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Advanced Maternal Age: What’s All the Buzz About?

In the last issue of the American Journal of Obstetrics & Gynecology, a large Norwegian study was published by Camilla Haavaldsen MD, et al, which looked at the association of fetal death in relation to maternal age and length of gestation.  It is, after all, no secret that in many cultures around the world (not just the U.S.!) women are extending their childbearing years, considerably.  According to the March of Dimes, 1 in 5 American women have their first baby at age 35 or beyond.  Research then, which assesses pregnancy outcomes in terms of maternal age are important as this trend continues.

The statistics in the Haavaldsen study, not unlike others of similarity (referenced in the publication) are strikingly concerning.  The study’s conclusion states,

Women 40 years old or older had the highest risk of fetal death throughout pregnancy, particularly in term and post-term pregnancies.

For the tens of thousands of women who are delaying their childbearing years, the raw data and even relative risk numbers are staggering.

In many ways, this study seems to be well thought out:  potentially confounding variables were controlled for, including:  parity, plurality, year of delivery, paternal age and existence of pre-eclampsia (defined as maternal blood pressure > 140/90).  Following a complex system of data analysis, the blanket results were as follows:  of the 2,182,756 pregnancies studied between 1976-2006,  22,754 resulted in fetal deaths—1.049%.  Of note, the data came from the Medical Birth Registry of Norway—a compulsory method of tracking perinatal mortality rates which, of course, we here in the U.S. have no federally mandated system of any similarity.  Also of note, the results of over 28,000 pregnancies which lasted longer than 43 weeks were excluded due to coding problems—a reasonable enough number that could have had an influence on the overall results, had they been included.

The Details
The researchers aimed to relate maternal age ranges (five year increments between 20 and 45) to various weeks of gestation (16-22, 23-29, 30-36, ≥45) and, thus, determine “the association of fetal death with maternal age by length of gestation.”  In general, the results suggested that increased maternal age + increased weeks of gestation (>40yrs. old, >36 completed weeks of gestation) resulted in a significantly increased risk of stillbirth.   The resultant jump in risk of fetal death at term from >40-year-olds to >45-year-olds is almost two-fold.  Despite this, and other studies showing similar results, “Advanced Maternal Age” tends to include women aged 35 and above, rather than starting the definition at age 40.  (Recommendations on how to manage “higher risk” pregnancies in women >35 y.o. are also linked to well-documented increased risk of chromosomal birth defects as maternal age advances beyond 35.)

Admittedly, the data this large study provides is worthy of great attention.   However, before implementing practice guidelines based on these findings, such as “All women aged 40 or older should be disallowed to carry a pregnancy beyond 37 completed gestational weeks,” I believe several other factors need to be analyzed.

A Closer Look
We know that multiple underlying conditions, beyond those controlled for in the Haavaldsen study, are associated with increased rates of preterm birth and/or stillbirth, some of which include:  pre-pregnancy diabetes (and gestational diabetes), pre-existent thyroid disease, obesity and smoking.  Race, unfortunately, also plays a statistical role.  And yet, none of these potentially underlying factors are addressed in the study.  In fact, we have no idea how many of the study participants may have had one or more of these potentially confounding variables.  (This very issue is, interestingly enough, brought to light in the ACOG Guidelines for Stillbirth Management.)

Likewise, other factors that have not garnered much attention in the literature but, in my estimation, certainly influence a woman’s general state of health and well-being (and thus potentially, the health of her pregnancy) are factors such as: diet, exercise routine and overall stress level.   Designing a future study which could control for these additional variables would undoubtedly alter the data tremendously, prompting questions such as, “to what exponential degree does any one underlying condition increase the relative risk of fetal death?”  Likewise, assuming that the Norwegian study participants may have had some of the additional variables I suggest here, in some cases relative risk of stillbirth could even be decreased in any given maternal age group, when that/those underlying conditions were controlled for.   Following such a study, would it be feasible then, to develop an Adjusted Relative  Risk (ARR) Coding System for pregnant women which would go on to advise certain levels of perinatal and intrapartum care, based on the identified code?

Let’s take a look at a few hypothetical pregnant women to prove my point, but through a more intuitively analytical lens:

Sample Pt. Age Gest. Wks. BMI Smoker
Diabetes Thyroid Ds.

