Obesity and Neural Tube Defects: Don't Panic

by Kmom

Copyright 1996-2001 Kmom@Vireday.Com. All rights reserved.

DISCLAIMER: The information on this website is not intended and should not be construed as medical advice. Consult your health provider.




"I have heard about neural tube defects being more common in larger women. Should I worry?"

In 1996, two studies reported in the Journal of the American Medical Association found that large women had a higher risk of having babies with neural tube defects than women of average size.  The news media immediately picked up the stories and blared distorted versions across the nation, instilling fear in the hearts of large women everywhere that they could not possibly have healthy pregnancies or healthy babies.  This FAQ is an attempt to examine the issue more closely, both in what was reported, the concerns critics have had with the studies, and what the numbers really mean to large women considering pregnancy. 

The verdict of these studies are not a foregone conclusion; there are studies that contradict this information.  When looked at from a wide-ranging perspective, however, there are enough studies that have found a connection that suggests that some factor may be at work.  However, there is a complex interplay of factors at work here, and it is difficult to disentangle all the possible causes.  Is obesity really the problem, is it a metabolic problem that is common to larger women, is it undiscovered diabetes or a pre-diabetic state, is it nutritional differences, is it years of metabolic damage/chronic malnutrition from yo-yo dieting, is it socio-economic, or is it some other factor?  Research is really not clear right now on this point.  Something is going on, but what is going on is not clear at all.

However, the bottom line is that even IF the studies turned out to be confirmed by further research in the future, and even IF the problem is attributable only to fat and no other factor, a fat woman still has a greater than 99% chance of having a baby unaffected by neural tube defects

This is a fact conveniently ignored in the media reports and scare tactics of some doctors. Don't let the fear-mongering keep you from considering parenthood on that basis alone. The decision to have children is one that must be made carefully, with full consideration of all the health and emotional factors involved, but the implication that all fat women are doomed to have 'defective' children is not backed up by a closer look at the statistics.


What Was Reported

The Associated Press picked up the story of the 1996 studies and flashed it across the nation, where it was reported in various forms by local and national media. Only rarely was the full text used, and the 'hook' (emphasized point) was that heavy women were twice as likely (and extremely obese women four times as likely) to have a child with neural tube defects. Almost no media reported that even in its worst-case scenario, this would put the risk for heavy women still at less than 1%.

In the first study, they reported: 

Boston University researchers found that women who weighed 176 to 195 pounds before pregnancy were about twice as likely to have a child with a neural tube defect as women who weighed 110-130. The risk was four-fold for women weighing 242 pounds or more. The study involved 604 fetuses or infants with a neural tube defect born to women participating in birth defects research in Boston, Philadelphia and Ontario, Canada....

Also according to the AP press release, the second study: 

involved 538 babies or fetuses diagnosed with a neural tube defect from 1989 to 1991 in California...'Women with [a body mass] index higher than 29...had twice the risk of having a neural-tube-defect baby than other women,' said researchers led by Gary Shaw, an epidemiologist with the California Birth Defects Monitoring Program. 'Women who were obese -- whether they used vitamins or not -- still had a greater risk,' Shaw said.


The 1996 JAMA Studies

It is helpful to look more closely at the exact details of these two JAMA 1996 studies, as well as other studies that have examined whether there was an increased risk for NTDs with obesity.  Following are descriptions of the findings of the JAMA studies; further analysis follows in a later section.

Werler et al., Journal of the American Medical Association, 1996

Examined 604 fetuses or infants with NTDs and compared them with 1658 controls without other major malformations, and 93 controls without major malformations.  Women who weighed 80-89 kg (176-195 lbs.) had 1.9x the risk for NTDs, and women who weighed 110 kg (242 lbs.) or more had 4x the risk for NTDs. 

Although 4% of mothers with NTD-affected pregnancies reported having diabetes (onset before or during pregnancy), risk estimates did not change after excluding these women from analysis.  The authors did speculate that insulin's effects on metabolism might be behind the increased risk for NTDs, but dismissed this because the risk estimates did not change after excluding diabetic women.  This ignores that many women have strong insulin resistance long before they officially get diabetes.  Thus, perhaps insulin resistance or some other metabolic abnormality that precedes full-blown diabetes might be a factor.  However, this study did not examine that question.

The authors note that the connection with heavy women might be stronger in this study because it did not originally take into account fetuses with NTDs that had been aborted, and diagnosis of NTDs with ultrasound and AFP testing is more accurate in average-sized women.  In other words, some NTD diagnoses may have been missed in heavier women, while those that had been diagnosed in smaller women and thereafter terminated might not have gotten counted in the first few years of study.  Thus, the NTD-affected babies of leaner women might be under-represented in their data, and they theorized that might be why there was a stronger association in this study than in other similar studies.  

