Don't Count Your Eggs Before You Know the Research

Brainchild: Does Mommyhood Make You Smarter?

2008-10-30T15:14:00.000-07:00

I have no clever scientific critique of this hypothesis, as it seems to be based entirely on animal studies. But after experiencing a notable loss of mental function after giving birth, this article made me a little hopeful:

How Becoming A Mother Can Boost Your Brainpower

Good Times

2008-10-13T23:03:00.000-07:00

I just found another reason to love the New York Times -- the "Really?" series examines popular medical claims, many of which are related to reproductive health. For example:

A woman is more fertile after a miscarriage

Morning sickness means a girl is more likely

Menstrual cycles can synchronize over time

Twins always skip a generation

Regular use of hot tubs can hurt fertility in men

You Make the Call: Using Cell Phones During Pregnancy

2008-10-05T23:03:00.000-07:00

Did you see this headline earlier this year? Warning: Using a Mobile Phone While Pregnant Can Seriously Damage Your Baby!

I didn't catch this headline when it appeared back in May, but when I finally saw it this week I was alarmed enough to investigate further. Interestingly, it seems that the popular news media may have actually corrected itself on this one: a follow-up article from ABC News actually attempted to de-sensationalize (my word) the news. They actually sought the opinion of the author as well as a couple of real, live, well-respected epidemiologists to properly interpret the results of a study that linked mothers' cell phone use with behavioral problems in their children. In their words:

"We think it is interesting, but many associations seen in studies of this type occur due to chance."

"I think this is a competently and well-done study, but I think there are enough red flags that this should probably not be something the U.S. public needs to be alarmed about."

"This study is well worth publishing [in a medical journal]. But, given its highly preliminary and unexpected nature, and its liability to any number of methodologic problems, it is not the kind of study that should be making news in the general public."

I thought this last comment was particularly relevant to this blog -- all too often, I read a sensational headline in women's health that has snatched a preliminary finding from a mediocre study and turned it into an immediate! alarming! truth!

This is not to say that mediocre studies are useless. All epidemiologic studies are susceptible to problems; that is the nature of studying human beings who cannot be manipulated and controlled under laboratory conditions. It often takes a number of epidemiologic studies, each flawed in its own way, before a real association can be established. The purpose of this blog is to discuss and understand some of the most common methodologic problems, so that we can interpret the headlines through a more discerning lens.

In the meantime, don't throw your cell phone away.

A Few Good Reads

2008-09-30T15:58:00.000-07:00

First of all, check the comments section of my last post to find the answer to your pop quiz. I hope you passed :)

The New York Times health section has a few good general interest articles this week:

1) Searching for Clarity: A Primer on Medical Studies. Author Gina Kolata explores the significance of clinical trials, sample sizes, and supporting evidence. I have a hunch that all the epidemiologists out there conducting observational studies might feel a little miffed by the conclusion of the article.

2) Applying Science to Alternative Medicine. Author William Broad discusses the lack of scientific evidence to back up the "extravagant" claims of some alternative medicine proponents, and highlights the National Center for Complementary and Alternative Medicine, a division of the National Institutes of Health that is seeking to apply rigorous research methods to evaluate these claims.

Pop Quiz

2008-09-25T20:41:00.001-07:00

An intriguing headline this week: "Antidepressants May Harm Male Fertility". Check out this brief article from New Scientist magazine and tell me if you can spot any problems with this study.

Because We're All Friends

2008-09-23T12:57:00.000-07:00

I forgot to mention in my post yesterday that epidemiology is often referred to fondly by its nickname, "epi" (EH-pee). You know, we're very casual people. So since it is kind of hard to type out the full words all the time, and 2 syllables are better than 7, from here on out you will probably see me write about Epi and Repro Epi...just so you know.

You Study...Skin?

2008-09-22T11:05:00.000-07:00

Often preceded by a confused expression, this is the reaction that I generally get when I tell people that I am an epidemiologist. I don't think it helps matters when I try to explain that an epidemiologist could theoretically study skin, in fact an epidemiologist can study whatever he/she wants, but that I don't actually study skin...

According to a couple of esteemed epidemiologists, "epidemiologic research involves describing and interpreting patterns of disease occurrence in populations, in order to generate knowledge that can be used to prevent disease and avoid human suffering" (-Weiss and Koepsell, Epidemiologic Methods)

Basically, we study large populations of people, measure exposures and outcomes, and use this data to try to find out what factors might influence a person's risk of disease. A classic example of this is the discovery that smoking causes lung cancer; although it seems obvious now, there was a time when this connection was not accepted. It took a number of epidemiologic and laboratory studies to convince the world that smokers should probably stop smoking.