Woman A: 23 37.4 21 N N N
Woman B: 24 39.2 31 N Y N
Woman C: 36 38 24 Y N Y
Woman D: 41 41.5 20 N N N
Woman E: 44 42 23 N N N


What type of relative risk of stillbirth would these women likely have?

I think it is fair to say that, assuming all other potentially confounding variables are controlled for, Woman A has the lowest ARR and Woman E has the highest.  This is where statistics from studies like that of Haavaldsen, et al come in to play.  But what of the other women?

Woman B falls into the age range and gestational weeks that earns her an ARR of 1.00 (very low) in the Haavaldsen study, but how would that risk look differently  when we consider her BMI (indicative of obesity) and her positive gestational diabetes status?  She’d have a higher risk of stillbirth, right?

Woman C presents a similar quandary:  If, again, all other potentially confounding variables had been controlled for, her age and gestational weeks would place her in a relatively higher state of risk compared to Woman B (ARR would be 1.60 in the Haavaldsen study) but would this be an accurate estimation of her stillbirth risk?  What about her smoking and thyroid disease status?  Wouldn’t these earn her an even higher ARR, suggesting the need for an even greater degree of attentiveness by her health care provider?

Woman D presents a loftier challenge, still.  At 41-years-old and 41 weeks, 5 days pregnant, the Haavaldsen study would lead us to automatically believe she is at a relatively high risk for stillbirth as each day of her pregnancy progresses.  But what of her other health factors?  Does the absence of obesity, smoking and thyroid disease discount some of the risk her age and length of pregnancy create?

Anecdote
As a childbirth educator, I witnessed the angst provoked by our (currently limited) categorical risk assessment.  I recall one woman in particular—a 43-year-old first time pregnant woman who was rapidly approaching her due date.  Her healthcare provider—offering guidance from the most current research, I’m sure—was working hard to get her to agree to a labor induction.  Having prepared extensively for a normal birth, she was extremely frustrated by her doctor’s attempts to treat her as an at-risk mother of an at-risk baby.

“I feel fine,” she kept telling me.  “I feel healthier than I have in years.  Why do they want to induce me when nothing is wrong?”

This woman was an avid hiker and skier, she had a low-stress job, she ate healthfully, didn’t smoke, had no underlying medical conditions and appeared to have been of normal weight (prior to and during pregnancy).

I found myself, her Lamaze class instructor, stuck between a rock and a hard place.  I understood (I think) the impetus of her doctor—recognizing statistical trends, she wanted to save her patient from the potential heartache of a stillborn baby.  And, yet, this mother’s intuition kept telling her everything was fine with the baby, as well as with her own health status.

What really was the most appropriate approach to this woman’s care?

Other Factors to Consider
Other elements of the Haavaldsen study I feel compelled to mention include the suggested role labor inductions played in the cohort:

Term predicted by ultrasonographic examination may, for many obstetricians, be more trustworthy than term predicted by last menstrual period.  Hence, induction of labor may have been more common in pregnancies estimated to be postterm by ultrasonographic examination, than by [LMP].

Despite the mention of induced labors being included in the cohort, there are no numbers on how many of the 2 million + pregnancies ended in induction—leaving a potentially HUGE confounding variable unchecked.

Lastly, I appreciated the authors’ mention of the role cervical cone excision may have played in the early pregnancy stillbirth risk as well as preterm labor risk.   As the researchers described,

The relative risk of preterm delivery associated with cervical cone excision, increases with decreasing duration in pregnancy.  In preterm deliveries, fetal deaths are likely to happen during labor and are caused by immaturity.

Conclusion
The Haavaldsen study included a review of 37 similar works of research which, according to study authors, “demonstrated a significant increased risk of stillbirth in women of advanced maternal age.”  Because of that, (but despite the fact I, personally, hate the term “Advanced Maternal Age”) I don’t believe we can discount any and all motions to induce labor in women who fall into the highest of high risk categories.  But I also believe there is much more work to be done to further validate this data in terms of the multiple other risk factors associated with stillbirth.  Until we can complete this picture, in my mind, the jury is still out.