One of the most interesting aspects of the study was that when folate intake was considered, intakes of at least 400 mg of folic acid decreased the risk for NTDs by 40% in average-sized women, but did not reduce the risk at all among heavier women.  In the top several weight categories, there was about a 3x risk, regardless of folate intake.  The authors note that "the lack of protection from folate in heavier women must be confirmed in other studies,"  and they note that a similar effect was found in a clinical trial of zinc supplementation.  The authors also note that, "We cannot rule out confounding by other factors, particularly nutritional factors other than folate."  

The authors point out that the 'underlying mechanism' by which obesity might affect neural tube development is not clear, and they strongly state that "Nutrition, metabolism, and obesity must be studied further to better elucidate their roles in the development of the neural tube."  

Shaw et al., Journal of the American Medical Association, 1996

This study found that obese women (>29 BMI) had a 1.9x risk for NTDs as average-sized women. They extensively interviewed 538 women in California who had babies with NTDs, including those whose fetuses were stillborn or 'electively terminated'.  They compared this data with that of women who had 539 babies with no birth defects.  Women who were in the highest Body Mass Index category (>38 BMI) had the largest risk for NTDs, a risk of about 2.6x that of controls.  However, the authors note that the risk estimates for this group were imprecise statistically, so they should be viewed with caution. 

The risk for anencephaly was similar between average-sized and large-sized women, but the risk for spina bifida and other NTDs was 'substantially higher' in big women. Almost 50% of the women with birth defects were Hispanic, as compared to 36% of the controls.  Also, there was an increased NTD risk for short women, which has sometimes also been found in other studies.  

The authors explored several possible explanations for obese women having higher NTD risk, such as dietary folate intake, zinc intake, amount of dietary fat, use of a prenatal vitamin, dieting before pregnancy or in early pregnancy, alcohol use, etc.  None of these parameters were found to be statistically significant.  Nor were obese mothers with NTD-affected children more likely to have a history of high blood pressure, to use diet pills, or to not gain weight during pregnancy.  

The authors note that pregnancy after gastric bypass surgery has been noted to be associated at times with increased NTD risk, and observe that women were not asked whether they had ever had a gastric bypass.   Since gastric bypass is a fairly uncommon procedure (especially then), it is not likely that this is a significant source of increased occurrence of NTDs in the study, although it cannot be completely ruled out.  In a fairly small study, the presence of even a few gastric bypass pregnancies leading to NTDs might skew the numbers significantly.  But probably it is not likely that this was a significant factor.

Dieting can cause the body to spill excess ketones as it burns off fat; thus ketone production has been speculated to be related to NTD risk.  However, the study did not find that obese women on weight-reduction diets had higher NTD risk; they actually found a slightly decreased risk with it.  Of course, this is conveniently limited by the fact that they did not consider long-term dieting, only dieting in the 3 months prior to pregnancy or during early pregnancy.  It could simply mean that women mostly used 'healthier' diets that emphasized lots of fruits and veggies without significant caloric restriction.  Examining only the presence or absence of dieting in the prior 3 months (with no information at all on type of dieting) is hardly conclusive one way or the other, nor were the numbers strong enough for any real conclusions.  A much more in-depth and careful study would be needed for more conclusions on the issue of dieting and NTDs.

Since diabetics tend to have higher rates of NTDs, previous NTD studies have speculated whether undiscovered/undiagnosed diabetes is the reason for the higher rate of NTDs in obese women.  This seems logical.  The authors note this possibility, but observe that almost half of the obese women with NTDs would have to have been undiagnosed diabetics in order to see a twofold increased risk.  In addition, one would expect that if there were women with undiagnosed diabetes, that they would be diagnosed with gestational diabetes during the pregnancy at least, yet even when women with gd were excluded, the adjusted risks did not change.   Although it is possible that undiagnosed diabetes (or borderline glucose tolerance/insulin resistance) might have added to the NTD risk in obese women, in this study at least it is not likely that this is the total explanation.  

Study Concerns

These studies have been criticized on a number of issues. First, even the study's authors admit the need to duplicate the study and see if these results hold true. Martha Werler, lead author in the Boston University study, said that the finding "really needs to be confirmed before we can act on it." The media, unfortunately, jumped on the stories prematurely and hyped them irresponsibly without noting that other factors could be responsible for the findings, and that even if the findings are true, a large woman still has over a 99% chance of having a baby without neural tube defects.

Second, these studies were done after the fact by collecting observational data from reported cases of babies with neural tube defects in California, Boston, Philadelphia and Ontario. One study correlated weight with rates of NTDs, while the other correlated Body Mass index with it. Both found increased rates in 'obese' women. The authors did not include any explanation of this correlation but some of the authors did eventually speculate that it might be due to an abnormality in metabolism or nutritional factors.

