Good afternoon or morning or evening, depending on where and when you're listening to this session. I'm Dr. John Iskander. On behalf of CDC, I'd like to welcome you to January's Public Health Grand Rounds. Continuing education credits for Public Health Grand Rounds are available for physicians, nurses, pharmacists, health educators, and other health professionals. Please see more at the Grand Rounds website.
Grand Rounds is also available on all of your favorite web and social media sites. We have a featured video segment on YouTube called Beyond the Data, which is posted shortly after the session. We're also live tweeting today, so please use hashtag CDC Grand Rounds for all your tweeting needs.
We're happy to help share in the observance of January, which is National Birth Defects Prevention Month. The theme for this year is making healthy choices to prevent birth defects by making a pact for prevention. New and ongoing research can be located in current and upcoming MMWR articles, as well as through expanded access to state-level data at the websites listed here.
So it's now awards season in the entertainment industry. I'm happy to recognize today's stars, as well as the numerous talented individuals listed here who have contributed to this session. I'd like to give a special acknowledgement to Peggy Honine and Regina Simeone.
We've partnered with the CDC Public Health Library and Information Center to feature scientific articles relevant to this session. The full listing is available at CDC.gov slash scienceclips. For those of you who turned in last month to our session on climate change and health, we wanted to share these key late-breaking data points with you. 2014 was, again, the hottest year on record.
Here's a preview of upcoming Grand Rounds session. Please join us live or on the web at your convenience. It's now my pleasure to introduce Dr. Ileana Arias, Principal Deputy Director of CDC. Thank you, Dr. Arias, for joining us. Good afternoon and welcome to today's very important and important for us Grand Rounds.
About one in 33 babies is born with a birth defect in the United States. That means that every year about 120,000 babies... are born with a birth defect. And as was pointed out in the video, that means that every four and a half minutes we have a baby born in this country with a birth defect.
That's unacceptable. Birth defects can occur. in any family regardless of race, health history, economic status, and level of education. We know that most birth defects develop during the first weeks of pregnancy, which is critically important to recognize because that means that planning for a pregnancy and taking steps before pregnancy is incredibly important for primary prevention.
Unfortunately, we also know that not all birth defects are birth defects can be prevented. But we do know that there are some actions that can be taken before pregnancy to increase a woman's chance of having a healthy baby. For example, two of the most important ones are quitting smoking and taking a folate supplement. It is something that we have known for a while. It is something that we have communicated widely.
It's something that many of us have heard. And although it may seem obvious to many of us, we know that still one out of ten women still smoke sometime during pregnancy. We know that's true.
some medications can cause birth defects and we are working to determine which alternatives might be safer to use during pregnancy. It's not only about personal choices that individual women can make in order to prevent birth defects. We have begun to identify some critical and common environmental exposures that increase women's risk of having a child born with a birth defect.
And further, we are seeking to better understand other less common but equally impactful. exposures. With our partners, we're working together to identify the causes of birth defects and importantly to find opportunities for preventing them and improving the health of individuals of all ages living with health defects. We're also committed to broadly communicating established prevention science to health care providers and the public so that they can act to protect.
patients and themselves using events such as the public health ground rounds today. Today we are going to hear how public health experts are furthering our understanding of the causes of major birth defects, their impact on our communities, and especially important, what it is that we can do to help ensure safe and healthy pregnancies for all women. I would like to thank all of our presenters today and welcome them to Atlanta, our visitors, and look forward to the wonderful presentations that we're about to hear.
Our first speaker today is Dr. Marcia Feldkamp. Thank you and good afternoon. The children you see here and throughout this session are featured in a powerful video involving Utah parents and their children with birth defects in collaboration with the Parent Advisory Group of the National Birth Defects Prevention Network.
I will talk briefly about the impact of birth defects and our current understanding of their causes. The term birth defect, also known as congenital anomaly or congenital malformation, is an abnormality affecting body structure or function that is present at birth. A birth defect may be clinically obvious at birth or may be diagnosed in infancy. childhood, or later in life.
There are two main categories of birth defects. First are functional defects. These include developmental disabilities, such as cerebral palsy or deafness, metabolic conditions, such as PKU, or or hematologic diseases such as sickle cell. And second are structural defects, which are divided into two groups, major and minor malformations. Major malformations include any structural abnormality with surgical, medical, or cosmetic importance, whereas minor birth defects are those structural abnormalities without any surgical, cosmetic, or medical situations.
So today we're going to be talking about talking about major malformations. Major birth defects, as was mentioned, are common, occurring in one of every 33 babies, or 3% of births, resulting in an estimated 120,000 affected babies per year in the United States. By five years of age, one in 20 children will be diagnosed with a birth defect.
As shown here, congenital heart defects represent the largest group of birth defects, approximately one quarter of all birth defects. This figure shows three different hearts. On the left is an image of a normal heart.
