasoning, math fluency, applied problems, and quantitative concepts), reported Dr. Coles.

There was a general pattern whereby scores were lower in the young adults prenatally exposed to alcohol who had physical or cognitive effects, compared with all of the other groups.

In a regression model attempting to sort out the factors explaining math performance, significant contributors (P less than .01) included study group, dysmorphic features, working memory, and full-scale IQ.

In addition, scores on the EC301 test of math skills, a standardized test for brain-damaged adults, showed that the group with physical effects of alcohol exposure performed more poorly than all other groups with respect to counting and precise number knowledge. And the groups with physical and cognitive effects performed more poorly than all of the other groups with respect to number comparisons, mental calculations, estimating the results of arithmetic operations, and other measures.

Dr. Coles disclosed no relevant financial conflicts.

BELLEVUE, WASH. – Women who conceive through noninvasive types of medically assisted reproduction are more likely to have a multiple pregnancy and to give birth to an infant with major congenital malformations, according to a meta-analysis reported at the annual meeting of the Teratology Society.

Investigators led by Sonia Chaabane analyzed study-level data from 58 randomized and nonrandomized controlled trials, cohort studies, and case-control studies published between 1966 and 2013. All assessed ovarian stimulation and/or intrauterine insemination, reported outcomes of multiple pregnancy and/or major congenital malformation, and had a comparison group.

Results showed that compared with natural conception, ovarian stimulation alone increased the risk of multiple pregnancy by 11.68-fold and intrauterine insemination (with or rarely without ovarian stimulation) increased the risk by 9.23-fold.

"This can be explained by the hyperstimulation and multiple follicle development," noted Ms. Chaabane, who is a doctoral candidate in pharmacy at the University of Montreal.

Additionally, ovarian stimulation alone increased the risk of major congenital malformation by 1.14-fold and intrauterine insemination increased the risk by 1.32-fold. All these findings were statistically significant.

When it came to specific types of malformations, ovarian stimulation conferred a higher risk of musculoskeletal; nervous system; gastrointestinal; respiratory system; and eye, ear, face, and neck malformations. And intrauterine insemination conferred a higher risk of musculoskeletal and urogenital malformations.

"The biological mechanisms that can explain the association with major congenital malformations is still unclear," Ms. Chaabane commented. "With increased use of these treatments, other observational studies with a larger sample size and having as primary outcome the risk of adverse events in children would address the weakness in the current studies."

Session attendee Richard Miller, Ph.D., professor of obstetrics and gynecology at the University of Rochester (N.Y.), asked, "In the natural conception control group, were these singleton births? And did these studies try to match up this and other factors, and did you take that into account? Because one of the big problems is that these people are at high risk, that’s why they require [intervention], they are not getting pregnant on their own. So they may have risk factors for bad outcomes that need to be taken into account."

"We used the results obtained from different studies, and in those studies, they maybe adjusted for these risk factors and confounders and maybe not. So we used what we had. And it’s true that many factors, such as multiple birth, are major confounders and risk factors for congenital malformations, for example. When we combined the results, we couldn’t take into account these factors," replied Ms. Chaabane.

However, she added, sensitivity analyses could separate studies reporting unadjusted results and studies reporting adjusted results and determine whether the observed associations differ between these groups.

Ms. Chaabane disclosed no relevant conflicts of interest.

BELLEVUE, WASH. – Women who conceive through noninvasive types of medically assisted reproduction are more likely to have a multiple pregnancy and to give birth to an infant with major congenital malformations, according to a meta-analysis reported at the annual meeting of the Teratology Society.

Investigators led by Sonia Chaabane analyzed study-level data from 58 randomized and nonrandomized controlled trials, cohort studies, and case-control studies published between 1966 and 2013. All assessed ovarian stimulation and/or intrauterine insemination, reported outcomes of multiple pregnancy and/or major congenital malformation, and had a comparison group.

Results showed that compared with natural conception, ovarian stimulation alone increased the risk of multiple pregnancy by 11.68-fold and intrauterine insemination (with or rarely without ovarian stimulation) increased the risk by 9.23-fold.

"This can be explained by the hyperstimulation and multiple follicle development," noted Ms. Chaabane, who is a doctoral candidate in pharmacy at the University of Montreal.

Additionally, ovarian stimulation alone increased the risk of major congenital malformation by 1.14-fold and intrauterine insemination increased the risk by 1.32-fold. All these findings were statistically significant.