The studies did not rule out possible related factors such as chronic dieting and its effects on metabolism, malnutrition or disturbed metabolism as a side effect of years of yo-yo dieting. Although the Werler study did look at dieting, it only examined it for 3 months before pregnancy, or during the first trimester of pregnancy, which is not exactly representative of chronic yo-yo dieting and its effects.  

The study noted that others had speculated that dieting might be a cause of NTDs, but found that dieting for 3 months before pregnancy was actually mildly protective.  It is important to treat that with caution and not overinterpret it, however----3 months is not a very long 'diet' and does not address what type of dieting was involved.  If a woman with chronic poor nutrition and sedentary habits went on a 'diet' that simply involved healthy eating and exercise, there could easily be benefit to that in preventing birth defects or other problems.  If a woman went on a extremely low-calorie diet before pregnancy (with significant ketosis), then that might actually present dangers.  It CANNOT be concluded from this small amount of information that dieting before pregnancy is beneficial in preventing NTDs, but it does present an interesting avenue for research pursuit, as long as researchers examine the results very carefully and do not lump all 'diets' together.  

The studies also did not look at the fitness and exercise levels of the women involved.  It would be interesting to compare the rates occurring in sedentary versus more active women, both large and average-sized, since this could also relate to the metabolism questions. These nutritional and metabolic factors are critical to consider and will hopefully be examined closely in future studies. Are the results directly related to obesity itself, or to conditions that could be (but may not always be) related?

Of definite interest is the issue of folic acid supplements not protecting against NTDs in larger women. Will this pattern continue to appear in future studies?  Is the standard recommended allowance of 400 micrograms (0.4 mg) an appropriate amount for a larger woman? Perhaps larger women need a higher dose because of a higher body weight? Or is the problem one in ability to utilize the folic acid? Does folic acid uptake/absorption differ in larger women? What could cause this difference, if there is one?

It is important that these questions all be answered before any conclusions are made about whether obesity CAUSES higher rates of birth defects. Other possible factors not addressed must be ruled out, and the relationship of proper nutrition and metabolic factors must be examined closely. 

The NTD rates of large women with excellent nutrition, stable weights, and regular exercise programs should be compared to the NTD rates attributed to overall populations and also to that of obese, sedentary, poorly-nourished women  and those who have dieted recently or chronically. It's possible that obesity may produce a situation which can cause defect rates to go up (such as malnutrition, too low a dosage of folic acid, or poor uptake of folic acid, etc.), but again it's too early to draw any real conclusions. All these studies do is indicate a need for further, more refined research.


Other Studies On This Subject

Although the two 1996 JAMA studies are the most famous on this subject, there are other studies that have examined the question.  What do these studies say?

Waller et al., 1994 - American Journal of Obstetrics and Gynecology

Article Title:  Are Obese Women At Higher Risk for Producing Malformed Offspring?

This study examined 499 mothers whose offspring had NTDs and compared them with 337 mothers of offspring with other major birth defects, and also with 534 mothers of offspring without birth defects.  Women who were "extremely obese" (BMI >31) had a 1.8x risk for NTD, especially spina bifida (a 2.6x risk).  Obese women also were found to have an increased risk for having an infant with other defects, including defects of the central nervous system, great vessel defects, ventral wall defects, and intestinal defects. The authors speculate about "potential mechanisms by which obesity could be linked to birth defects." 

One possibility they speculate about is vitamin-deficiency, either through poor nutrition or lack of taking a prenatal vitamin.  They observed that a recent survey by the National Center for Health Statistics found that only 27.6% of adults who were 'moderately or extremely obese' used vitamin and mineral supplements, compared with 38.8% of nonobese adults.  Similarly, the obese women in Waller's study were slightly less likely to be using tablets or cereals with the RDA of folic acid in early pregnancy.  They also tried to examine the question of whether obese women who used folic acid were still at higher risk of NTDs; there were too few of these women to answer the question.   

Other possible explanations the considered for higher birth defects in obese women included metabolic abnormalities.  They note, "There are many metabolic abnormalities associated with obesity, including high serum levels of insulin, triglycerides, uric acid, and endogenous estrogens and insulin resistance, chronic hypoxia, and hypercapnia.  However, as yet there are no studies of the risk of having offspring with birth defects among mothers with these types of abnormalities."  

At the end of the article, the authors rush to reassure heavy women.  They point out that in their study, women who are moderately obese BMI of 28-30, which is actually considered 'overweight' in most studies) do not have an increased risk of NTDs.  They also emphasize that "Pregnant women who are severely obese (body mass index > or = 31 kg/m2) should be counseled that although our data suggest that their risk of having an infant affected by a neural tube defect is elevated, their absolute risk remains low.  We calculate that the risk of a neural tube defect for an extremely obese woman living in California is 1.8 times the baseline rate, or approximately 1.8 per 1000 live birth and late fetal deaths."  

