Prenatal Weight Gain: The Importance Of Study Design

We've been discussing prenatal weight gain politics for "obese" women again.  This is part of a continuing series we're doing on nutrition and weight gain in women of size during pregnancy.

To recap briefly -- how much weight fat women should gain during pregnancy is a very hot topic in obstetrics these days. A number of studies on restricted gain have come out in the last several years, and there are certain to be many more in the future. In addition, the Institute of Medicine released newly revised guidelines for weight gain earlier this year, changing the recommended gain for "obese" women from "at least 15 lbs." to "11-20 lbs." (a slightly lower recommendation than before, but not as low as critics wanted).

The hope among those who promote restricted gain is that the risks of pregnancy in "obese" women might be reduced or eliminated by restricting weight gain, and that this might also prevent obesity from getting worse in the long run for the mother, and perhaps prevent or lessen it for the child.

Earlier in our series, I wrote about a Kaiser study started last year (and publicized in the New York Times) about promoting ZERO weight gain in pregnancy for fat women.  Then we discussed the research showing harms already associated with little gain in pregnancy in "obese" women, and what harms might result if the weight gain recommendations are reduced even further. 

Today we talk about study design limitations in weight gain restriction research, and how the design of most studies does not allow them to conclude that restricting gain is "safe." 
Let's take a critical look at the research on this topic.

The Kaiser Study

Just in case you missed earlier posts on it, I'll repeat some of the details about the study from the Kaiser press release on October 21, 2009.

Kaiser Permanente is launching the first clinical trial to help obese women control their weight during pregnancy...“The goal of the {"Healthy Moms"] study is to keep obese pregnant women from gaining weight. We believe they can safely maintain their pre-pregnancy weight and deliver healthier babies,” says Kim Vesco, MD, MPH, a practicing OB/GYN and researcher at the Kaiser Permanente Center for Health Research, who will direct the study.

This is the first study to test a weight maintenance program for obese pregnant women, and the first to use weekly support groups as part of the intervention. A small study in Denmark did limit excess weight gain in obese pregnant women, but they still gained an average of 14.5 pounds. Two other larger studies failed to prevent excessive weight gain in obese and overweight pregnant women.

“It may seem counterintuitive to suggest that women control their weight during pregnancy, but these women are already carrying between 50 and 100 extra pounds — and for them any more weight gain could be very dangerous,” said Vic Stevens, PhD, principal investigator who has studied weight loss and weight maintenance for more than 30 years...

The “Healthy Moms” trial will enroll 180 obese pregnant women from Washington and Oregon who are members of the Kaiser Permanente health plan: half will receive one-time dietary and exercise advice; the other half will attend two individual counseling sessions and then weekly group counseling for the remainder of their pregnancy. Women who attend the sessions will be weighed and encouraged to keep and turn in daily food and exercise diaries. Professional weight counselors will facilitate the groups and help motivate the women with behavior change techniques.

The study will follow women throughout their pregnancies to find out how much weight they gain, how large their babies are, and how much weight they retain one year after they give birth. It will also look at birthing complications, the baby’s growth and feeding practices, and whether the mother continues with dietary changes after the baby is born. The study will recruit women for 18 months, and preliminary results are expected in three years.

Remember, the researchers publicized this study before they had even done the research.  This is not objective research; this is Science By Press Release, designed to push a pre-set agenda.

The title of the NY Times article was "New Goal for the Obese: Zero Gain in Pregnancy." Although the article briefly discusses the controversy over whether gaining no weight is safe, many people will come away from the article with the conclusion that no weight gain is the standard of care and the best goal for "obese" women during pregnancy.  This is pure public relations marketing in order to push a public health agenda that has actually not yet been proven to be safe or effective.

This is only the first in a plethora of studies to come on little or no weight gain in pregnancy, as bariatrics obstetrics specialists push their agenda of strictly enforced weight gain in fat women.  But can studies like this one really conclusively decide the safety and effectiveness of such an approach?

Concerns About the Study Design

I have a number of concerns about the study design of this study (and of all of these "limited gain" studies).  Let me summarize the main ones.

Sample Size Issues

One major concern is whether the studies will be large enough to detect the influence of low gain on relatively rare outcomes like stillbirth.

Most of these studies on restricting weight gain either do not report on low gain's effect on stillbirth, or the studies are so small that they are not powerful enough to detect a difference in such rare events as stillbirth. 

