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Jul
2

Keeping a study in perspective: C sections, stillbirth & ectopic pregnancy

written by Tara Haelle

You may have caught a headline some time yesterday telling you that having a C section will increase your risk of having a stillbirth or an ectopic pregnancy in a future pregnancy. Before you freak out (if you have or may need a C section) or tout the findings while lamenting high C section rates*, there’s a lot more you need to know about that study. A LOT more.

Fortunately, the study doesn’t seem to be getting a lot of press so far, which is good. It’s an example of one of those studies written for other researchers, not for the lay public (even though it’s open access, so you can read the whole thing yourself without paywall). The findings in it may have some significance for future research, but they don’t have much clinical significance, which is to say they don’t affect how prenatal care, fertility care and birth planning are practiced.

No, you don't need to worry about stillbirth or ectopic pregnancies after a C section. Photo by Roberta Lott.

No, you don’t need to worry about stillbirth or ectopic pregnancies after a C section. Photo by Roberta Lott.

First, let’s discuss what the actual study found and how some news media may be unfortunately likely to report it. In plain context-less terms, the study found that having a C section for a first birth increases the risk of stillbirth by 14% in a future pregnancy and increases risk of a future ectopic pregnancy by 9%, compared to having a spontaneous (non-induced) vaginal delivery for a first birth. The findings were based on analysis of 832,996 women who had a first-time live birth between 1982 and 2010 in Denmark and were followed until they had another baby, they died or left the country, the study ended or they had a miscarriage, stillbirth or ectopic pregnancy.

Broken down by type, the increased risk of stillbirth was 15% for emergency C sections; for elective C sections, it would have been an 11% increased risk, but this finding did not reach statistical significance, which is to say they couldn’t rule out the possibility that the increased risk was just chance. The increased risk of later ectopic pregnancies was 9% for first-time emergency C sections and 12% for elective ones. Interestingly, the risk of a miscarriage in a later pregnancy after having a C section in a first birth was 28% *lower*, compared to first-time vaginal births. That seemingly contradictory finding (C sections increase stillbirth risk but decrease miscarriage risk?) ought to give you pause, but we’ll get to that in a moment.

Already, these numbers are VERY small, but they’re also relative risk, which isn’t terribly helpful if you don’t know the absolute risk of having a stillbirth or ectopic pregnancy. The actual risk is incredibly small.  The rate in this study, with 1,996 stillbirths across all the women, was 2.4 stillbirths per 1,000 women. Then, only 0.03% more women having C sections had a stillbirth than women having vaginal births, based on these results.

Or, put another way, it would require 3,333 women to have C sections before even ONE of them has a stillbirth that would not have occurred among 3,333 women having vaginal births. Yet another way to look at it: If 10,000 women have a baby vaginally and none have a stillbirth later, then, according to the findings of this study, among 10,000 other women who have a C section, three would have a stillbirth later.

Tiny numbers.

The findings were similar for ectopic pregnancies. With that outcome, 0.1% more women having C sections experienced a later ecoptic pregnancy than women having vaginal births did. Ectopic pregnancies (the egg is fertilized by sperm in the fallopian tube and implants there instead of in the uterine lining) are estimated to occur in 20 out of every 1,000 pregnancies, a rate of 2%. So if 2% of women who had a first-time vaginal delivery have an ectopic pregnancy, then this study means 2.1% of women who had a first-time C section would have a future ectopic pregnancy. It would require 1,000 women having C sections before one additional one had an ectopic pregnancy.

If I’m being repetitive with how I present these numbers, it’s because I want to drive home how tiny this association is, especially before I tell you the next part about this study: they didn’t consider all the possible underlying conditions that could have led to the C sections in the first place. In fact, the authors even say themselves, “This increased rate of stillbirth could be due to underlying factors contributing to the need for a cesarean section, and not the cesarean section per se.”

What did they control for? The final risk calculations were found after adjusting for the mother’s age, origin, marital status, socioeconomic status (education and income), history of stillbirth/miscarriage/ectopic pregnancy, year of giving birth, and history of medical complications in the first live birth (having multiples, diabetes, gestational diabetes, placental abruption, placenta prevue and hypertensive disorders such as pre-eclampsia). They also adjusted for the first baby’s birth weight and the week of pregnancy when born (gestational age).

What did they NOT adjust for? The mother’s weight (body mass index), for one. Keep in mind that being overweight or obese is a risk factor both for pregnancy complications and for C sections, so not taking this into account is pretty significant. They also didn’t have complete data on whether the mothers smoked or underwent fertility treatments, or on the causes of stillbirths (for all but 15 years of the study) or reasons for C section requests (for all but 8 years of the study).