The authors also issue a strong and sensible caution at the end of their article.  They note, "There is at this time no evidence to support a recommendation that weight loss before pregnancy will reduce the risk of birth defects among offspring of obese women."  Unfortunately, this is not how most doctors and press members have interpreted the NTD studies or presented the information to big moms and the public at large.    

Watkins et al., 1996  - Epidemiology

Article Title: Is Maternal Obesity a Risk Factor for Anencephaly and Spina Bifida?

This study by the CDC studied 307 Atlanta-area women who bore babies with anencephaly or spina bifida, and compared them with 2,755 women who had babies with no birth defects.  After adjusting for age, education, smoking status, alcohol use, chronic illness, and vitamin use, they found that obese women (BMI>29) had 1.9x the risk for an infant affected by spina bifida or anencephaly.  

They also found that risk increased with body mass index; underweight women had a adjusted odds ratio of 0.6 for having an affected baby, versus 1.9x the risk for obese women.

Kallen K, 1998 - American Journal of Epidemiology  - from abstract

Article Title:  Maternal Smoking, Body Mass Index, and Neural Tube Defects

This study from  Sweden found that smoking was protective against NTDs, while women with a high BMI had a slightly higher risk for NTDs.  The risk for women with BMI >26 (just barely overweight) was 1.35, whereas the risk for women with BMI > or = 29 was 1.29.  Notes that there is no obvious explanation for BMI and NTDs, or the protective effect of smoking.

Feldman et al., 1999 - Fetal Diagnostic Therapy - from abstract

Article Title:  Distribution of Neural Tube Defects as a Function of Maternal Weight: No Apparent Correlation

This study did NOT find a correlation between obesity and NTDs.  From the Quest Diagnostic Lab database, 72,915 consecutive cases of biochemical screening that had documented weights and pregnancy outcomes were identified. Clients were divided into 5 different weight ranges and analyzed for occurrence of NTDs.  79 pregnancies had NTDs (incidence of 1.08 per 1000 pregnancies).  Differences between maternal weight ranges were not found to be statistically significant.  

They also divided the mothers into 'obese' and 'nonobese' 3 different ways, using 3 different cutoff points, and then analyzed these categories.  None of these were found to be statistically significant either.  They concluded, "Our present results do not support an association between maternal obesity and NTDs."  

The notable difference in this study is its methodology.  Other studies started by examining "x" number of cases of NTD-affected babies, and then randomly selected a number of controls to compare to the 'case' mothers.  Although randomization of controls should lower the chance for any possible coincidental problems, there is always a chance that even a random set of controls might coincidentally show an unexpected connection.  This study instead looked at a very large group of women who had all had diagnostic tests done, and then analyzed these by weight groups, eliminating the possible bias of randomly selected controls.  Perhaps that explains the different results.  However, since several studies of 'case' mothers and randomly selected controls all showed a possible connection between NTDs and weight, this does not seem a likely explanation.  

However, it is heartening that NOT all studies showed a connection between NTDs and the mother's size.  

Moore, et al., 2000 - Epidemiology

Article Title:  A Prospective Study of the Risk of Congenital Defects Associated with Maternal Obesity and Diabetes Mellitus. 

Data from 22,951 pregnant women enrolled in a prospective cohort study of early prenatal exposures and pregnancy outcome were studied.  It's important to note that this study looked for MANY types of major birth defects and not just NTDs; therefore, the risk factors and occurrence rates are going to be higher than those associated with studies that only looked at NTDs.  Keep that in mind when comparing study rates.  

This study found that in the absence of diabetes, obese women had no greater risk of having an offspring with a major defect. Obese mothers were no more likely to have a baby with NTDs, other neurological defects, urogenital defects, or cardiovascular defects. However, obese women had a slightly higher incidence of minor craniofacial and musculoskeletal defects in their offspring.

Surprisingly, women of average size with pre-existing diabetes had no higher risk for major defects.  Neither did women who developed gestational diabetes during pregnancy.  Both groups did have an increased risk for minor defects, nonetheless.  However, women who were BOTH obese and diabetic had 3.1x the risk for children with major defects, mostly craniofacial or musculoskeletal.  The authors suggest that "Obesity and diabetes mellitus may act synergistically in the pathogenesis of congenital anomalies."   

In this study, the risk for ALL major birth defects (NTDs plus all others) was 1.34% overall in non-diabetics.  The risk for major defects was 1.37% in women with BMI <25,  1.10% in women with BMI 25-27, and 1.47% in women with BMI 28 and higher.   The rate of birth defects was 5.88% in all women with diabetes; the rate was 1.38% in women with gestational diabetes.  When both obesity and diabetes were analyzed together, those women with both obesity and diabetes (pre-existing or gestational) had the highest risk of a major defect (4.13%).  