However, some large studies not specifically on restricting weight gain have found an association between low weight gain and stillbirth even in "overweight" and "obese" women, but rarely are these mentioned in the studies promoting restricted gain. 

This Kaiser study will have 180 women in it. Only half (90) will be in the arm that intervenes to prevent weight gain. Can a study group of less than 100 accurately show that stillbirth rates (usually a few per thousand) are not affected by restricting weight gain?

Yet I have no doubt that the researchers will conclude at the end that restricting weight gain is "perfectly safe" and has no untoward negative effects. The problem is, they will not have investigated that at all.  Their study does not even begin to have the power to determine whether such an approach is "safe."

And frankly, a study arm of less than 100 is not enough to determine much of anything for certain, let alone to push a policy change with potentially far-reaching consequences.

Causation Versus Correlation

Another problem seen constantly in these weight gain prevention studies is confusing causation with correlation.  This is particularly prevalent when trying to tie together weight gain and pre-eclampsia. 

A number of studies (like the Missouri study and the Cedergren study mentioned above) have found that obese women with lower weight gains have lower rates of pre-eclampsia. Therefore, they imply that if we can prevent fat women from gaining much weight, we can lower their risk for pre-eclampsia (PE).

The problem is that fluid retention is one of the symptoms of pre-eclampsia; it does not mean that restricting weight gain prevents pre-eclampsia. 

Just because there is an association between two things does not mean there is a causal relationship.  Because increased weight gain is a side-effect of developing pre-eclampsia, it is hard to distinguish whether or not a higher relative gain causes PE or is merely a by-product.

In other words, women with lower gains have less pre-eclampsia, but that doesn't mean that deliberately restricting weight gain will prevent pre-eclampsia.

These studies should note that there is an association between low weight gain and less pre-eclampsia, but not necessarily a causal connection. Yet many of these weight gain studies strongly imply that if we keep fat women from gaining weight, fewer of them will develop pre-eclampsia.  It is simply not possible to make such a conclusion at this point.

The IOM pointed out this problem in their report on weight gain recommendations.  So did Nohr 2008:

Any causal interpretation of the association between total weight gain and these complications is limited.  For pre-eclampsia, high total gain most likely reflects pathologic fluid retention as part of the disease.

I bet this issue gets no more than a passing mention (if that) in the Kaiser study when it's published.

Controlling for Iatrogenic Influences

Another major problem with these sorts of studies is whether they control for iatrogenic influences.

In other words, if doctors know how much weight women gain in pregnancy, this may strongly influence the outcomes.

For example, doctors are often of the firm belief that too much weight gain leads to too-big babies (marcosomia) and big babies "need" cesareans to prevent shoulder dystocia (the shoulders getting stuck and causing birth injuries).

Yet research clearly shows that when a doctor believes a baby to be macrosomic, the cesarean rate in that group skyrockets, even when the baby is not actually big.

Sometimes this is because doctors use higher rates of induction of labor when babies are believed to be big, and a number of studies show that induction of labor strongly increases the cesarean rate in macrosomic babies. However, sometimes it's also simply because the doctor is quicker to intervene and declare "failure to progress" or "cephalo-pelvic disproportion" when they believe the baby is macrosomic.

In other words, the doctor merely believing that the baby is going to be big influences the induction rate (increasing the risk for a cesarean), and influences how the doctor manages labor and decides to go to a cesarean.

And doctors believe that fat women have big babies when they gain "too much weight" in pregnancy.

So if doctors are not blinded to weight gains, it's quite likely that the low-gain "obese" women will have fewer cesareans and the high-gain "obese" women will have more......but it won't prove that more gain causes more cesareans. 

Instead it just creates a two-tier system where the "good" moms who gain within recommended parameters get more chances of avoiding a cesarean, and the "bad" moms who gain "too much" are penalized, consciously or unconsciously. 

Not blinding the doctors to weight gain to rule out iatrogenic influences is a serious design flaw of nearly all of these restricted weight gain studies. 

Too-Short Follow-Up for Mothers

Another concern is the lack of long-term follow-up for the mothers. 

One of the major goals of the study is to see if preventing weight gain reduces the mother's obesity long-term. 

Designing a study to have a short follow-up makes it easier for the study to look successful, which is why most weight loss studies have limited follow-up periods.  It makes them look more effective than they really are.