When it came to specific types of malformations, ovarian stimulation conferred a higher risk of musculoskeletal; nervous system; gastrointestinal; respiratory system; and eye, ear, face, and neck malformations. And intrauterine insemination conferred a higher risk of musculoskeletal and urogenital malformations.

"The biological mechanisms that can explain the association with major congenital malformations is still unclear," Ms. Chaabane commented. "With increased use of these treatments, other observational studies with a larger sample size and having as primary outcome the risk of adverse events in children would address the weakness in the current studies."

Session attendee Richard Miller, Ph.D., professor of obstetrics and gynecology at the University of Rochester (N.Y.), asked, "In the natural conception control group, were these singleton births? And did these studies try to match up this and other factors, and did you take that into account? Because one of the big problems is that these people are at high risk, that’s why they require [intervention], they are not getting pregnant on their own. So they may have risk factors for bad outcomes that need to be taken into account."

"We used the results obtained from different studies, and in those studies, they maybe adjusted for these risk factors and confounders and maybe not. So we used what we had. And it’s true that many factors, such as multiple birth, are major confounders and risk factors for congenital malformations, for example. When we combined the results, we couldn’t take into account these factors," replied Ms. Chaabane.

However, she added, sensitivity analyses could separate studies reporting unadjusted results and studies reporting adjusted results and determine whether the observed associations differ between these groups.

Ms. Chaabane disclosed no relevant conflicts of interest.

BELLEVUE, WASH. – Women who conceive through noninvasive types of medically assisted reproduction are more likely to have a multiple pregnancy and to give birth to an infant with major congenital malformations, according to a meta-analysis reported at the annual meeting of the Teratology Society.

Investigators led by Sonia Chaabane analyzed study-level data from 58 randomized and nonrandomized controlled trials, cohort studies, and case-control studies published between 1966 and 2013. All assessed ovarian stimulation and/or intrauterine insemination, reported outcomes of multiple pregnancy and/or major congenital malformation, and had a comparison group.

Results showed that compared with natural conception, ovarian stimulation alone increased the risk of multiple pregnancy by 11.68-fold and intrauterine insemination (with or rarely without ovarian stimulation) increased the risk by 9.23-fold.

"This can be explained by the hyperstimulation and multiple follicle development," noted Ms. Chaabane, who is a doctoral candidate in pharmacy at the University of Montreal.

Additionally, ovarian stimulation alone increased the risk of major congenital malformation by 1.14-fold and intrauterine insemination increased the risk by 1.32-fold. All these findings were statistically significant.

When it came to specific types of malformations, ovarian stimulation conferred a higher risk of musculoskeletal; nervous system; gastrointestinal; respiratory system; and eye, ear, face, and neck malformations. And intrauterine insemination conferred a higher risk of musculoskeletal and urogenital malformations.

"The biological mechanisms that can explain the association with major congenital malformations is still unclear," Ms. Chaabane commented. "With increased use of these treatments, other observational studies with a larger sample size and having as primary outcome the risk of adverse events in children would address the weakness in the current studies."

Session attendee Richard Miller, Ph.D., professor of obstetrics and gynecology at the University of Rochester (N.Y.), asked, "In the natural conception control group, were these singleton births? And did these studies try to match up this and other factors, and did you take that into account? Because one of the big problems is that these people are at high risk, that’s why they require [intervention], they are not getting pregnant on their own. So they may have risk factors for bad outcomes that need to be taken into account."

"We used the results obtained from different studies, and in those studies, they maybe adjusted for these risk factors and confounders and maybe not. So we used what we had. And it’s true that many factors, such as multiple birth, are major confounders and risk factors for congenital malformations, for example. When we combined the results, we couldn’t take into account these factors," replied Ms. Chaabane.

However, she added, sensitivity analyses could separate studies reporting unadjusted results and studies reporting adjusted results and determine whether the observed associations differ between these groups.

Ms. Chaabane disclosed no relevant conflicts of interest.

BELLEVUE, WASH. – Louisiana has marked black-white racial disparities when it comes to birth defects, suggests a cohort study of 113,696 live births in the state during 2006-2008.

Relative to peers born to black mothers, infants born to white mothers were 24%-177% more likely to have cardiac, gastrointestinal, and genitourinary defects, according to data reported at the annual meeting of the Teratology Society. But they were 35% less likely to have microcephalus.