In terms of adjusted relative risk, obese women were no more likely to have a child with a major defect like NTDs, but were about 2.2x more likely to have a child with a minor craniofacial defect, and about 1.5x more likely to have a child with other minor musculoskeletal defects.  Women with pre-existing diabetes had 4.4x the risk for some type of major or minor anomaly, especially craniofacial or musculoskeletal defects.  Women with GD did not have an increased risk for major birth defects but did have a 2.6x risk of musculoskeletal defects in their offspring.   

With multiple logistic regression analysis, there was no increased risk of major defects in obese women with no diabetes, no increased risk among average-sized diabetics, but a 3.1x risk for major defects among women who were both obese and diabetic.  

This study speculated about what could possibly cause more birth defects in obese and/or diabetic women.  They noted several differences in their study population---this group was much more likely than those in other studies to have some college education, for example, which might affect things like dietary habits or use of vitamins---but they note that this would not affect the validity of comparisons within this study itself.   They speculated that women with GD and also obese women may have impaired glucose metabolism compared to others, and that this might have affected development.  They also noted that nutritional differences between groups might explain some of the problems.  

Notably in this study, obese women were more likely to lose weight in the 3 months before conception, and the authors observed that "Voluntary weight loss itself could lead to inadequate nutrient intake during a critical period of development for the fetus, even before a woman knew that she was pregnant."  Even with the significant weakness of considering only 3 months of dieting prior to conception, this factor might have accounted for some of the differences between groups in birth defects.  Unfortunately, they did not sub-analyze for dieting's effect in the obese group vs. the obese diabetics' group, which would have been the most informative.  So although we cannot say for sure from this data that dieting was a certain factor, it does not seem to have been protective here as it was in Shaw's study.  Again, looking at only 3 months of dieting is completely insufficient, the information here is not conclusive, and more careful investigation of this subject would be needed to know whether dieting is relevant.  


Possible Effect of Folic Acid

It is well-established medically that high doses of folic acid help dramatically lower the recurrence rate of NTDs in families that have already experienced a baby with an NTD.  Data also supports that a prophylactic dosage (0.4 mg) of folic acid probably helps lower the rate of NTDs in the general low-risk population as well.

One important question about the 1996 JAMA research was why folic acid supplementation seemed to have no effect on NTDs in big women, whereas it helped reduce NTDs in women of average size.  One possibility that some have raised is that perhaps big women need a higher dosage in order to be effective.  There is no data on this; at this time it is sheer speculation.  It might be instead that heavy women have a harder time utilizing the beneficial effects of folic acid, or that some metabolic problem interferes with efficient use of this vitamin----it really is unclear.

The Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada approved a statement in 1993 that recommended that women at increased risk for NTDs "should consider 1.0-4.0 mg folic acid supplementation after discontinuation of reliable birth control until 10-12 weeks after LMP."  Take note that this is a recommendation for an increased amount of folic acid (usual intake is 0.4 mg and they are recommending 1.0-4.0 mg).  They list those at increased risk for NTDs as being women with insulin-dependent diabetes, epilepsy treatment with valproic acid or carbamezapine, or those with a first degree relative with an NTD.  Note that they do not list obese women as being a group at risk, nor that they do not recommend increased intake in larger women.

However, there are some doctors and big moms who have decided to increase their folic acid intake somewhat, just in case.  Since very high amounts of folic acid (more than 1.0 mg) can sometimes make pernicious anemia difficult to diagnose, it is important not to just increase your dosage without consulting your doctor or midwife.  Some doctors and midwives are comfortable with women taking 0.8 mg of folic acid in pregnancy, while others may not be.  Occasionally, in women at higher risk, doctors have approved 1.2 mg or more with careful observation.  Consult your provider for advice on dosage on this important issue.  Also be sure to get plenty of foods containing folic acid naturally (spinach, asparagus, orange juice, lentils, etc.), as natural food sources are more optimal than supplements.  


Diabetes and NTDs

Women who are diabetic tend to be more prone to give birth to children with birth defects.  In particular, women who are obese AND diabetic seem to be especially prone to having children with birth defects.  As noted, Moore (2000) found that obese women who were diabetics had 3.1x the risk of having a child with major birth defects as women who were not obese and were not diabetic.  They theorized that perhaps the two of these factors working together creates the problem.

This might help explain the higher rate of birth defects in the JAMA studies.  Although women with known diabetes were excluded from the analysis, it's possible that at least some of the effect might have been from undiagnosed diabetes.  Moore further notes that Shaw's 1996 study included many fetuses who either died or were 'electively terminated' before gestational diabetes might have been detected, so therefore the role of possible diabetes-like pathology might be underestimated in the study.  