And although we might use epidemiology to study diseases of the skin, an epidemiologist is actually not anything like a dermatologist. Hope that makes sense.

Another Post in the "Amazing" Category

2008-09-20T23:55:00.000-07:00

You may have seen this in the news a few months ago - human ovulation captured on film for the first time. Please check it out.

BPA Update: The New Study on the Block

2008-09-20T23:52:00.000-07:00

BPA is back in the news, big time. The first major study of BPA in humans was published in the Journal of the American Medical Association on Tuesday (and the original study is available online for free for your reading pleasure!). Until now, almost all of the BPA research has been conducted in animals; although they are very useful, animal models of disease do not always translate directly to humans. In fact the European Food Safety Authority affirmed the safety of BPA based on fundamental shortcomings of the animal models, such as the fact that humans metabolize and clear BPA from the body much faster than rodents (see my previous post summarizing the positions of various regulatory agencies).

So this is a great opportunity to review our first study together in detail, step by step, and it is a wonderful study design to begin with. I hope that this post will leave you with a better understanding of the latest development in the BPA saga. Please leave a comment to let me know if this was helpful; constructive criticism is welcome.

CITATION

Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, Melzer D. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA 2008; 300(11):1303-1310. Published online September 16, 2008. (doi:10.1001/jama.300.11.1303).

STUDY DESIGN

Cross-Sectional (please pause here for a moment and read my previous post on cross-sectional studies).

STUDY POPULATION

The National Health and Nutrition Examination Survey (NHANES) is a nationwide study that recruits a representative sample of 5000 Americans to complete interviews and undergo physical examinations. Remember that because NHANES is a cross-sectional study with no follow-up, it can only provide useful information about prevalence. Actually, NHANES provides an excellent glimpse of the health status of Americans; for example, we might use NHANES data to determine the percentage of Americans with cancer or STDs, or the amount of sugar-sweetened beverages consumed by kids in the U.S. These statistics are frequently cited and often used to guide national health policy. One very practical product: the pediatric growth charts used to plot childrens' height and weight gains were derived from NHANES data.

This particular study was limited to 1455 NHANES participants who were between 18-74 years old and had provided a urine sample that was analyzed for various environmental toxins.

EXPOSURE OF INTEREST

Bisphenol A, or BPA, was measured in a "spot" urine sample. This means that the sample was provided at one particular point in time, as opposed the collection of all urine voided during a 24-hour period, or several urine samples collected over the course of years. The advantage of the spot urine sample is convenience. The disadvantage is that the content of urine is highly variable, depending on the time of day and recent exposures. In this case, the spot urine sample provides information about only the most recent BPA exposure, and does not necessarily tell us anything about long-term exposure to the chemical. In other words, a very high or very low BPA level measured in a spot urine sample may just be a fluke. Someone who actually has very little cumulative exposure to BPA may have just coincidentally decided to microwave his breakfast in a plastic container for the first time right before the NHANES exam, and so his measured urinary BPA level is falsely high and not an accurate reflection of his lifetime exposure to the chemical. In epidemiology terms, we call this measurement error.

OUTCOME(S) OF INTEREST

NHANES participants were asked: "Has a doctor or other health professional ever told you that you have (angina/arthritis/asthma/cancer/chronic bronchitis/coronary heart disease/diabetes/emphysema/heart attack/liver disease/stroke/thyroid disease)?. This type of disease measurement is called "self-reported"; the classification is based entirely on what the study participant says he/she has. Let's talk about measurement error again - there are a number of reasons why self-reported disease status is likely to be inaccurate. One subject may actually have diabetes and not know it yet. Another subject may remember her doctor saying something about her thyroid, and jumped to the conclusion that she has some sort of thyroid disease when she actually doesn't. Ideally, the self-reported diseases would be verified (epi term: validated) in some way - by checking against medical records, or lab tests, or on-site physical examinations - but this would obviously be very expensive and time-consuming in a study with thousands of subjects.

RESULTS & DISCUSSION

In future article reviews we will look at the results in more detail, but for now I think it is sufficient to boil it all down to one statement (the one that's received all the publicity this week). The take-home message: higher urinary BPA levels are statistically associated with cardiovascular disease and diabetes.

So the reason we examined the study design, population, and exposure/outcome measurements in detail was to create a context for evaluating this statement. This. Is. Essential. This is the point of my blog. I sincerely hope you are still reading at this point, because my entire goal is to help you look beyond the headlines, beyond the talking points and the sensationalized blurbs that too often misrepresent the actual research.