In the center, this figure illustrates hypoplastic left heart syndrome, and on the right, transposition of the great arteries. Heart defects vary in their level of severity. Both of these congenital heart defects would require surgery in the first year of an infant's life.
Neural tube defects such as spina bifida and anencephaly, shown in this slide, are birth defects affecting the brain and the spinal cord that occur very early in pregnancy. Babies born with anencephaly do not survive, whereas babies born with spina bifida survive with mild to severe disabilities, depending on the severity of the defect. Serious birth defects of the abdominal wall include two main types.
On your left is gastroschisis, where at birth the intestines and and sometimes other organs are actually outside of the abdominal cavity through an opening in the abdominal wall, usually on the right side of the umbilical cord, and are not covered by any membrane. On your right is a fallacy, where organs are actually outside of the abdomen, but they are covered by a membrane. Birth defects are costly. They are the leading cause of pediatric hospitalizations and medical expenditures.
This figure shows the average daily hospital charges per... newborn based on the average length of stay and the average medical charges for an uncomplicated birth represented by an infant without a birth defect at the top of the figure compared to ten different types of birth defects however it is important to keep in mind that these charges do not reflect the medical cost to the family after the newborn period Based on 2004 data, an estimated 2.6 billion U.S. dollars are spent annually to care for infants, children, and adults with a birth defect. Medical care and technology have improved the long-term survival of children born with birth defects. Other costs that are more difficult to measure include the financial impact when only one parent is able to work, or a parent's missed days at work to care for a child, or the impact on other children within the family.
We do not understand... the cost to both the child affected with a birth effect and their family's emotional well-being. These associated costs across the lifespan of a baby born with a birth effect are important and require more research.
Birth defects are critical, representing the leading cause of infant mortality. For every 1,000 babies born in the U.S. in 2011, seven died during their first year of life. Of these, 20% or about one in every five infant deaths will be due to a birth defect.
Again, congenital heart defects represent the largest birth defect group among infant deaths. Birth effect related infant mortality was higher than causes of death related to low birth weight or prematurity, maternal factors, sudden infant death, or accidents. The causes of birth defects are considered complex, with both genetic and environmental factors playing a role. We know that birth defects occur early in pregnancy, often before a woman knows she's pregnant. For most birth defects, there is a critical time period in organ development when these occur.
The process for many of these organs are likely patterned during the first 14 days after conception. As early as 14 days after conception, the brain, spinal cord, heart, circulatory, and digestive systems begin to develop. Most organ development is completed by 8 weeks gestation, but some are completed a couple of weeks later, and others, such as the brain, continue to develop throughout the pregnancy. Because organ development begins after conception, the critical time period for all women to reduce their risk is before they become pregnant.
For example, in order to reduce risk of neural tube defects, a woman must consume folic acid prior to conception. The neural tube begins to close at 14 days post-conception and is completed by 28 days. Folic acid fortification of cereal and grain products has been a very effective strategy because it increases folate levels among all women in the United States, whether planning a pregnancy or not. However, because women may not consume enough fortified grains each day, it is important for women in their childbearing years to take a multivitamin with folic acid. Monitoring the prevalence of birth defects is important to understand whether any are increasing over time.
Based on prevalence data from 15 states during an 11-year period, The overall prevalence of gastroschisis has increased. Mothers younger than 20 years of age show the greatest increase over time. This well-documented increase in gastroschisis suggests that one or more factors are increasing in the environment. Continuing to investigate environmental factors is very important.
Though great advances have been made to improve medical care among children born with birth defects, we still do not understand the cause of the majority of birth defects. In Utah, we recently completed a study based on data from the population-based statewide surveillance system for major birth defects. From 2005 to 2009, 6,500 cases were re-reviewed, representing an overall percentage of major birth defects in Utah at 2.1%. This figure is lower than expected because not all major birth defects were monitored during the time period.
Among these, 77% of babies born with at least one major birth defect did not have an identifiable cause. Less than 1% of the cases were due to a known teratogen, the greatest proportion due to maternal pre-gestational diabetes. These data are broadly compatible with a previously published study in 1989 by Nelson and Holmes. Because the most recent data suggests that the majority of birth defects do not have an identifiable cause, our work must focus on these 77% of babies born with a birth defect.
To do this, we must systematically monitor all major birth defects occurring in the United States to understand their frequency and whether or not they are increasing in the population. We must also investigate both the modifiable and the non-modifiable environmental factors to which women are exposed. Birth defects are common, Costly and critical. Children and their families deserve our utmost attention to improve our understanding of birth defects so we may help to reduce the risk for all and improve lives. Thank you.
Our next speaker is Dr. Yanita Rafehouse. Good afternoon. Today I will talk to you about CDC-funded case control studies of birth defects.