In Moore's study, they point out that they classified women who had GD in a prior pregnancy as having 'diabetes' for analysis, even if the fetus died or was terminated early, and that this would have helped detect the effect of underlying metabolic abnormality better.  Although diabetes of any kind was not that significant a factor in average-sized women, diabetes in women of size was a significant factor, and this classification may have helped it become so. 

There is much speculation that perhaps the higher rate of NTDs and other problems found among babies of obese mothers might be due to the metabolic problems associated with diabetes or a pre-diabetic pathology.  In other words, before a big mother developed outright diabetes, she might still have some metabolic derangements (including but not limited to poor glucose metabolism) that might affect a baby's development.  Insulin resistance syndrome (and its effects on various metabolic parameters) would be especially interesting to investigate.  


Other Possible Causes

Researchers have speculated any number of other possible causes.  Nutritional differences are a favorite theory, with zinc intake and methionine (an essential amino acid) intake receiving some attention.  However, there is no 'smoking gun' research among the various nutritional components that proves that nutrients other than folic acid are uniformly relevant.  Much more research needs to be done to understand how various nutrients influence the formation of the neural tube.

Other factors can decrease a woman's ability to utilize folate.  These can include smoking, alcohol use, birth control pill use, etc.  Some sources note that chronic dieting tends to result in B vitamin deficiencies, so it is important for studies to examine more than just dieting in the last 3 months before pregnancy.  

It's possible that ethnicity may play some role, especially as it relates to impaired glucose metabolism.  For example, Latinos in particular seem to have a much higher rate of NTDs than non-Hispanic whites.  Latinas and Native Americans are known to get gestational diabetes and diabetes at a much higher rate than whites of Northern European background, and there is a high rate of obesity among certain Latino and Native American populations.  Since Moore's study (2000) seems to show that the combination of obesity and diabetes tends to increase the rate of birth defects, perhaps obese women of the ethnic groups most prone to GD/diabetes are more susceptible to birth defects than those of other groups.  This seems to be borne out by Shaw (1996), where 50% of women with affected babies were Hispanic, vs. only 36% of the controls.  However, caution must be applied; ethnicity may not be the key factor here, and this issue has not really been studied very well.  More information is needed.

Another possibility that few have considered is hypothyroidism.  Many women of childbearing age have low thyroid function that goes undiagnosed and untreated.  Women of size in particular may have a problem with undiagnosed hypothyroidism; they often report difficulty in getting doctors to take these complaints seriously and test adequately for this problem.  Future studies should also examine the possible role of hypothyroidism or other metabolic concerns in the development of birth defects. 

Some authors have also speculated on the possible role of estrogens or other hormones in neural tube defects.  Heavy women are known to have higher levels of estrogens in general; perhaps this or other subtle hormonal differences could explain the higher rate of NTDs.  However, little research on this issue exists at this time.   

Many obese women have PolyCystic Ovarian Syndrome (PCOS), and this is known to create numerous metabolic disturbances, often eventually leading to diabetes.  It would be interesting to investigate this particular sub-group of obese women to see if they have an increased rate of birth defects compared to obese women without PCOS, especially since they seem to have more risk of complications overall compared to obese women without PCOS.  However, at this time, this remains speculation.   

In summary, no one really knows why obese women seem to have higher rates of NTDs in some studies.  Many possible causes have been proposed, but no one really knows for sure.  


What Does This Mean to Large Women Considering Pregnancy

First of all, it means not to panic. As noted before, large women still have tremendous odds in their favor. The risk of neural tubes defects in the general population is less than 0.2%; even if this risk is doubled or even quadrupled it still amounts to a risk of less than or equal to 0.8%  (and probably less). In other words, your odds of having a baby without a neural tube defect are still greater than 99%! These are pretty good odds! If you were given a lottery ticket and told you had a 992/1000 chance (worst-case scenario) to win 10 million dollars, would you feel pretty confident?  And other studies find the odds to be even better.  So don't spend a lot of time worrying about this issue.  Chances are it won't affect you.

Second of all, it may well mean that superb nutrition is even MORE important in pregnancy and beforehand for larger women. Malnutrition or uneven nutrition has been linked by some sources to the pregnancy complications most common to large women, pre-eclampsia and gestational diabetes (though of course these are multi-factorial). So perhaps this can also be related to a possible increase in neural tubes defects as well. In any case, there is an extremely strong case for PROPER NUTRITION before and during pregnancy, and a stable weight and regular exercise are probably also beneficial.  

Third, it may also mean that large women perhaps might consider a slightly higher folic acid supplement before and during pregnancy, but be sure to check with your doctor or midwife about dosage and any possible contraindications.  In studies reviewing folic acid intake and supplement usage, Kmom was appalled to see how few women actually get enough folic acid, either through dietary means or through vitamins/supplements.  GET SERIOUS ABOUT NUTRITION, and be sure to take a prenatal vitamin or folic acid supplement of some kind. 