"We can conclude from this study that most birth defects are more common in non-Hispanic white children, compared to non-Hispanic black children. We think this difference may be the result of genetic susceptibility or environmental factors that play a significant role," said Dr. Tri Tran, of the department of pediatrics at the Louisiana State University Health Sciences Center and an investigator with the Louisiana Department of Health and Hospitals Office of Public Health children and youth with special health needs program – both in New Orleans.

In the future, the investigators hope to conduct more in-depth study of genetic and environmental factors to determine reasons for the observed disparities, which could help inform effective prevention and intervention strategies, he added.

Session cochair Dr. James Mills, an investigator with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., commented, "I noticed that some of the defects that were more common in whites are things like ASD [atrial septal defect], VSD [ventricular septal defect], PDA [patent ductus arteriosus], and hypospadias, where there may be fairly trivial defects but really good diagnosis. Did you look at the data by socioeconomic class to see if there may be some bias in ascertainment?"

Analyses did not include that potential confounder, Dr. Tran replied.

For the study, the investigators used linked hospital records and data from the Louisiana Birth Defects Monitoring Network, a population-based surveillance system, to identify live births to non-Hispanic white women (57%) and non-Hispanic black women (43%) in which the birth weight was at least 350 g, and the gestational age was at least 20 weeks.

The investigators assessed birth defects captured in the first 3 years of life. Results were restricted to the 19 birth defects seen in at least 30 infants.

In adjusted analyses, infants born to white women were more likely to have ventricular septal defects (prevalence ratio, 1.59), atrial septal defects (1.24), atrioventricular septal defects (1.67), patent ductus arteriosus (1.31), cleft palate without cleft lip (2.20), pyloric stenosis (2.77), obstructive genitourinary defects (1.31), gastroschisis (2.71), Down syndrome (1.49), and hypospadias (1.50).

Only a single birth defect, microcephalus, was significantly less common in infants of white women, compared with infants of black women (prevalence ratio, 0.65), reported Dr. Tran.

Dr. Tran disclosed no relevant conflicts of interest.

BELLEVUE, WASH. – Louisiana has marked black-white racial disparities when it comes to birth defects, suggests a cohort study of 113,696 live births in the state during 2006-2008.

Relative to peers born to black mothers, infants born to white mothers were 24%-177% more likely to have cardiac, gastrointestinal, and genitourinary defects, according to data reported at the annual meeting of the Teratology Society. But they were 35% less likely to have microcephalus.

"We can conclude from this study that most birth defects are more common in non-Hispanic white children, compared to non-Hispanic black children. We think this difference may be the result of genetic susceptibility or environmental factors that play a significant role," said Dr. Tri Tran, of the department of pediatrics at the Louisiana State University Health Sciences Center and an investigator with the Louisiana Department of Health and Hospitals Office of Public Health children and youth with special health needs program – both in New Orleans.

In the future, the investigators hope to conduct more in-depth study of genetic and environmental factors to determine reasons for the observed disparities, which could help inform effective prevention and intervention strategies, he added.

Session cochair Dr. James Mills, an investigator with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., commented, "I noticed that some of the defects that were more common in whites are things like ASD [atrial septal defect], VSD [ventricular septal defect], PDA [patent ductus arteriosus], and hypospadias, where there may be fairly trivial defects but really good diagnosis. Did you look at the data by socioeconomic class to see if there may be some bias in ascertainment?"

Analyses did not include that potential confounder, Dr. Tran replied.

For the study, the investigators used linked hospital records and data from the Louisiana Birth Defects Monitoring Network, a population-based surveillance system, to identify live births to non-Hispanic white women (57%) and non-Hispanic black women (43%) in which the birth weight was at least 350 g, and the gestational age was at least 20 weeks.

The investigators assessed birth defects captured in the first 3 years of life. Results were restricted to the 19 birth defects seen in at least 30 infants.

In adjusted analyses, infants born to white women were more likely to have ventricular septal defects (prevalence ratio, 1.59), atrial septal defects (1.24), atrioventricular septal defects (1.67), patent ductus arteriosus (1.31), cleft palate without cleft lip (2.20), pyloric stenosis (2.77), obstructive genitourinary defects (1.31), gastroschisis (2.71), Down syndrome (1.49), and hypospadias (1.50).