You can study rare outcomes such as birth defects using cohort studies, which will provide prospective exposure information, but you would need a very large and a very expensive study to ascertain sufficient cases. Doing data linkage studies is cost efficient, however, creating the mother-baby linkage can be challenging, and the diagnostic information is not always sufficient. Pregnancy registries are useful for identifying major effects of medications and to point us in a certain direction, but are not population-based. Case control studies are efficient and often contain high quality diagnostic data, giving us the power to look at the specific birth defects instead of birth defects overall.
The challenge is that the annual number of specific cases is small, requiring many years of data, and with retrospective exposure ascertainment, there is the potential for recall bias. The National Birth Defects Prevention Study, or NBDPS, is a population-based case control study of birth defects that included births from October 1997 through December 2011. Cases were identified from state-based birth defect surveillance systems in 10 states across the US. The total birth population in the study cohort during this period was approximately 6 million births. More than 48,000 case pregnancies were identified.
Case pregnancies had at least one of the more than 30 included defects. and life-borne controls were ascertained from birth hospitals or vital records. Mothers participated in a telephone interview, in English or Spanish, on a range of topics and more than 44,000 women were interviewed. Buckle cell swabs were requested for the mother, father and infant. MBDP-S so far has resulted in more than 200 peer-reviewed manuscripts and I want to describe some of the results.
Data from the MBDPS confirmed the association between pre-gestational diabetes and heart defects, with an overall odds ratio of 4.6. But also for non-heart defects, we observed elevated odds ratios. We also started asking about stressful life events in 2006, and first data do indicate there may be an association between neural tube defects and having several stressful life events during pregnancy, and a possible protective effect if you feel you have a good support system.
Over one-third of the papers so far have assessed medications during early pregnancy. One example is opioid medications and birth defects, where MBDPS data confirmed an association with heart defects, such as hypoplastic left heart syndrome, and also identified associations with spina bifida, gastroschisis, and some other defects. Often, maternal disease in pregnancy needs to be treated.
Treating fevers, for instance, is important, as studies have shown fever to be associated with some birth defects. But it is important to do a risk-benefit assessment of medications during pregnancy to ensure the benefits outweigh the risks. One of our goals is to describe birth defect risks of different medications for specific diseases to offer women and their health care providers guidance on treatment options.
We have looked in MBDPS at different SSRIs and the defects associated with them, as well as antibacterials used by women who reported a urinary tract infection, and both papers offer information on a number of different treatments. To use antibacterials as an example, Kreider and colleagues wanted to estimate the association between specific classes of antibacterials and selected birth defects. Here I'm presenting some of the results, looking at specific groups of birth defects and different classes of antibacterials. You can see that the association between an antibiotic class and a birth defect differs with each birth defect and medication class. One approach that the Birth Effect Branch, together with its partners, has taken is the Treating for Two initiative, which has three focus areas, which address its key aims.
Better research, reliable guidance, and informed decisions. We aim to expand research to fill knowledge gaps, to evaluate evidence to develop reliable guidance, and to deliver information to support decision-making among prescribers, pharmacists, and patients and consumers. We really wanted to continue to explore modifiable risk factors such as medications. There is a continued need for post-licensure research into medications because pregnant women are not included in pre-marketing medication trials for new medications, which are constantly introduced.
In addition, existing medication could be used for new indications. An example is the anti-epileptic topiramate, which has been associated with cleft lip, which is now part of a weight loss medication. Now we know that obesity is also associated with birth defects, so that required some careful consideration. Another example is the fact that anti-epileptics are now also used to treat migraines, so the frequency with which some of these medications are used is increasing, and knowing the dose has gotten more important since different indications require different doses.
The changes were extensive enough to warrant a new name, the Birth Defects Study to Evaluate Pregnancy Exposures, or BD-STEPPS. We reduced the number of included defects to 17 by focusing on severe defects that are more common, to have a larger public health impact, and defects that are consistently ascertained across study sites. BD-STEPPS is a collaboration between seven centers.
We started BD-STEPPS with births starting on January 1, 2014. And for BD Steps, we will focus our questions on the first trimester of pregnancy. Another area we are focusing on in BD Steps is maternal chronic disease. We wanted to explore how many mothers of babies with birth defects are cancer survivors or have undergone organ or tissue transplants.
The numbers are going to be small, but we would like to start describing how many women report this. We also want to focus on some maternal diseases with increasing prevalence, such as asthma and ADHD. Asthma is a disease we are interested in since the prevalence of asthma has increased, especially among women, and in the MDPS we saw some evidence of associations between asthma medications and birth defects.
We are also obtaining more detail on the diagnosis and treatment of diabetes and mental health disorders, such as depression. For all our findings, it is important that they get replicated. After all, this is epidemiological research, so confirmation in an independent study sample is needed.
But for instance, we do now know that smoking causes orophacial clefts. Therefore, we need to continue smoking cessation programs focused on reproductive age women. Other known risk factors for birth defects include isotretinoin, a treatment for acne, and thalidomide, which is available to treat multiple myeloma.