Fourth, it may be even more important that fat women carefully check that their blood sugar is NORMAL BEFORE PREGNANCY.  This is vital!  Since some studies seem to show that the highest occurrence of birth defects seems to happen in women who are obese and diabetic, it is absolutely imperative that you check your blood sugar before trying to conceive if at all possible. If you are a woman of color or if you have PCOS, this is probably especially important.  If you have never been diabetic, check it to be sure that you are not diabetic before pregnancy.  If you have diabetes or have been borderline in the past, check it to be sure your blood sugar is EXCELLENT before pregnancy, and be sure to have a thorough check-up before pregnancy to address other concerns of pregnancy in diabetics. 

Fifth, it might mean that it is prudent to be sure that thyroid function is working normally before pregnancy.  Try to be tested before trying to conceive.  Hypothyroidism is simple to treat, treatment will not harm the baby, and may help prevent quite a number of problems if addressed appropriately.  Although hypothyroidism has not been examined in these obesity and NTD studies to date, it only makes sense to be sure this function is normal before pregnancy, regardless. Sometimes doctors are reluctant to check thyroid function in obese women so you may have to be insistent on getting this checked, or may even need to find a new provider if necessary.  But because hypothyroidism in pregnancy can cause numerous problems yet is so easy to treat, it is definitely something to be assertive about.  

What about weight loss?  There is no evidence that losing weight before pregnancy lowers the risk for NTDs.  Many doctors have used the 1996 JAMA research to suggest that obese women should lose weight before trying to conceive.  However, this research does NOT address that issue.  There is NO proof that losing weight before pregnancy would decrease the risk for NTDs.  And because of ketones or impaired nutritional status, it is possible that weight loss might actually increase the risk!  In fact, one of the studies directly commented on this issue, saying, "There is at this time no evidence to support a recommendation that weight loss before pregnancy will reduce the risk of birth defects among offspring of obese women."  The issue of weight loss and NTDs has yet to be definitively studied at this time.  Keep in mind that improved nutritional and exercise habits are ALWAYS a good idea before pregnancy, but that deliberate weight reduction through hypocaloric diets and strong food restriction might be harmful before pregnancy.  

Prenatal Testing may be a special issue for women of size.  Waller et al. (1994) strongly promoted the use of AFP testing in women of size, given the possible increase in risk for NTDs and other birth defects.  They noted that adiposity may make it harder to detect birth defects through ultrasound screenings, and that AFP screenings without compensating for increased weight may miss a number of cases of NTDs. Since the higher circulating blood volume of heavy women tends to dilute AFP levels, the dilution effect may cause lab technicians to miss some cases of high results (risk for NTDs), as well as resulting in more 'false-positive' low results (possible risk for Down's or Trisomy 18).  It should be noted that labs regularly adjust for weight now, which does improve accuracy somewhat.  However, some labs have reported overcompensating too much and creating excess numbers of high 'false-positives' on AFP tests (supposed risk for NTDs).   So AFP and associated test results should be interpreted with caution in big moms.

Is prenatal testing mandatory in women of size, especially given a possible increased risk for NTDs?  No, prenatal testing is never mandatory.  Given the higher rate of error in prenatal tests in big mothers, many choose not to utilize these tests.  Women who are especially concerned about NTDs and who would consider abortion should probably strongly pursue AFP and associated testing.  However, they should remember the decreased accuracy in big mothers.  Even when complicated formulas are used to compensate for the effect of weight, there is a higher rate of 'false-positives' on this test in women of size, so non-reassuring results should be treated with caution.  Women who would not consider abortion can also choose the test, but may want to re-evaluate its value in their case.   

Certainly, a fat woman does not have to select this test, simply because she is at a slightly increased risk for problems. Do not let a doctor pressure you into this test just for that reason.  Whether or not you choose prenatal testing options should be based on your beliefs about the value of testing, not about your size.  See the web section on Large Women and Prenatal Testing for more information on this issue. 



Although there is conflicting evidence about any possible connection between obesity and NTDs, there is enough data showing a possible connection for there to be real concern, and to show that more careful study is needed.  Although data that shows why there might be a link does not exist at this time, in Kmom's opinion it seems most likely that subtle metabolic problems that tend to cause a tendency towards obesity and glucose intolerance are probably also culpable for a somewhat increased tendency towards NTDs and minor birth defects.  However, this is simply 'best-guess' speculation at this point; no one knows anything for sure.

Remember that even if there does turn out to be a slightly higher risk for NTDs in women of size, the odds are still greatly in your favor, probably more than 99%.   This is the most important thing to focus on, and one that Waller et al. (1994) chose to emphasize----even if the risks are somewhat higher, the VAST majority of obese women will have healthy babies.  