For example, the follow-up period of one year in this study is not nearly long enough to show a significant influence on the mother's weight. A follow-up of at least five years is necessary to make any conclusions about long-term improvements to health or permanence of weight loss.  This study doesn't have nearly enough length. Any study with such a short follow-up is trying to make their results look more favorable.

Sure, the less weight you retain after pregnancy, the better, so the one-year result is not irrelevant. But neither is it conclusive. Weight loss research clearly shows that most weight loss begins to disappear after a year to two years, and most will usually be regained if the study subject if followed long enough.

If followed long-term, often the subjects in weight loss studies end up heavier or with more belly fat than they began.  Will the subjects with no gain in this study have less total weight in five years, or will they merely experience a bigger rebound effect? 

This is an extremely important question...but it's one that's not being asked.

To follow up these mothers for only one year is not long enough to make real conclusions about their health or weight trends.

Lack of Long-Term Follow-Up for Babies

Most of these intervention studies look at very short-term outcomes, examine the babies for only extremely abnormal outcomes (like birth defects) right after birth, and proclaim the intervention "safe" if the baby is not harmed in any obvious way. But that doesn't mean the intervention really was safe, because harm is often more subtle than that.

A longer follow-up is vitally important to really determine the safety of restrictive gain protocols. 

In the New York Times article, this concern was briefly noted, pointing out that many fat women who lose weight during pregnancy produce large amounts of ketones, which may impair a baby's cognitive development.  Long-term follow-up is needed to determine whether cognitive development is impaired in babies whose mothers' weight gain is restricted, but no such follow-up is planned in the Kaiser study.  As the NYT article notes:

There are concerns. The major one is that women who are not gaining weight will burn fat for energy, producing acidic compounds called ketones, which could be harmful to the fetus. Studies in diabetic women and in animals have found that babies born to women who had more ketones in their blood had lower I.Q. scores than other babies, said Dr. Naomi E. Stotland, an assistant professor of obstetrics, gynecology and reproductive sciences at the University of California, San Francisco...

The Healthy Moms study will follow the women throughout their pregnancies to find out how much weight they gain, how big their babies are and how much weight they retain a year after the birth, looking at complications, the baby’s growth and feeding practices and whether the mother continues with a healthier lifestyle after the birth. Skeptics say they need to track additional measures, like the babies’ long-term cognitive development.

This is an extremely important point.  Possible cognitive effects from high levels of ketones is one of the major concerns that has not been addressed in any of these weight-gain restriction studies, and almost never is it even mentioned in the studies.  You cannot possibly conclude that major restriction should be the new norm without examining this question. 

Furthermore, we know from famine studies that babies who are exposed to famine conditions while in utero experience long-term health complications, including a tendency towards more diabetes, more high blood pressure, more heart disease, and more obesity.

In particular, babies who experience undernutrition in the womb but then are born into environments with plenty of nutrition have the highest risk for later problems.

I'm sure the women in this Kaiser will not be put on starvation diets like women in true famine conditions, but no one knows the long-term effects of milder rates of undernutrition. 

Messing with fetal nutrition is tricky stuff.  Human metabolism is incredibly adaptable, and babies often survive seemingly "fine" under horrendous conditions. Yet when you look at them long-term, this survival and adaptation often comes at a price. 

You simply cannot look at a baby immediately after it is born, note that it has not been born with any obvious birth defects, and then conclude that your highly restrictive program in pregnancy is beneficial or even perfectly safe. 

To determine real safety, there has to be long-term follow-up of babies in this type of program...but none of these programs have any.

How Do They Plan To Restrict Weight Gain?

Whenever one talks about restricting weight gain in obese women, the question becomes how do they plan to restrict gain, and what will they do to enforce it?

The Kaiser study doesn't really elaborate on specifics other than "two individual counseling sessions and then weekly group counseling," including weekly weighings and daily food and exercise diaries. Nor do they mention what will happen with "obese" women who gain weight anyhow.

If the plan is simply to discourage junk food and increase exercise, all well and good---but this would be good for all women, regardless of size.  Why just target fat women for this? People of all sizes eat "junk food" --- some in really significant amounts --- and it's not any better for the baby of a skinny woman than it is for the baby of a fat woman. And reasonable exercise is good for virtually everyone in pregnancy.  Why not emphasize healthy habits to all pregnant women?