And we see more and more statistical modeling studies, which allow us to assess the impact we can have by eliminating an unnecessary exposure, such as smoking, or substituting one medication with another. As you think through these associations and how they might affect your patients or your family, it is very important to remember that one in 33 pregnancies are affected by birth defects. CDC's birth defect branch and its collaborators will continue to contribute to identifying risk factors for birth defects and really focus on clarifying the risk-benefit of medications and whether safer treatment options might be available.
Thank you. Our next speaker is Dr. Alan Mitchell. Good afternoon.
Today I am speaking on behalf of the Vaccines and Medications in Pregnancy Surveillance System or VAMPS. Over the past four decades exposure to medications in pregnancy has been increasing both in terms of the mean number taken by, excuse me, a mean number of pregnant women taking any medication and the proportion of women taking four or more medications at a at any time or in the first trimester of pregnancy. Medications whose use in pregnancy has increased in recent years include selective serotonin reuptake inhibitors and attention deficit hyperactivity disorder medications.
primarily the mixed amphetamine salts. While these trends are important markers of drugs that warrant particular attention, our focus is on preparedness and how we can monitor safety during widespread uptake of vaccines or medications in response to a public health emergency. For the purposes of birth defects prevention, we need to focus on medications and vaccines for which trends document increasing use in pregnant women and where pregnancy Exposure is common, but data on pregnancy risk and safety are insufficient.
The safety of medications and vaccinations in pregnancy is largely unknown because, as has been pointed out, pregnant women are typically excluded from clinical trials conducted prior to marketing. The contribution of medications and vaccines to adverse pregnancy events, such as birth defects, is unknown. However, use of medications and vaccines that may be harmful to pregnant women is not known. during pregnancy is usually avoidable.
Since 2004, the CDC Advisory Committee has recommended that pregnant women receive influenza vaccine regardless of trimester. Just like any other widely used exposure, safety must be monitored. Data from the VAMS program, about which you'll hear more shortly, show the prevalence of exposure to any type of influenza vaccine during pregnancy by year of last menstrual period.
Thank you. Prevalence of exposure to any flu shot has increased steadily since 2005, with 18% of pregnant women exposed in that year and 54% of women exposed in 2013. The exception was a large increase in uptake in response to the 2009-2010 PH1N1 influenza pandemic. Again from the VAMPS data, use of anti-influenza antivirals also increased during the pandemic in 2009-2010. Given antigen adrift that has been observed in the predominant influenza A.H.3N2 subtype this season, and concerns that this may reduce the effectiveness of the vaccine, we may well see increased use of influenza antivirals for the 2014-15 season.
Vaccination in pregnancy is now recommended to prevent other illnesses, such as pertussis in the offspring. Along with increased reporting of pertussis outbreaks, since 2011 there has been a corresponding increase in acellular pertussis use among pregnant women. In order to learn about the risks and relative safety in pregnancy of new exposures, such as vaccines, drugs, and biologics, we need to have a system in place. that is agile in its ability to identify and study new products. The Vaccines and Medications in Pregnancy Surveillance System, or VAMPS, is a unique system that was designed specifically to assess the risks and safety of vaccines and medications that are used in pregnancy.
There is a particular focus on those vaccines and medications that are newly introduced into the pregnant population. Funding from VAMPS comes from both federal sources, including CDC, and pharmaceutical manufacturers. Funders are not directly involved in the conduct of VAMPS studies.
VAMPS is able to identify the wide range of relatively common adverse pregnancy outcomes. Importantly, it also has the power to evaluate specific birth defects. VAMPS targets new and old drugs and vaccines that are recommended for use in pregnancy or that may come into use during pregnancy.
These include products being used for purposes or in populations other than those for which they were approved, including use in pregnant women. Among vaccines currently recommended for use in pregnancy are annual influenza vaccines and Tdap. Future examples will likely include RSV and Group B strep vaccines. Should an Ebola vaccine be marketed, it would easily be included under vamp surveillance.
Of critical importance, VAMPS can direct focus on new exposures within only several months'time. Sorry. VAMPS is a collaboration among the American Academy of Asthma, Allergy, and Immunology and two research arms. A pregnancy cohort operated by the Organization of Teratology Information Specialists Research Center at the University of California, San Diego. and a case control study operated by our Sloan Epidemiology Center at Boston University.
It also includes an independent advisory committee comprised of members from the CDC, National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the American Congress of Obstetricians and Gynecologists, the American Academy of Pediatrics, a biostatistician, and a consumer representative. The committee reviews the accumulating data at periodic intervals and provides suggestions and guidance for analysis and interpretation. Additionally, the advisory committee helps to assure rigor and independence of data monitoring. Of the two research arms, OTIS provides the prospective cohort.