New Research, Practice Guidelines, Research, Science & Sensibility, Uncategorized , , , , , , , , , , , , , , , ,

  1. avatar
    Dawn
    January 6th, 2011 at 01:33 | #1

    “pre-eclampsia (defined as maternal blood pressure > 140/90)” I thought it was just hypertension and not pre-e. There are several factors for pre-e and that is the borderline high number for bp, or has the definition changed?

    Dawn

  2. January 6th, 2011 at 07:26 | #2

    ” in my estimation, certainly influence a woman’s general state of health and well-being (and thus potentially, the health of her pregnancy) ”

    In your estimation? Aren’t we supposedly talking about scientific evidence here? What do your unsubstantiated personal beliefs have to do with the validity of a scientific study?

    You cannot dismiss study findings that you don’t like simply because they don’t comport with your personal beliefs.

    “Despite the mention of induced labors … a potentially HUGE confounding variable”

    Kimmelin, inductions REDUCE fetal death. If inductions are a confounding variable, correcting for them would INCREASE the association between advanced maternal age and stillbirth, not decrease it, as you mistakenly believe.

    If you are going to dispute the results of a scientific paper, you need to offer scientific evidence to support your claims. Merely pretending the results aren’t true oif they don’t fall in line with your personal beliefs does not represent scientific analysis, merely the wishful thinking that is so characteristic of contemporary NCB advocacy.

  3. January 6th, 2011 at 09:44 | #3

    @ Dawn: Yes, I absolutely agree with you. The true definition of pre-eclampsia goes well beyond just a blood pressure of 140/90 or greater. This is, in fact, a point of frequent frustration for me–the post was just getting too long for me to take on yet another issue. The text of this study offers the “quick” definition of pre-e (as I wrote it in the post)rather than taking the space/time to define the entire thing. (Perhaps the researchers assumed their reading audience would make the leap on their own.)

    @ Amy: As is typical of your style of responding, you are taking a couple sentences out of context as fuel for your argument. I would encourage ALL readers to read through the ENTIRE post, at which point it will become clear that I am actually complemetary of the breadth and depth of this study, while at the same time calling for additional research to further inform practice guidelines.

    @ all: Please remember, the title and purpose of this blog is Science and Sensibility. To simply relay research results would be redundant (they are already availble through sources quoted and linked to). The purpose of this blog site is to bring scientific research to light and then offer a point of view on that research.

  4. January 6th, 2011 at 09:55 | #4

    “you are taking a couple sentences out of context”

    Really? In what way?

    “while at the same time calling for additional research to further inform practice guidelines.”

    Let’s be honest. You are suggesting reasons to discard the findings of the study. Didn’t you write:

    “in my estimation, certainly influence a woman’s general state of health and well-being (and thus potentially, the health of her pregnancy) are factors such as: diet, exercise routine and overall stress level. Designing a future study which could control for these additional variables would undoubtedly alter the data tremendously”

    That is not a call for more research. If that’s not an attempt to imply that diet, exercise and stress level will alter the findings, what is it?

    And what about claiming that inductions are “HUGE” confounding variable without mentioning that correcting for induction would only increase the strength of the data, not decrease it?

  5. avatar
    sara
    January 6th, 2011 at 12:08 | #5

    Umm…it doesn’t take a rocket scientist to reasonably conclude that diet, exercise, and overall stress level can have a profound effect on pregnancy. Actually, research supports that a healthy lifestyle including a healthy diet, regular exercise, and a lower level of stress hormones is very beneficial for pregnant mothers and babies. (not to mention the general population!) Why shouldn’t a study relating to AMA also include those variables?

    Even an ex-doctor such as yourself, Amy, should be interested in those findings.

  6. January 6th, 2011 at 15:46 | #6

    I had the pleasure of hearing many researchers from Norway present at the Marce Conference. I was struck by the country’s birth registry as a profound way of contemplating data, and gaining some good longitudnal evidence. Great to get more info on current research from this area.

    I also find the language of women’s health so fascinating. Terms like AMA (advanced maternal age) are so easy to use, and granted we need some agreed upon vocabulary with which to communicate–but from a transpersonal perspective, as your anecdote offered, a woman’s experience of her “age” transcends measurement. I continue to love that no matter how hard we try, we can’t define the nature of anything a woman’s body does, or doesn’t.