Only a single birth defect, microcephalus, was significantly less common in infants of white women, compared with infants of black women (prevalence ratio, 0.65), reported Dr. Tran.

Dr. Tran disclosed no relevant conflicts of interest.

BELLEVUE, WASH. – Louisiana has marked black-white racial disparities when it comes to birth defects, suggests a cohort study of 113,696 live births in the state during 2006-2008.

Relative to peers born to black mothers, infants born to white mothers were 24%-177% more likely to have cardiac, gastrointestinal, and genitourinary defects, according to data reported at the annual meeting of the Teratology Society. But they were 35% less likely to have microcephalus.

"We can conclude from this study that most birth defects are more common in non-Hispanic white children, compared to non-Hispanic black children. We think this difference may be the result of genetic susceptibility or environmental factors that play a significant role," said Dr. Tri Tran, of the department of pediatrics at the Louisiana State University Health Sciences Center and an investigator with the Louisiana Department of Health and Hospitals Office of Public Health children and youth with special health needs program – both in New Orleans.

In the future, the investigators hope to conduct more in-depth study of genetic and environmental factors to determine reasons for the observed disparities, which could help inform effective prevention and intervention strategies, he added.

Session cochair Dr. James Mills, an investigator with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Md., commented, "I noticed that some of the defects that were more common in whites are things like ASD [atrial septal defect], VSD [ventricular septal defect], PDA [patent ductus arteriosus], and hypospadias, where there may be fairly trivial defects but really good diagnosis. Did you look at the data by socioeconomic class to see if there may be some bias in ascertainment?"

Analyses did not include that potential confounder, Dr. Tran replied.

For the study, the investigators used linked hospital records and data from the Louisiana Birth Defects Monitoring Network, a population-based surveillance system, to identify live births to non-Hispanic white women (57%) and non-Hispanic black women (43%) in which the birth weight was at least 350 g, and the gestational age was at least 20 weeks.

The investigators assessed birth defects captured in the first 3 years of life. Results were restricted to the 19 birth defects seen in at least 30 infants.

In adjusted analyses, infants born to white women were more likely to have ventricular septal defects (prevalence ratio, 1.59), atrial septal defects (1.24), atrioventricular septal defects (1.67), patent ductus arteriosus (1.31), cleft palate without cleft lip (2.20), pyloric stenosis (2.77), obstructive genitourinary defects (1.31), gastroschisis (2.71), Down syndrome (1.49), and hypospadias (1.50).

Only a single birth defect, microcephalus, was significantly less common in infants of white women, compared with infants of black women (prevalence ratio, 0.65), reported Dr. Tran.

Dr. Tran disclosed no relevant conflicts of interest.

BELLEVUE, WASH. – The severity of rheumatoid arthritis early in pregnancy is an independent risk factor for preterm delivery, according to data from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project.

The prospective cohort study of 447 pregnant women with rheumatoid arthritis who had a live-born infant from 2005-2013 found that the greater disease severity before 20 weeks of gestation, assessed by a variety of measures, the higher the adjusted risk of delivering preterm. But there was no significant impact on the adjusted risk of having an infant small for gestational age or a cesarean section.

"Disease severity in women with rheumatoid arthritis, measured early in pregnancy, is predictive of preterm delivery," noted Dr. Balambal Bharti, a researcher at the bioscience center, University of California, San Diego, in presenting the findings at the annual meeting of the Teratology Society.

The investigators are performing additional analyses to determine whether disease severity at different times – early versus late pregnancy – has a similar or differing impact, and to assess any effect of a change in severity during pregnancy.

"For future research, we’d like to investigate if better disease management early in pregnancy improves pregnancy outcome," she said.

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University asked, "Did you know if there were differences in disease severity or treatment based on whether women had planned their pregnancies, and whether that could have affected your results? I’m just wondering if there are certain women who had planned their pregnancy and had changed their treatment regimen in anticipation of that."

"We didn’t know whether women had planned their pregnancies," Dr. Bharti replied, although some data suggest that about half of pregnancies in the Organization of Teratology Information Specialists cohort are unplanned. The investigators also did not look at whether women changed their treatment before conceiving, she said.

Session attendee Dr. Jan M. Freidman of the University of British Columbia in Vancouver noted, "Two of the three outcome variables you looked at are actually continuous variables: birth weight (or birth weight for gestational age) and week of gestation at which you deliver. As a clinician, it would be useful to know what the size of the effect was in terms of those continuous variables: How much did [disease severity] reduce birth weight? How much was the reduction, or was there a reduction, in gestational age? Did you look at the analysis in that way, or just in the discrete way you presented here?"