It is a North American wide network of university or hospital based services in existence since 1979. Specialists provide risk counseling to 80 to 100,000 pregnant women and health care providers each year. The network can screen callers from a geographically diverse area to identify those exposed to a vaccine or medication of interest, along with an unexposed comparison group. ODIS sites ascertain and refer potential participants to a coordinating center. Three cohorts are concurrently recruited. An exposed cohort, a disease-matched cohort, and a healthy unexposed cohort.
Each cohort is followed for birth defects overall, preterm birth, growth, and spontaneous abortion. All three groups receive multiple maternal structured telephone interviews at standard time points. In addition to an outcome interview, women's medical records are reviewed.
In some studies, specialized physical examination and developmental follow-up are conducted. Maternal interviews and medical records review provide detailed information on dose, timing, duration of medication, and vaccine exposure as coded by the Sloan Drug Dictionary, maternal disease or indication for medication, pregnancy history, health history, and demographic factors, and importantly, a wide range of potential confounders, including other prescription or over-the-counter medications, body mass index, tobacco, alcohol, and vitamin and mineral use. The other research arm is case control surveillance provided by the birth effects study initiated in 1976 at the Sloan Epidemiology Center. Its objectives are to identify risks and safety of the wide range of medications and vaccines with respect to the wide range of specific birth defects, to establish ranges of safety for various specific medications, and to identify rates of exposure to specific agents. Case infants are infants born with specific major malformations.
Control infants are those born without malformations. The BDS is a multi-center study with centers including surveillance of selected hospitals in greater metropolitan Boston, Philadelphia, San Diego, and Nashville. It also includes state birth defect registries in Massachusetts and New York State. Mothers are interviewed within six months of delivery by trained study nurses. Interviews are conducted by phone using a computer-assisted telephone interview.
Data collected in the interview include demographic and reproductive factors such as age, education, occupation, and parity, medical history, use of any and all prescription and over-the-counter medications, vaccines, vitamins and minerals, supplements. All of these are coded, again, by the Sloan Drug Dictionary, making a common coding platform. Indication for use of each drug is also captured.
In addition to these factors, the interview elicits information on a wide range of potential confounders such as smoking, alcohol, and diet. VAMPS has conducted studies examining vaccine risk during the pandemic H1N1 influenza response. Anticipating a pandemic caused by H1N1 influenza and the widespread exposure to the influenza vaccine in 2009-10 among pregnant women, The Biomedical Advanced Research and Development Authority, or BARDA, a part of DHHS, requested that VAMPS monitor the risks and relative safety of the pandemic H1N1 vaccine and anti-influenza antiviral drugs.
VAMPS was able to quickly modify data collection to meet this objective. Of note, any major signal indicating a safety concern for a particular birth defect. would likely have been detected prior to the first presentation of data to the VAMS Advisory Committee which occurred only a few months after the completion of the season.
The cohort arm considered many adverse outcomes. For birth defects in the aggregate, it found no evidence of an increased risk. The case control arm with power to consider risks related to specific birth defects found no evidence of risk for virtually all defect study, and for some, the estimates were sufficiently stable to suggest evidence of relative safety. We don't know which infectious threat will emerge next.
Pregnant women may be at high risk for disease complications which endanger their pregnancies. Drugs, vaccines, or other medical products might be used in pregnant women with little or no prior study. VAMS has proven to work in monitoring safety of emergency countermeasures in pregnant women and on short notice.
VAMS represents a key tool to maintain confidence among providers and the public alike that preventive measures are indeed being monitored. Thank you, and our final speaker is Suzanne Gilboa. Good afternoon. I will be sharing with you one clear success story about the prevention of birth defects as well as some of our current work to estimate the impact that we might be able to have in the future. The story of folic acid fortification to prevent neural tube defects is considered a huge public health achievement.
Randomized control trials and observational studies demonstrated folic acid intake during early pregnancy could protect against neural tube defects in the developing embryo. Based on this knowledge, in 1992, the United States Public Health Service issued a recommendation that all women of childbearing potential consume 400 micrograms of folic acid daily. In 1998, enriched cereal grain products were required to be fortified at 140 micrograms per 100 grams, and ready-to-eat cereals were allowed to be fortified up to 400 micrograms per serving.
Immediately following mandatory fortification, the birth prevalence of neural tube defects declined. Using data through 2011, we estimated that folic acid fortification in the United States prevents neural tube defects in about 1,300 births each year, for a combined total of about 15,000 prevented since 1999, as shown by the shaded area. This has resulted in direct savings of over $4.7 billion.
Folic acid fortification and the prevention of neural tube defects was a public health home run and showed that we could have an impact on birth defects. We have used mathematical modeling of other risk factors for birth defects to see where we might have a further impact. In the next several slides, I will describe a basic method, as well as the data inputs and results from modeling exercises focused on maternal pre-pregnancy obesity, pre-gestational diabetes, and smoking. Our basic approach is a three-step process. First, we assemble our data inputs.