    And I am so intrigued in the comments by how difficult we seem to find other women speaking about what we think is ours. No one owns anything. Thank God.

  7. January 6th, 2011 at 18:34 | #7

    I found this to be a very interesting study, but I actually came away with more questions.

    My first question is, What about those 28,000 women? That’s an awfully large number to just throw out. I am not sure which way they would shift the data, but with that large of a number, I am sure that the outcomes and conclusions might very well have been different-more definitive one way or the other.

    I do think that Haavaldsen should have clearly stated how they defined pre-eclampsia. If they were truly using acceptable criteria, there must have been some way to succinctly state this. Without doing so, we are left to question if they were really assessing pre-eclampsia or gestational hypertension. Given the scope, I am inclined to believe that they did in fact use accepted criteria for pre-eclampsia but, like many areas of this report, did not clearly define their methods and we are to make the assumption.

    I would also like to know how many of the women had confounding issues such as diabetes or thyroid disease. Was this a racially homogeneous study group? How will this data translate to a study population that is more African American, Asian and/or Latina? In my experience, African American and Latina mamas are more prone to preterm labor so recording their specific outcomes may not have a huge bearing on the study’s current outcome. However, it would be nice to know, especially for making recommendations to a diverse population like the US.

    As far as potential lifestyle habits, I am not sure they are as strong confounders for post date deliveries as they are for preterm deliveries. These researchers have been pretty thorough so I am inclined to believe that they may have controlled for these variables when matching study participants.

    Finally, I would like to have the numbers on how many women were induced. This is an important number because if inductions occurred in more still births or if more women without inductions had still births, that definitely influences the recommendation.

    The one problem that I find with this paper is that some things are not clearly spelled out. I think that if they had clearly stated demographic data of the study participants, then much of the discussion we have in the comments to this post would not exist, we’d have the answers within the reported study.

    Overall, I think that this study does well to answer the question of whether or not older moms should be allowed to carry to term or even post dates. Older moms should definitely be monitored more closely as they approach their due dates and if they advance beyond, induction certainly has to be considered. The only flaw that I see is in how the researchers described their study participants (not listing demographic data and lifestyle habits), not recording and including the 28,000 women who were markedly post dates (who could potentially alter the conclusions significantly) and not listing who was induced and who was not and their birth outcome.

    I suspect that Haavaldsen has this information and if it could somehow be added to the paper or submitted as an addendum, then for me, the issues would be settled. As it stands, I don’t really feel we need more studies on this topic, but clarification (a simple matter of editing) of the information already presented.

  8. avatar
    comadrona
    January 9th, 2011 at 04:02 | #8

    I saw a new mum today (44) who was a victim of the faulty thinking resulting from this study. She was frightened into an elctive C/s at 38 weeks, having been told that it was dangerous for her to carry the baby past 37. She is shocked at how painful the aftermath is and how badly breastfeeding is going as a result. But her baby was conceived naturally – it is well known that IVF is a significant, if poorly understood, factor in stillbirth. Why was this important issue not addressed? Also, perinatal mortality is still roughly at the same rate (1%) as it has been for 50 years, though the reasons are different. I don’t argue with the need to monitor “older” mothers perhaps a bit more closely, particularly the IVF ones, but it is also important for them to feel that they have a fightng chance at normal birth when all is well. Let us not forget that induction of primips had more than 50% likelihood of ending in C/S and this surgery is still more risky for mother and baby than vaginal birth. P.S. This mother was also given steroids prior to the birth – huh?????????? the baby was not premature!

  9. avatar
    Eric Christopherson
    May 15th, 2011 at 10:50 | #9

    I’m amazed that you haven’t mentioned the analysis done in the Norway study that focused on data from 1987-2006. For it is very different in its findings in comparison to data dating back to the 1960′s. For example, the stillbirth risks for the babies of over 40 moms are about double the younger moms, rather than five times worse. Obviously there have been significant improvements in care over the time of this study.