"All of our outcomes were dichotomized," Dr. Bharti replied.

"There is more information there that you might want to look at," Dr. Friedman recommended.

The women studied were administered the 4-point Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline, before 20 weeks of gestation. They also rated their pain and global health in the past week on 100-point scales.

Overall, 15% of the women had a preterm delivery (one occurring before 37 weeks of gestation), 9% gave birth to an infant who was small for gestational age, and 42% had a cesarean section.

In multivariate adjusted analyses, women’s risk of preterm birth rose with each 1% increase (worsening) in HAQ-DI score (relative risk, 1.55) and with each 20-point increase (worsening) in pain score (RR, 1.17) and score on the global scale of overall health (RR,1.22).

In contrast, none of the three measures of disease severity independently predicted small for gestational age or cesarean delivery.

Dr. Bharti said that, to the authors’ knowledge, only one other prospective study has looked at the impact of rheumatoid arthritis disease severity on pregnancy outcomes (Arthritis Rheum. 2009;60:3196-206). That study followed white Dutch-speaking women in a first pregnancy who were taking prednisone, sulfasalazine, or hydroxychloroquine.

"Our study adds to [that study] by having women of diverse ethnic background who were in a first or subsequent pregnancy, and they were either on no treatment for rheumatoid arthritis or on any kind of treatment," she commented.

The new findings are generally similar to those of that previous study but differ in that they show a positive association between disease severity and preterm delivery, according to Dr. Bharti.

She disclosed no conflicts of interest related to the research.

BELLEVUE, WASH. – The severity of rheumatoid arthritis early in pregnancy is an independent risk factor for preterm delivery, according to data from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project.

The prospective cohort study of 447 pregnant women with rheumatoid arthritis who had a live-born infant from 2005-2013 found that the greater disease severity before 20 weeks of gestation, assessed by a variety of measures, the higher the adjusted risk of delivering preterm. But there was no significant impact on the adjusted risk of having an infant small for gestational age or a cesarean section.

"Disease severity in women with rheumatoid arthritis, measured early in pregnancy, is predictive of preterm delivery," noted Dr. Balambal Bharti, a researcher at the bioscience center, University of California, San Diego, in presenting the findings at the annual meeting of the Teratology Society.

The investigators are performing additional analyses to determine whether disease severity at different times – early versus late pregnancy – has a similar or differing impact, and to assess any effect of a change in severity during pregnancy.

"For future research, we’d like to investigate if better disease management early in pregnancy improves pregnancy outcome," she said.

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University asked, "Did you know if there were differences in disease severity or treatment based on whether women had planned their pregnancies, and whether that could have affected your results? I’m just wondering if there are certain women who had planned their pregnancy and had changed their treatment regimen in anticipation of that."

"We didn’t know whether women had planned their pregnancies," Dr. Bharti replied, although some data suggest that about half of pregnancies in the Organization of Teratology Information Specialists cohort are unplanned. The investigators also did not look at whether women changed their treatment before conceiving, she said.

Session attendee Dr. Jan M. Freidman of the University of British Columbia in Vancouver noted, "Two of the three outcome variables you looked at are actually continuous variables: birth weight (or birth weight for gestational age) and week of gestation at which you deliver. As a clinician, it would be useful to know what the size of the effect was in terms of those continuous variables: How much did [disease severity] reduce birth weight? How much was the reduction, or was there a reduction, in gestational age? Did you look at the analysis in that way, or just in the discrete way you presented here?"

"All of our outcomes were dichotomized," Dr. Bharti replied.

"There is more information there that you might want to look at," Dr. Friedman recommended.

The women studied were administered the 4-point Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline, before 20 weeks of gestation. They also rated their pain and global health in the past week on 100-point scales.

Overall, 15% of the women had a preterm delivery (one occurring before 37 weeks of gestation), 9% gave birth to an infant who was small for gestational age, and 42% had a cesarean section.

In multivariate adjusted analyses, women’s risk of preterm birth rose with each 1% increase (worsening) in HAQ-DI score (relative risk, 1.55) and with each 20-point increase (worsening) in pain score (RR, 1.17) and score on the global scale of overall health (RR,1.22).