These inputs are the prevalence of the risk factor among pregnant women and women of reproductive age from national surveys, the prevalence of birth defects under consideration from national estimates from the National Birth Defects Prevention Network or from the Metropolitan Atlanta Congenital Defects Program, and the magnitude of the association between the risk factor and birth defects, generally from published meta-analyses. Sometimes, as in the pre-gestational diabetes example, We needed to conduct our own meta-analyses to come up with a summary measure of association. Then, we estimate the population attributable fraction, or the proportion of birth defects in the population that are attributable to that given risk factor.
Finally, we estimate the number of preventable cases of the birth defect if that risk factor were eliminated or had a reduced impact. We use statistical methods to be able to adequately incorporate the uncertainty in our input parameters. The first example I'm going to talk about is obesity.
The map on the left displays the percentage of each state's population that was classified as obese in 1990 based on self-reported height and weight in the Behavioral Risk Factor Surveillance Survey. Notice that no state had more than 14 percent of their population considered obese. Twenty years later, this is the picture on the right, with no state having less than 20 percent of their population obese. Estimates of the prevalence of pre-pregnancy obesity vary widely, depending on which published literature you look at.
For example, based on the Pregnancy Risk Assessment Monitoring System, the prevalence of pre-pregnancy obesity is about 18.7%. Based on measured data on height and weight from the National Health and Nutrition Examination Survey, 33% of women were classified as obese. Whereas, based on self-reported height and weight in BRFSS, 20% of women 20 years of age or older were classified as such. This is confusing and creates uncertainty.
For our model, we started with the PRAMS estimate of 18.7% and created a bias factor using the other two data sources to adjust for the under-reporting of obesity. And these are the additional input data used to model the public health impact of pre-pregnancy obesity on birth defects. In the first column are selected birth defects, congenital heart defects, spina bifida, and cleft lip with or without cleft palate.
In the second column are the odds ratios representing the magnitudes of the associations between pre-pregnancy obesity and each of the birth defects. In the third column are the estimates of the prevalence of each of these birth defects per 10,000 births. And the fourth column are the estimated annual number of children born with each birth defect calculated by multiplying the prevalence by the total number of live births in the US, approximately 4 million. The percent of cases in the population estimated to be caused by pre-pregnancy obesity are here in column 2, with the highest attributable fraction of 28% for spina bifida. The next two columns show the annual preventable number of cases of each defect for two different scenarios, one with the elimination of pre-pregnancy obesity, and the other with a 10% reduction in the risk associated with pre-pregnancy obesity.
Because congenital heart defects are more common, elimination of pre-pregnancy obesity would have the greatest impact there. with 2,850 cases of congenital heart defects averted. With a more modest 10% reduction, we could expect that 285 congenital heart defects could be prevented each year. For other defects, the potential impact is smaller, with approximately 400 cases of spina bifida and 260 cases of cleft lip with or without cleft palate averted. The second example I will talk about is pre-gestational diabetes.
The prevalence of type 1 and type 2 diabetes has increased in the U.S. among individuals of all ages. Among women of reproductive age, estimates vary between 1.9 and 4%, as an additional one-half to 1% of reproductive age women with diabetes have not been diagnosed. For the modeling of the impact of diabetes on birth defects, we used the race-ethnicity-specific prevalences of diabetes among women aged 20 to 44 from NHANES.
And these are the rest of the data inputs that we used to model the impact of maternal diabetes control on the prevalence of congenital heart defects. For presentation purposes, I am focusing on only a few of the many heart defects that were included. In the second column are the summary odds ratios for the associations between pre-gestational diabetes and these heart defects. These were derived from a meta-analysis that we conducted following an extensive systematic review of the literature.
The third column are the estimated prevalences of congenital heart defects, and the last column are the estimated annual number of children born with each heart defect. In column two, we have the population attributable fractions, which range from 7.9% for coarctation of the aorta to 14.8% for tetralogy of Fallot. The next two columns show the annual preventable number of cases of each heart defect, first under the scenario of the elimination of the risk associated with pre-gestational diabetes, or essentially the scenario in which all women with pre-gestational diabetes were under perfect blood sugar control. We estimated that approximately 2,670 cases of congenital heart defects could be averted each year if women with pre-gestational diabetes were under perfect blood sugar control.
The estimates for the specific congenital heart defects listed ranged from 75 per year to 230 per year. Under the scenario of a 50% reduction in risk associated with pre-gestational diabetes, We estimated 1,335 children would be born without a congenital heart defect. With respect to pre-gestational diabetes, we have also estimated the impact on costs. In a different modeling analysis, we estimated the birth defects associated costs that could be averted if universal preconception care for women with either diagnosed or undiagnosed pre-gestational diabetes were in place.