(Answer: Because they have the typical assumption that all fat people eat terribly and need to be educated about their poor choices.)

If the program is just about emphasizing reasonable habits and targeting junk, great. Good nutrition and exercise in pregnancy is important. But if the plan goes beyond that and resorts to also limiting caloric intake, the question of relative fetal undernutrition comes into play, which raises a lot more questions about safety.

If they plan to strictly limit carb or caloric intake, do they plan to have participants test daily for ketones? If they are limiting calories and/or carbs, they should be checking ketones daily....but no mention of such monitoring is made in the press release.  Nor will they have long-term follow-up of babies subjected to these protocols.

The press release does not say how they will achieve "zero weight gain" in women of size, but it's hard to believe there will not be some degree of caloric restriction involved if they expect women to not even gain the weight of the baby, placenta and fluids.  How will they determine how many calories are enough, how will they monitor for problems, and how draconian will they get?

And what counselors will recommend if a "morbidly obese" woman actually gains weight in her pregnancy despite their program, as many probably will.....will she be told to restrict calories or carbs even more? Told to exercise in extreme amounts? Told to drink Slim-Fast? Will she be hassled about the gain?  Will she penalized with early induction or planned cesarean because she gained weight?  What happens to women who exceed the acceptable gain?  There's a lot of potential for problems here.

It's also important to point out that the question is not just what this particular study will be promoting, but also how OTHER doctors will interpret the "gain no weight" paradigm and what methods they will use to enforce this goal.

Fat women already report many harmful dieting practices being recommended to them in pregnancy in order to limit weight gain. Some women are merely told to eat less in pregnancy than when non-pregnant.  Some are told to drink Slim-Fast in pregnancy to limit weight gain. Others are told to limit their caloric intakes to 1800, 1500, or even 1200 or 1000 calories.  

And that was in the days when fat women were being encouraged to gain at least 15 pounds.

What kind of draconian recommendations will be made to "obese" women if they are supposed to gain no weight in pregnancy? Or to lose 10, 20, or even 50 pounds during pregnancy?  (Yes, those are all real recommendations told to women of size just recently.)

The question in studies like these is how restrictive is too restrictive, what follow-up is being done to see whether there is long-term harm with even mildly restrictive practices, and how other medical practitioners will go about incorporating and enforcing "no gain" mandates. 

This must not be glossed over, but is an important part of any study or public health policy that consideres seriously limiting pregnancy weight gain. Some doctors may limit weight gain in fairly reasonable ways, but other practices may resort to draconian interventions with a much higher potential for harm.

Is the Research Really Objective?

Finally, the fact that the researchers in this study are in bed with the weight loss industry is troubling; their results are going to be colored by that fact.

The Kaiser study employs a weight loss "expert" as a consultant; look at the language the "expert" uses in the press release: "For [the obese women], any more weight gain could be very dangerous."

"Any more weight gain could be very dangerous?" Does that sound like an objective observer to you? One open to any finding, even if it means finding the hypothesis invalid? Or does it sound like one who has already made his own conclusions, before the study is even done?

Just as we shouldn't trust the tobacco industry to come out with reliable findings on the safety of cigarettes, or should have a jaundiced eye when examining pharmaceutical research sponsored by drug companies, we shouldn't trust someone in the weight loss industry (which profits from consultations like this) to objectively conduct research on topics like weight gain restriction.

Many of these weight gain studies are rife with personnel who are on the staff of, consult with, or have a vested economic interest in weight loss companies and services.  And remember, consulting on weight gain restriction studies is a potentially vast new market for weight-loss companies and they know it.  They are hardly impartial bystanders in such research.

This is a tremendous conflict of interest but one that is rarely ever noted or questioned.

My Psychic Predictions

Putting on my all-seeing magic turban, I psychically predict that at the end of the Kaiser study, the women who gained less weight will have lower cesarean rates and less weight retention at the end of one year. Gosh, quelle surprise!

But is that really a function of the lower weight gain, or a function of the beliefs and practice patterns of their doctors? And of the small follow-up period?

It's one thing to propose a hypothesis and then do a study to collect data to see whether or not your hypothesis was correct. That's the scientific method.

However, that's not what these researchers are doing. They publicized the study before any results were even in because they are sure they know what results are going to be reached. 

Doing a study with a foregone conclusion is not good science. Furthermore, the study has to be of a size and design to accurately test your hypothesis; the Kaiser study is not. 