In contrast, none of the three measures of disease severity independently predicted small for gestational age or cesarean delivery.

Dr. Bharti said that, to the authors’ knowledge, only one other prospective study has looked at the impact of rheumatoid arthritis disease severity on pregnancy outcomes (Arthritis Rheum. 2009;60:3196-206). That study followed white Dutch-speaking women in a first pregnancy who were taking prednisone, sulfasalazine, or hydroxychloroquine.

"Our study adds to [that study] by having women of diverse ethnic background who were in a first or subsequent pregnancy, and they were either on no treatment for rheumatoid arthritis or on any kind of treatment," she commented.

The new findings are generally similar to those of that previous study but differ in that they show a positive association between disease severity and preterm delivery, according to Dr. Bharti.

She disclosed no conflicts of interest related to the research.

BELLEVUE, WASH. – The severity of rheumatoid arthritis early in pregnancy is an independent risk factor for preterm delivery, according to data from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project.

The prospective cohort study of 447 pregnant women with rheumatoid arthritis who had a live-born infant from 2005-2013 found that the greater disease severity before 20 weeks of gestation, assessed by a variety of measures, the higher the adjusted risk of delivering preterm. But there was no significant impact on the adjusted risk of having an infant small for gestational age or a cesarean section.

"Disease severity in women with rheumatoid arthritis, measured early in pregnancy, is predictive of preterm delivery," noted Dr. Balambal Bharti, a researcher at the bioscience center, University of California, San Diego, in presenting the findings at the annual meeting of the Teratology Society.

The investigators are performing additional analyses to determine whether disease severity at different times – early versus late pregnancy – has a similar or differing impact, and to assess any effect of a change in severity during pregnancy.

"For future research, we’d like to investigate if better disease management early in pregnancy improves pregnancy outcome," she said.

Session cochair Suzan L. Carmichael, Ph.D., of the department of pediatrics (neonatology) at Stanford (Calif.) University asked, "Did you know if there were differences in disease severity or treatment based on whether women had planned their pregnancies, and whether that could have affected your results? I’m just wondering if there are certain women who had planned their pregnancy and had changed their treatment regimen in anticipation of that."

"We didn’t know whether women had planned their pregnancies," Dr. Bharti replied, although some data suggest that about half of pregnancies in the Organization of Teratology Information Specialists cohort are unplanned. The investigators also did not look at whether women changed their treatment before conceiving, she said.

Session attendee Dr. Jan M. Freidman of the University of British Columbia in Vancouver noted, "Two of the three outcome variables you looked at are actually continuous variables: birth weight (or birth weight for gestational age) and week of gestation at which you deliver. As a clinician, it would be useful to know what the size of the effect was in terms of those continuous variables: How much did [disease severity] reduce birth weight? How much was the reduction, or was there a reduction, in gestational age? Did you look at the analysis in that way, or just in the discrete way you presented here?"

"All of our outcomes were dichotomized," Dr. Bharti replied.

"There is more information there that you might want to look at," Dr. Friedman recommended.

The women studied were administered the 4-point Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline, before 20 weeks of gestation. They also rated their pain and global health in the past week on 100-point scales.

Overall, 15% of the women had a preterm delivery (one occurring before 37 weeks of gestation), 9% gave birth to an infant who was small for gestational age, and 42% had a cesarean section.

In multivariate adjusted analyses, women’s risk of preterm birth rose with each 1% increase (worsening) in HAQ-DI score (relative risk, 1.55) and with each 20-point increase (worsening) in pain score (RR, 1.17) and score on the global scale of overall health (RR,1.22).

In contrast, none of the three measures of disease severity independently predicted small for gestational age or cesarean delivery.

Dr. Bharti said that, to the authors’ knowledge, only one other prospective study has looked at the impact of rheumatoid arthritis disease severity on pregnancy outcomes (Arthritis Rheum. 2009;60:3196-206). That study followed white Dutch-speaking women in a first pregnancy who were taking prednisone, sulfasalazine, or hydroxychloroquine.

"Our study adds to [that study] by having women of diverse ethnic background who were in a first or subsequent pregnancy, and they were either on no treatment for rheumatoid arthritis or on any kind of treatment," she commented.

The new findings are generally similar to those of that previous study but differ in that they show a positive association between disease severity and preterm delivery, according to Dr. Bharti.

She disclosed no conflicts of interest related to the research.