We again used inputs from NHANES on the prevalence of diagnosed and undiagnosed diabetes among women of reproductive age. We also used a published meta-analysis with estimates of the prevalence of birth defects among women with untreated predestinational diabetes, as well as the effectiveness of preconception care to reduce the risk of birth defects due to diabetes. And finally, we used estimates of the lifetime cost in 2012 dollars of birth defects, including medical care and other services, and lost productivity. The modeling study estimated that there would be approximately 4,730 birth effects averted each year and $1.9 billion in lifetime costs.
The last example I will talk about is smoking. The release in January 2014 of the 50th anniversary Surgeon General's report on the health consequences of smoking was landmark for its recognition of smoking during early pregnancy as a cause of oral facial clefts. Smoking during pregnancy is one of the few known risk factors for oral facial clefts with a potential for prevention. Even with widespread knowledge of the hazards of smoking, according to data from PRAMS, nearly one-fourth of women smoke just before pregnancy.
We modeled the impact of smoking cessation on oral facial clefts. These are the input data that were used for the smoking and oral clefts study. We used the summary odds ratio from a recent meta-analysis of smoking and oral facial clefts of 1.28.
The results of the smoking modeling estimated a population attributable fraction of just over 6%, and approximately 430 oral facial clefts preventable each year with cessation of smoking just before pregnancy. As Dr. Feldkamp discussed earlier, birth defects are common, costly, and critical. And despite our work, the majority of birth defects still do not have an identifiable cause.
The causes of most birth defects are likely to be multifactorial. a complex interaction between genetic predispositions and modifiable risk factors. However, considering the modeling that we have done using recognized modifiable risk factors for birth defects, we know that we can have an impact on prevention. Thank you for your time, and we will be happy to take your questions.
You're asked to keep your questions brief. How many states participate and how are they funded or supported? Yes, approximately over 40 states in the United States do have birth defect surveillance systems.
They're funded through a variety of modalities. CDC currently funds 14 of those states. States also receive funds through MCH Title V funding as well as their state general funds. But each state has its own system. Hi, I'm Godfrey Oakley from Emory.
Thank you very much for lovely presentations. I would just like to, sometimes people think birth defects are just developed country diseases, and people now want to lower the... perinatal mortality to 10 in every country in the world, we need to remember that if we don't prevent the birth defects in every country in the world, we will never reach that perinatal objective.
And you've done a nice thing of laying out things that can be prevented. And they can be prevented here, and they can be prevented all over the world. Good afternoon, and thank you for wonderful presentations.
Marsha, you showed a concerning slide about gastroschisis in very young women, and I'm wondering what's being done to address that concern. There is a lot of interest around the world trying to figure out why young women are at the greatest risk. We still don't know.
It's definitely unique to gastroschisis. Some of us are looking at infection and inflammation as a possible cause. cause but we don't know they're certainly known to have more risky behaviors Again, from our online audiences, what is the state of the science about trichloroethylene as an industrial solvent or dry cleaning fluid and fetal heart defects?
Are there resources available for patient community education about TCE and birth defects? So using the MBDP, in the MBDPs we ask mothers where they work and so that is one avenue that we're exploring to identify exposures during during early pregnancy and the solvents are definitely a class that we include in that. In addition for the MBDPS, we're also geocoding.
And so one of the projects we would at some point like to do perhaps is to actually actually look at locations of different exposures. Back when I worked at Nage, we were talking about women that lived close to dry cleaning places to see if that might be something to pursue. Almost a follow-on question again from online audiences.
Is anyone studying the relationship between community environmental exposures to hazardous substances and birth defects? Again TCE is mentioned in living and work spaces pesticides drifting into residential areas, et cetera? Yes. So in the MBDPs, we are, there have been papers published using MBDPs data. So far they have been from one of our sites and it hasn't been collaborative across because the, as you might imagine, the exposures in the different sites are very different whether you're dealing with a rural area such as the San Fernando Valley in California.
or you're dealing with metropolitan Atlanta where we are right now. So we are looking into trying to link our location information of where moms lived during pregnancy, during early pregnancy, to possible environmental exposures. So, could you clarify for me about neural tube defects? So, in 98 and 99, as was pointed out, we got FDA to agree to fortify.
I'm wondering if there is information on what's been going on in terms of women's consumption of folic acid. Particularly it's of more interest to since there is an obesity epidemic that has come up and as you pointed out there's an impact of obesity on spina bifida. So could you just talk a little bit about some of those, elaborate on those issues for me?
Our data on consumption of folic acid supplements shows that most women take a folic acid supplement later during pregnancy, but only approximately 20% to 30% are taking it during early pregnancy. So... So those messages about taking a supplement have not been as effective as to getting women to take it during the time that we would love them to be taking it.
But yes, you're right, there's competing risk and protective factors at the same time. So and there's data to suggest that obese women may need to take more folic acid if they're not, if they're unable to absorb as much folic acid as a non-obese woman in terms of having the appropriate protective effect. I also want to... last week's or actually this past Thursday's MMWR also has some interesting studies about the consumption of folic acid in neural tube defects.