There are a few key things to remember when you think about the results of this study:

- This is a cross-sectional study, so we cannot know for sure whether the BPA levels preceded the disease, or if there might be some biological reason that people with cardiovascular disease or diabetes are exposed to or excrete more BPA (epidemiology term: reverse causation).

- The spot urine samples are not necessarily a good measure of long-term exposure to low doses of BPA, and this low lifetime exposure is what scientists are most concerned about.

- There is a lot of speculation about the potential negative effects of BPA on human reproduction; this study did not attempt to investigate any reproductive outcomes.

- This is ONE study. We can't conclude that BPA causes heart disease or diabetes from this study. It should absolutely be considered in the body of evidence concerning the health effects of BPA, but we should not freak out over one study like this. Replication, replication, replication! We need more studies to confirm these findings.

My take-home message? My hunch is that BPA probably isn't kosher; I'm limiting my exposure and especially my son's exposure (without going overboard) until we know more. Let's get serious about it and encourage some more extensive studies. I'll do my best to let you know as the research emerges, especially as it relates to reproductive outcomes.

Cross-Sectional Study Design

2008-09-18T22:58:00.001-07:00

The cross-sectional study is one of the simplest of the epidemiologic designs: the basic idea is that the risk factor or exposure of interest and the outcome of interest are measured at the same point in time. There is no follow-up in a cross-sectional study. They may also be called "prevalence studies", because they measure the proportion of individuals with a particular outcome at a specific moment in time (the prevalence of that outcome).

Imagine recruiting a group of subjects for our ground-breaking study on hair color and depression (we wish to determine whether blonds really do have more fun ). We randomly select 20 women to come to our office, where we will record information about their hair color (blond versus non-blond) and their apparent depression level (smiling versus frowning). In a cross-sectional study design, these pieces of information are recorded at the same time. It would be like gathering our study population together and taking a single photograph of them to record their status at a particular moment in time:In this snapshot, 5/10 of the women with dark hair color are depressed (frowning) and 2/10 of the women with blond hair color are depressed. Therefore the prevalence of depression among non-blonds is 50%, and the prevalence of depression among blonds is 20%.

Aside from the potentially offensive study hypothesis and the absurdly simplified measure of depression, what other problem comes to mind? The main limitation of the cross-sectional study design is the inability to determine whether the risk factor of interest preceded, and therefore could have caused, the outcome of interest.

In our snapshot, we observed that non-blond hair color was associated with a higher prevalence of depression. But in order for non-blond hair color to be a risk factor for depression, we would have to establish that the hair color preceded the depression. Since we measured hair color and depression at the same time, we do not know which came first, and there are 2 possible explanations for the association we observed:

1) Women are born with dark hair color, which predisposes them to develop depressive symptoms (blonds have more fun)

2) Women with depression are more inclined to dye their hair a dark color (or conversely, happy women tend to dye their hair blond -- fun women have more blond!)

Now, you may decide that one of these explanations is more believable (plausible) than the other, but the point is that we cannot establish with certainty direction of the association:

Cross-sectional studies are a quick and relatively inexpensive study design that can provide valuable information about prevalence and possible exposure-disease associations. However, it is important to keep in mind the limitation discussed here when you are interpreting the results of a cross-sectional study.

Dirty Diapers, Sleepless Nights...x 5

2008-09-15T00:15:00.000-07:00

This case report from the journal Fertility and Sterility describes a woman in Pakistan who recently delivered quintuplets successfully.

It gets better...they were conceived naturally. Spontaneous conception of quintuplets has been estimated to occur in only 1 in 65,610,000 pregnancies (that's a 0.0000015% chance!).

But wait! It still gets better...this woman had not received proper prenatal care before showing up to the hospital around 35 weeks of gestation. Ultrasound revealed multiple fetuses, but the doctors could not tell if there were four or five babies.

Can you believe it? There's more...ultrasound also showed that all fetal presentations were breech.

Have you had enough yet? Because, you guessed it...this woman refused cesarean delivery and delivered ALL FIVE BREECH BABIES VAGINALLY.

The largest baby weighed about 5.5 lbs, the smallest about 3.5 lbs. The mother and all her children were doing well at the time this article was submitted for publication, 5 weeks after delivery, and the authors included an appeal for contributions to cover the cost of the woman's care. They also included a very sweet picture of the kidlets (sorry, copyrights apply).

Amazing.

Bisphenol-A: What's the Deal?

2008-09-12T22:46:00.000-07:00

If you're anything like me, you are pretty confused about the on-again-off-again controversy over bisphenol-A, the compound that may leach from some plastic containers and may cause damage to fetal and infant development. I gave up trying to figure out what the deal was a long time ago and bought the BPA-free bottles for my son so I could sleep at night.