  10. avatar
    Mary
    August 26th, 2011 at 03:26 | #10

    Thank you Kimmelin
    I am 43 yo 40weeks 1 day and was automatically booked into an induction -mainly due to the recent information such as this study.
    I want the safest and best delivery for my baby and believe this to be vaginal natural birth(from my research) so I was disappointed to face induction when my body / baby is not ready (VE confirms this) but of course we want minimum risk (as does every mother!) so I researched again to find out what are the risks of induction? and of the individual methods? (eg stillbirth was stated risk for oxytocin augmentation) and C sections? etc. I felt there were risks on both sides that gave me need to stop and consider more deeply.
    After finding and reading your article I felt stronger about questioning the OB – it is balanced, thoughtful and helpful article – and about enquiring further. Since then the midwives agreed that induction automatically seemed unnecessary for a healthy mother, no other indications, healthy baby and so have arranged to monitor me daily up to 40 plus 7. We will reassess daily.
    Thank you for the article.

  11. August 26th, 2011 at 06:43 | #11

    Mary,
    I applaud your diligence in seeking information that is right for you. Please do keep us posted on how things go.

  12. February 3rd, 2012 at 08:06 | #12

    This is a very interesting topic and I think the discussion will only increase as more women choose to delay parenting to concentrate on careers. As women rightfully gain more equal rights in the workplace, although this is a slow process, childbirth will be delayed. It’s positive to see that studies are being undertaken, so we can analyse the risks involved and avoid heartbreaking situations like miscarriage. However, we should take into account the circumstances of each study and analyse the merits of their findings. Some researchers may have predetermined ideas that they wish to portray through their data and that is something we should be wary of.

  13. avatar
    Sophie
    August 30th, 2012 at 21:27 | #13

    Thanks Kimmelin for this article as it voices so much of my concerns and questions. I have been feeling pressured to have excessive monitoring and be induced, the sooner the better it seems. I’m 40 and it’s my first baby, but I’m 100% healthy, fitter than most women half my age, with no medical conditions. I find that I’m pigeon holed due to my age, but going on age alone just doesn’t stand up. What are the other factors in the figures that show the higher rates of still birth after 40? What about the mother’s health and lifestyle? – as these are surely contributing factors? I want a home water birth but the midwife is still deciding on whether to agree. I’ve felt so powerless throughout this pregnancy to get the birth I want and so much angst and upset. We the Mother’s are what matters, please can the medical world listen to the people they are trying to help!

  14. avatar
    Julia
    September 13th, 2012 at 03:45 | #14

    I also want to thank you (and other posters). I am 40yo, pregnant with first baby. I’m under a lot of pressure to induce at 40+0 weeks because of AMA. I’m currently at 36 weeks and trying to make informed decisions. I need to weigh up risks of induction (leading to other interventions and emergence ceasarean more likely) against going a few days over EDD. My OB claims it’s a ‘no-brainer’, but it is not for me – clearly a higher relative risk of still birth, but still a very low absolute risk.

  15. September 13th, 2012 at 08:06 | #15

    Julia,

    Good for you, for taking the time to look into this carefully. You are right to look at relative risk vs. absolute risk. Also, paying attention to what your body (and baby!) are telling you is always a good thing. What do your instincts tell you? There is not a single, blanket policy on this that works for every woman–issues like this MUST be approached on a case-by-case basis. Statistics are helpful in pointing the way–but they do not offer complete answers to questions like this.

    I know women who have suffered the devastation of losing a baby for no apparent reason in their third trimester, who have gone on to question whether an induction at 38 weeks (or 37 or 39…) would have saved their child. I also know women who have gone against their provider’s advice to induce early (because of “advanced maternal age”) and have delivered beautifully healthy babies. I’ve known women who have consented to labor inductions and have had horrific outcomes that have taken YEARS to recover from…as well as the women who have agreed to an induction and experienced zero identifiable negative outcomes. In fact, I have four specific women in mind–one for each scenario outlined above.

    I’m sure you have also heard plenty of stories by now (perhaps many of them unsolicited!), representing all sides of this debate. Most of us working in this field can cite specific cases to support our personal perspectives on this issue–whichever perspectives we may hold.

    But at the end of the day, YOU have to feel comfortable with whichever decision you make…and listening to your body, your baby, and your instincts can be just as helpful in making that decision as listening to your provider. ALL of those sources of information must be taken into account and carefully weighed.

    All the best to you in these coming weeks.

  1. January 6th, 2011 at 00:46 | #1