In addition, they did not have complete information on whether the stillbirths occurred before birth or at/during birth. They separated the stillbirths into explained (675) and unexplained (186), information which was only available between 1982 and 1996 (hence the reason the numbers don’t add up to the total stillbirths). Even this information is not terribly helpful to health care providers. The authors wrote, “Almost 50% of the explained stillbirths in this cohort were due to antenatal complications (including placental abruption/infarction, intrauterine growth restriction, preeclampsia, prematurity, and poor placental growth). The clinical importance is that although many of these complications are largely not preventable, an increased awareness that the fetus is at risk may facilitate increased surveillance and optimally timed delivery and may lead to improved perinatal outcomes.”

I’m dubious of how clinically important that finding is given that they are talking about half of the explained stillbirths, which comprise only a third (675/1,996) of all the stillbirths. And the stillbirths data gets even more problematic.

A miscarriage was defined as a pregnancy loss before the 28th week until 2004, when the definition changed to a pregnancy loss before the 22nd week. Aside from the 1,996 stillbirths mentioned already, the study reported 73,406 miscarriages, at a rate of 8.8 miscarriages per 100 (subsequent) pregnancies. Yet any pregnancy losses that occurred between the 22nd and 28th week were considered miscarriages for 22 years and stillbirths for the remaining 6 years – and C sections were associated with an *increased* risk of stillbirths and a *decreased* risk of miscarriages. See the problems here?

The researchers also lacked data on the women’s risk factors for ectopic pregnancies: the number of previous sexual partners, history of pelvic inflammatory disease, and age at first intercourse. All this missing data therefore cannot be calculated into their risk model which *already* shows an incredibly tiny increased risk.

The authors do explain multiple variations they did in their biostatistical analysis to address these limitations (such as doing exploratory analyses to look for inconsistencies), but there is only so much that can be done to account for these challenges in the dataset while retaining the integrity of the data and the analysis.

Further, there are other confounders the researchers did not account for at all or even address in their limitations. There was no data on family history of miscarriages, stillbirths or ectopic pregnancies, and they did not collect data on the mother’s age during her second pregnancy or any complications she had then (diabetes, obesity, high blood pressure).

What does all of this leave us with? We have a study showing us an extremely tiny increased risk for stillbirths and ectopic pregnancies among moms with first-time C sections (yet a mysterious decreased risk of miscarriages), with borderline statistical significance – as long as we disregard a huge chunk of information that wasn’t available but that could have completely changed the way the numbers were crunched and any remote, subsequent clinical importance. I assume there are ways this study contributes to the research literature for those deeply embedded in studying this – though I’m not sure how – but for us laypersons, it doesn’t mean much of anything.

 

*Yes, C section rates are too high, but I tire of seeing all the “negatives” of C sections being pounded into women’s heads so often, which only makes women who need medically indicated C sections feel bad.

5 Responses to “Keeping a study in perspective: C sections, stillbirth & ectopic pregnancy”

  1. You’re beating me to the post again! I was just sat in my lab reading this paper and thinking of writing about it but you’ve done a great job already!

    Get past the 14% (meaningless) headline and I think this study is actually pretty reassuring. As I’ve heard many many dire warnings about the risks of C-sections, many of them over hyped or completely made up. This study actually shows that the risks are far lower than many people think.

    There doesn’t seem to have been much press coverage of it over here yet, will be interesting to see what happens as the UK press usually jump all over anything with a too posh to push angle!

    SB

    • Tara Haelle

      Ha! Great minds and all that :) I agree: the study IS reassuring. I probably should have said as much, but I was too caught up in explaining what the numbers meant. I was really annoyed it was even published with the apparent conclusions it has.

  2. Young CC Prof

    You know, I had a c-section precisely because my son was at very high risk of stillbirth, due to a fun combination of two relatively common pregnancy complications. There’s a good chance that at least one of these complications would strike again in a future pregnancy, putting me at, (that’s right!) risk of stillbirth.

    As a general rule, when someone claims, “We controlled for all the confounders we could think of, and there’s still a small, barely statistically significant relationship!” I tend to be unimpressed.

    • Tara Haelle

      Yup, you hit the nail on the head. An association is just that — and association, and it’s likely that any associations here are related to underlying conditions. Unfortunately, that message doesn’t get out often when these sorts of studies are covered in the mainstream media.

  3. Supermouse

    Not to mention, when a woman has a Csection, the focus is on saving the current baby in utero (and/or the mother herself) and not worrying about potential future babies. Most people wouldn’t sacrifice the first child, by avoiding a life-saving Csection, in an effort to reduce the miniscule risk of a future ectopic or even stillbirth. Even if the risk was more significant, I think most people would be focusing on the life of the child about to be born and not thinking of hypothetical future children.

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