A study was published in the journal “Birth Defects Research” on 25th January 2018 (Ref 1). A press release accompanied it (Ref 2) claiming that “women with low carbohydrate intake are 30 percent more likely to have babies with neural tube defects, when compared with women who do not restrict their carbohydrate intake.” Newspapers worldwide reported the story (Ref 3), reiterating the scary headline that “Women on low carb diets may be at 30 percent greater risk of having a baby with a spinal and neurological birth defect, according to a new study.”

One of my lovely subscribers, Belinda Fettke, alerted me to the article and asked me to take a look at it as my weekly newsletter. So I did. It was a case control study. It was fundamentally flawed in a number of ways:

1) The characteristics table compared the control with the control, not the control with the cases.

2) The ‘correct’ characteristics table was available, as a Supplemental, but neither table included important data related to the study – not least carbohydrate and folate/folic acid intake.

3) Consequently the study did not adjust for material differences between the control and case groups.

4) The study could not make the conclusion that it did.

I sent the email below to the authors on 30th January and sent a copy to the journal editor. I was minded to wait until I received a reply before posting this openly, but I have been asked to post this by a number of people who know that I found retraction-level errors because the headlines generated by this article need to be countered immediately. Pregnancy is worrying enough for women and men without fabrications like this trying to scare the life out of them.

Dear Dr Desrosiers,

I am currently reviewing your very interesting paper “Low carbohydrate diets may increase risk of neural tube defects.”

The article abstract reported “To assess the association between carbohydrate intake and NTDs [Neural tube defects], we analyzed data from the National Birth Defects Prevention Study from 1,740 mothers of infants, stillbirths, and terminations with anencephaly or spina bifida (cases), and 9,545 mothers of live born infants without a birth defect (controls) conceived between 1998 and 2011.” The article reported that these numbers became 1,559 (cases) and 9,543 (controls) with valid exclusions. That’s fine.

Table 1 reported the characteristics of the control group only. Table 1 should show the differences between the cases and the controls, not least so that it is known what to adjust for. Supplemental Table 1 reported this data.

Q1) Please can you explain why Table 1 is in the main paper and not Supplemental Table 1?

Q2) Please can you add the carbohydrate intake data to Supplemental Table 1 and please can you add the folate/folic acid intake data to Supplemental Table 1? These are standard inclusions in the characteristics table, so that readers can review, prima facie, the hypothesis being tested.

Q3) Please can you add the calorie intake data to Supplemental Table 1, as this has been adjusted for, but not reported anywhere?

Q4) Please can you provide the p values for Supplemental Table 1?

Q5) Working on the assumption that case/control ratios outside 0.9-1.1 are likely to be statistically significant, Supplemental Table 1 suggests that adjustments should have been made for (I have used a (Y) and a (X) to indicate what was/wasn’t adjusted for): maternal race/ethnicity (Y); maternal birthplace (X); education (Y); household income (X); BMI (X); smoking (X); alcohol use (Y); folic acid antagonist medication use (X); and study centre (Y).

Please can you explain why the factors marked with an (X) weren’t adjusted for?

Q6) If I interpret Table 2 correctly, it means that of the 1,559 cases, 93 restricted carbohydrate (6%) and 1,466 (94%) didn’t and it means that 479 controls (5%) restricted carbohydrate and 9,064 (95%) didn’t.

The study “hypothesised that some women who restrict carbohydrates may have suboptimal folate status and subsequently may be at higher risk of having an NTD-affected pregnancy.”

Notwithstanding that you set out to prove a hypothesis (and not to disprove the null), please can you confirm that you failed to prove this hypothesis? Table 2 could conclude that “94% of NTD-affected pregnancies occurred in women not restricting carbohydrate.” Table 2 could also conclude that “of the women who had an NTD-affected pregnancy, fractionally more (1 in 100) restricted carbohydrate.” Table 2 cannot conclude the other way round – that those who restrict carbohydrates may be at higher risk of having an NTD-affected pregnancy.

Q6) Having added carbohydrate intake, folate/folic acid intake, calorie intake and p values to Supplemental Table 1, please can you adjust for all the differences between cases and controls and then re-calculate the odds ratios accordingly?

Please can you then revise and reverse the directionality of the press release and correct the newspaper articles world-wide, which reported that: “women with low carbohydrate intake are 30 percent more likely to have babies with neural tube defects, when compared with women who do not restrict their carbohydrate intake.”

Many thanks

Kind regards – Zoë

{N.B. Neural tube defects (NTDs) include conditions such as spina bifida (malformations of the spine and spinal cord) and anencephaly (absence of major portions of the brain and skull), which can lead to lifelong disability and/or infant death.}

The full dissection of the article is available below to supporters… (research/nutrition ‘junkies’ may enjoy the notes!) Just login to read in full.