It is completely normal to worry about even a small chance of problems, but really, the chances are quite small that you would be affected.  And remember that problems like these happen to average-size women too; it doesn't have to be a size issue.  There are a number of factors associated with birth defects; if your baby were to be affected, it could be because of another factor besides size.  If a woman is heavy, her size tends to get blamed for any problem that might be present, but while size might be a factor, it might also be completely unrelated.  Don't fall into the common trap of assuming that any problem has to be because of size.  It might be, it might not be, and it's very difficult to say for sure.

If you find that you are spending a great deal of time worrying about birth defects , you might want to explore those feelings on paper more thoroughly, because fears that are out of proportion to the risk involved often reflect an underlying issue that we need to deal with, like significant lack of body trust or fear of 'failure' or other such issues. This is often a great opportunity for healing and working on these issues.  It's normal to worry some about even small risks in pregnancy----as Pam England of Birthing From Within notes, "Worry is the work of pregnancy!"--but excessive worry indicates an issue that needs further exploration and healing.  If this is bothering you, take the opportunity to explore its meaning to you further.

Otherwise, concentrate on being as proactive as you can.  Get your blood sugar and thyroid function tested before pregnancy, if possible.  Practice excellent nutrition and exercise daily (after getting approval from your physician, of course). Take a daily prenatal vitamin, and consult your provider about the proper folic acid dosage for you.  Educate yourself about nutrition during pregnancy, and be sure to keep well-nourished, even when nausea makes it difficult. 

If you are not yet pregnant and you have dieted recently or are a chronic dieter, strongly consider taking time to stabilize your weight and maintain it for at least 6 months to a year. Concentrate particularly on replenishing the B vitamins in your body.  If you are already pregnant, do not continue to diet or try to consciously limit weight gain. Work hard instead on eating extremely well and exercising regularly and let nature take care of the proper weight gain for YOU. Proper nutrition is a strong first step in avoiding many pregnancy problems!  

Remember, chances are that everything will be fine.  


Research References

1996 JAMA Studies

Gary M. Shaw, Ellen M. Velie, Donna Schaffer: Risk of Neural Tube Defect-Affected Pregnancies Among Obese Women. Journal of the American Medical Association 1996, vol.275, pp. 1093--1096.

Martha M. Werler, Carol Louik, Samuel Shapiro, Allen A. Mitchell: Prepregnant Weight in Relation to Risk of Neural Tube Defects. Journal of the American Medical Association 1996, vol.275, pp. 1089--1092. 

Other Studies

Waller, DK et al.  Are Obese Women at Higher Risk for Producing Malformed Offspring?  American Journal of Obstetrics and Gynecology.  February 1994.  170(2):541-8.  

Moore, LL et al.  A Prospective Study of the Risk of Congenital Defects Associated with Maternal Obesity and Diabetes Mellitus.  Epidemiology.  November 2000.  11(6):689-94.  

Watkins, ML et al.  Is Maternal Obesity a Risk Factor for Anencephaly and Spina Bifida? Epidemiology.  September 1996.  7(5):507-12.  [abstract]

Kallen, K.  Maternal Smoking, Body Mass Index, and Neural Tube Defects.  American Journal of Epidemiology. June 15, 1998.  147(12):1103-11. [abstract]

Feldman, B et al.  Distribution of Neural Tube Defects as a Function of Maternal Weight: No Apparent Correlation.  Fetal Diagnostic Therapy.  May 1999.  14(3):185-189.  [abstract]

Suarez, L et al.  Neural Tube Defects Among Mexican Americans Living on the US-Mexico Border: Effects of Folic Acid and Dietary Folate.  American Journal of Epidemiology. December 1, 2000.  152(11):1017-23.  [abstract]

Shaw, GM et al.  Is Dietary Intake of Methionine Associated with a Reduction in Risk for Neural Tube Defect-Affected Pregnancies?  Teratology.  November 1997.  56(5):295-9. [abstract]

Shaw, GM et al.  Maternal Height and Prepregnancy Body Mass Index as Risk Factors for Selected Congenital Anomalies.  Paediatr Perinat Epidemiol.  July 2000.  14(3):234-9.  

Other Resources

ACOG Patient Education Bulletin.  Maternal Serum Screening for Birth Defects. American College of Obstetricians and Gynecologists.  August 1994.  Available from ACOG, 409 - 12th Street SW  Washington, D.C. 20024-2188.

Basic pamphlet written for patients considering prenatal testing.  Lists the risks for open neural tube defects as 1-2 in 1000 births.  This is similar to the risks listed in other publications, although of course it should be noted that risk can vary according to population and ethnicity.

Society of Obstetricians and Gynaecologists of Canada.  Statement of the Genetics Committee.  The Use of Folic Acid for the Prevention of Neural Tube Defects.  January 1993.  Available at www.gentlebirth.org/archives/folicacd.html


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