I think that's first trimester. Thank you very much for all these presentations that were incredibly great and of course my favorite part always is the section on what would happen if. So given that I was wondering if you could comment on what are the implications for action either on our part or in collaboration with our partners of the results of the modeling that you've been conducting. I think the probably our most fruitful path is going to be preconception care with respect to diabetes control and that that's a huge risk factor for birth defects especially congenital heart defects and I think we can probably have our greatest impact there it's a matter of collaborating probably better with our colleagues in division of diabetes control and other areas of chronic to to try to push that area of work towards implementing interventions So I wonder what you have found out about the risk of birth defects with the increasing proportion of births to older women. So we've done some analyses looking at maternal age and birth defects and it's actually a little bit of a U shape and it really depends on what birth defects you're looking at.
So like Dr. Feltgen pointed out, the risk for gastroesophageal disease is very low. is mainly among younger mothers, whereas the risk for some of the other defects is more among mothers who are over 35. And... So I think it depends.
It's definitely something that we keep an eye on and that we tend to adjust for a lot in our analyses because, as you know, the risk or the odds of a woman being obese is much higher as she's older as well. So those kinds of factors all come into play. I was thinking specifically about Down syndrome.
What's happened to Down syndrome in the last 20 years? Utah's perspective, I think it's been pretty stable. Certainly the risk goes up with maternal age, but we haven't seen any change that I'm aware of.
Our Twitter audience is getting very lively here. What can men do to prevent birth defects? I think couples should plan their pregnancies and make sure that if there are chronic diseases that they get handled before conception occurs. So there. And I think also from an occupational point of view, it is important that there are some occupational exposures that men perhaps could take home, so being aware of that is is important as well.
We have more. As a community health worker, I see lots of pre-pregnancy obesity. Should this be included as part of a reproductive life plan?
That's actually one of the things that in BD Steps we're looking at. We know that obesity is a risk factor. I actually have not seen any research yet, and if people want to correct me, where it shows that if you really lose the weight again before you get pregnant, whether that really helps.
I think it's a very solid recommendation to make, just because not being obese is healthier overall. But the true impact is something that I think we're still looking at. We're actually having a specific question in BD Steps.
asking a woman what her maximum weight was and when this was to see if she's actually lost weight, to see if that is still in any way, shape, or form associated with a birth defect. Okay. How are you addressing the prevalence of cytomegalovirus, the number one viral cause of birth defects?
I think in terms of CMV, if a baby is born and diagnosed with CMV embryopathy and they have a structural major malformation, they will be included in a registry. But often that's not the case, and what we may see is just a small head or microcephaly. And some states collect that information and some do not.
So unfortunately it's not always collected as part of the state surveillance system. Thank you So I'll let you talk too to see better but for the MbDPS and for BDSTEPPS we really have tried also to have study sites that kind of reflect the overall US population and And we do try to reach them by phone. So we're currently exploring, for instance, online questionnaires, knowing that that might limit some access.
So that's actually something that we want to look into to see whether that does indeed favor some access. some groups of people over others to estimate if that's something that we can do in the future. But for now, I think we really try to reach all women and give women an opportunity.
We're doing a pilot, for instance, in one of our sites in the next year, where if women don't have enough money to actually pick up the phone to do the phone interview, we're going to send out a cell phone to see if that would... aid in including because we really want to be inclusive and provide everybody with an opportunity to participate so that our data will also be as representative as possible. Last one. And part of this was answered in Dr. Mitchell's talk.
Have there been safety studies done on vaccination in pregnancy? Could you repeat the question? I'm sorry, I didn't.
Have there been? Safety, sure. Have there been safety studies done on vaccination in pregnancy?
If the question refers to influenza vaccine, there have been a number of safety studies, but one of the limitations in this session is focused on birth defects, is that most of the studies have considered birth defects as a single outcome and grouped them all together. And what we know from drugs that cause birth defects, effects is that they cause very specific birth defects and those may get lost if you will when you look at birth defects as a group. So what's missing from the many of the studies of safety of vaccines, influenza vaccines, is a focus on specific birth defects. The other factor which is just a reality is that every year pretty much the vaccine changes and even within a given year the manufacturing processes vary by company and so forth. So we really need to conduct studies every year of each year's vaccine.
And over the accumulated period of years, we develop a safety record, one hopes, which we so far have seen, that would be reassuring and would help reduce one of the major barriers to pregnant women receiving vaccination, whether it's pertussis or influenza vaccine. And that's concern about what harm it might do to their fetus. So we really need to assure the public that those studies are being conducted. I'd like to ask for another round of applause, real or virtual, for our speakers.
Thanks also to those participants who asked questions in person or virtually. Please join us next month where we will have an update on the Global Polio Eradication Initiative. Thank you very much.