An objective study would look at all the possible benefits and risks from restricting weight gain, would be large enough and long enough to detect the real risk of harm associated with restricting weight gain, and would have no sponsors or associates who might benefit economically from a restriction program.

Yet very few of these restriction studies look at all possible harms, have large-enough sample sizes to detect harm reliably, and have long-term follow-up to detect more subtle harms. And many of them involve, directly or indirectly, researchers or consultants who are part of the weight loss industry.

The fact that they publicized the study heavily ahead of time in a major national publication, before the data was even collected or analyzed, strongly suggests that what they are really trying to do is push an agenda that NO weight gain is best for fat women, regardless of what the data actually say.

Conclusion

Again we are back to prenatal weight gain politics.

The bariatric obstetrics establishment is dismayed that the Institute of Medicine did not cave into their pressuring tactics and did not drastically lower their weight gain guidelines for obese women last year. They see it as a rebuke to the research and press releases they've published thus far.

So they are now pushing back with an aggressive marketing campaign designed to get out the message that fat women should gain very little in pregnancy. Except it's not enough anymore that fat women be kept to far lower weight gains than other women. 

No, now the research is taking a disturbingly extremist tone and pushing for NO gain and even weight LOSS, despite the fact that research shows some significant areas for concern (higher rates of prematurity, small-for-gestational-age babies, and possibly stillbirth) with very low gains, and despite that fact that restricted gain studies have major design flaws.

Now, to be fair, many who specialize in bariatric obstetrics probably truly feel that they are "saving" fat women and babies everywhere by promoting such draconian limits. They feel that the IOM is dragging its feet and endangering babies in the meantime.

And it's important to note that there is some research that really large weight gains (35 to 44 lbs. or more) may be harmful on average in "morbidly obese" women, resulting in higher rates of big babies, perineal trauma, postpartum weight retention, and perhaps perinatal mortality. So there is a case to be made that very high weight gains are not a good idea for women of size in general.

But without adequate (and far more thorough) study, it's impossible to establish the safety of very low weight gain limits.  And given previous and recent research, there is good reason to suspect that promoting weight loss or limiting weight gain too much could well produce more premature and/or small-for-gestational-age babies...or worse.

Even if these researchers don't make the IOM revise its guidelines any time soon, they know that aggressive marketing will start building an expectation in the public and in OB-GYNs that strictly limiting weight gain in fat women is "standard of care." 

We are already seeing this happen.  I'm hearing from more and more fat women that are being told that they are not allowed to gain ANY weight in pregnancy, or even that they must lose weight during pregnancy.

Increase attention to the importance of healthy eating and regular exercise in pregnancy?  I'm ALL for it, as anyone who knows my website and my past writings can attest.  I believe in Health At Every Size, and I believe that people should be gently encouraged to examine how they can improve their lifestyle and health, and never more so than in pregnancy.

Except I believe that such a program should be marketed to all women, regardless of weight/BMI, not just the fat ones.  Poor habits are not found only in "obese" women; care providers just assume that they are most egregious in this group.  But such attention to healthy habits would benefit many women and babies, and an emphasis on habits would be far more beneficial than a rigid emphasis on weight gain.

And creating rigid gain guidelines that may be unsafe and that have unrealistic expectations (zero weight gain or weight loss for all women of size) and which penalize anyone who falls outside those expectations (gained 21 lbs. in pregnancy?  It's planned cesarean for you!) is a terrible bastardization of what "healthy eating in pregnancy" programs should really be about. 

Remember that this study and press release is really about marketing limited weight gain to the public and to doctors, and that no conclusion about the safety of limiting gain in women of size has really been proven yet.

Far more research (and far better research) needs to be done to determine optimal prenatal weight gain in women of size. This Kaiser study is not it.

For now, I agree with the Cochrane Database, which concluded:

Protein/energy restriction of pregnant women who are overweight or exhibit high weight gain is unlikely to be beneficial and may be harmful to the infant.

Instead, the better approach may simply be to concentrate on excellent nutrition instead of prenatal weight gain. Barbara Luke, MPH and RD, summarized this in 1998 when she said:

Perhaps the obstetric goal should be to ensure optimal nutritional status during pregnancy, focusing on the quality and quantity of the preconception and prenatal diet rather than the crude and imperfect measure of gestational weight gain.

Commonsense words indeed.