But now I am a responsible scientist-blogger! No more avoiding the issue. I thought I'd put together a few notes to help you, and me, understand where the experts stand at the moment:

Key:
Green = don't worry about BPA...at least not yet
Yellow = the jury is out; you may or may not want to worry about BPA
Red = you should definitely worry about BPA

Food and Drug Administration (as of 8/15/08): still evaluating the risks of BPA as new information arises, but currently not recommending any changes to food contact materials that contain BPA because average adult/infant exposures appear to be well below the acceptable limit; a meeting of the experts will be convening this month to discuss the ongoing assessment
Chapel Hill Bisphenol-A Expert Panel (as of 7/27/07): very concerned about the potential adverse health effects of exposure to low levels of BPA, especially in fetuses
National Toxicology Program (National Institute of Environmental Health) (as of 9/3/08): there are reasons for concern, but the level of concern ranges from "some" to "minimal" to "negligible"
Health Canada (as of 4/18/08): found that exposure levels in children and adults are well below levels causing health effects, but banned polycarbonate baby bottles anyway
European Food Safety Authority (as of 7/23/08): average exposure to BPA is well below the tolerable limit and the human body quickly metabolizes and eliminates ingested BPA, so no concern to anyone

Looks like we haven't reached an agreement yet, folks. Stay tuned for more information, including an answer to the question: "Why is BPA so bad?"

Speaking of Headlines...

2008-09-08T10:32:00.000-07:00

My primary purpose in starting this blog is to teach women of reproductive age how to read the latest news in reproductive research with a healthy skepticism. I've collected quite a few recent publications that I want to review in detail, but before diving into the real research I want to highlight a headline that popped up in my RSS feeds this week:

"Acupuncture May Hold Promise For Women With Hormone Disorder".

Orac at Respectful Insolence has already thoroughly slammed this press release, so I won't spend too much more time ranting. While I do not share Orac's extreme distaste for acupuncture (at least not yet), I am similarly dismayed by the publication and dissemination of a headline like this to promote a study that has not been published, peer-reviewed, or even completed!

From the perspective of the lay reader, specifically women struggling with PCOS and infertility, this headline offers unfounded hope. There are a couple of red flags that must be highlighted here:

First of all, this study is on-going. The press release gives no information how close to completion it may be, only that the study has been going on for about a year and the investigator needs more participants. Publicizing "results" like this before the study is complete and the analysis has been independently evaluated defeats the entire purpose of the peer review system.
More importantly, the "results" are one-sided. We read in the press release that several study participants have achieved pregnancy, and one subject in particular attributes her third pregnancy to the acupuncture treatments. This must spark the first fundamental question: Is there a control group in this study? If we cannot compare the women who received acupuncture to women who did not receive acupuncture, then we can not conclude that these pregnancies were in any way associated with the acupuncture.

Thankfully, our friend Orac has already done the hard work of investigating the study design, and reports that there is indeed a control group in this study who receive "sham acupuncture" (like an acupuncture placebo). Great, one point for study design! Now the next question that must follow, given that there is a control group: How does the success rate in the acupuncture group compare to the success rate in the control group? And this is where we are left with no useful information, in fact, we are given misleading information. The press release alludes to several subjects who achieved regular menstrual cycles and pregnancies during the study, but we have no idea if these successes occurred in the subjects who actually received acupuncture! What if all the pregnancies occurred in the placebo group - then we might actually conclude that acupuncture is detrimental to your fertility!?!

Perhaps when this study is completed, reviewed, and published, we will find that the acupuncture treatments really are associated with positive reproductive outcomes, and that acupuncture does indeed hold promise for women with PCOS. But this little blurb may be the only "results" from this study that are ever released to the public, and it leaves the average reader with an unduly positive impression of acupuncture in the treatment of hormonal disorders.

And We're Off!

2008-09-04T22:14:00.000-07:00

You like the blog title? Yeah, it's cheesy. And I'm okay with that.

My intention in starting this blog is to practice science writing while keeping up with the research that most interests me, and might interest you too, if you happen to be a woman my age. I'll be reviewing recent headlines in reproductive epidemiology, the type that your mom may have already clipped out of the health section of her newspaper and mailed to you.

I've been a student of epidemiology (more on that later) for over 5 years now, and if there's one thing I've been thoroughly trained to do, it is criticize the literature. It turns out that the little newspaper blurbs your mom has been sending you don't always get the research right. So here I am, trying to set the record straight by going back to the source, reading and reviewing the original research articles and helping you understand what the science really says.

Let's put this doctoral training to some use!