Maternal and health care determinants of preconceptional use of folic acid supplementation in France: results from the 2010 National Perinatal Survey
To estimate the national prevalence and analyse the factors associated with preconceptional folic acid supplementation, including maternal sociodemographic characteristics, region of residence, birth control use and chronic diseases requiring medical care before conception.
Cross-sectional population-based study.
All maternity units in France.
A nationally representative sample of women giving birth in 2010 (n = 12,646).
Data came from mothers' interviews 2–3 days after delivery. Statistical analyses included multivariable logistic regressions.
Main outcome measure
Folic acid supplementation starting at least 1 month before conception.
14.8% (95% confidence interval [95% CI] 14.2–15.4) of women used folic acid before pregnancy; this percentage varied from 10.4% to 18.7% across regions. Supplementation was more frequent in primiparae, French citizens, women with higher educational levels and those needing medical monitoring or treatment before conception. Women who stopped contraception to become pregnant (75% of our population) used folic acid more often (intrauterine device or implant: 19%, pill: 17%, other methods which did not need medical monitoring: 17%) than other women (7%). The adjusted odds ratios were 3.3 (95% CI 2.6–4.3) for intrauterine device and implant, 2.2 (95% CI 1.8–2.6) for pill and 1.9 (95% CI 1.5–2.4) for other methods, compared with women who did not use birth control.
The absence of preconceptional folic acid supplementation for most women, even those needing consultations with healthcare professionals before pregnancy, shows that campaigns to promote folic acid supplementation should address not only women but also healthcare professionals involved in birth control and obstetric care before pregnancy.
Neural tube defects (NTDs) are severe congenital malformations of the central nervous system, with a prevalence of approximately 1 per 1000, which lead to stillbirths, neonatal deaths and neurological disabilities. Termination of pregnancy is proposed to women in many countries, and 77% of pregnancies affected by NTDs were terminated in the early 2000s in Europe.
The efficacy of folic acid supplementation for primary prevention of NTDs is well established by several randomised controlled trials and a meta-analysis of these studies. Daily folic acid doses ranging from 0.4 to 4 mg, before pregnancy and for up to 12 weeks of gestation, decrease the risk of NTDs by up to 72% (relative risk 0.28; 95% confidence interval [95% CI] 0.15–0.52). Assuming a 50% efficacy rate, a conservative estimate of the number of cases avoided would be 450 per year in France.
Most European countries have issued recommendations for folic acid supplementation, with or without a folate-rich diet, during the periconceptional period. In France, it is recommended that women who intend to have a pregnancy begin folic acid supplementation at least 1 month before conception. Recommendations in Europe have generally had little if any effect on the trends in total prevalence of NTD since the 1990s, however.[4, 5] Numerous studies have estimated the frequency of folic acid use, but population-based studies are rare, especially at the national level,[6, 7] and almost never based on a representative sample of births. It is therefore difficult to know the extent to which recommendations have been adopted in the overall population of pregnant women. Moreover, studies of the determinants of folic acid intake have rarely considered the role of the medical providers consulted before conception.[9, 10] We hypothesised that, in addition to maternal sociodemographic characteristics, healthcare providers can play an important role in women's decision to use folic acid supplementation before pregnancy. To test this hypothesis, we examined the prevalence of folic acid use for women who had to have specific medical visits before pregnancy. These women included, for example, those who had conceived following fertility treatments and those who had an intrauterine device (IUD).
Using population-based data from a representative national sample of women giving birth in France, we sought to estimate the prevalence of folic acid supplementation begun before conception and to analyse the factors related to this supplementation, while distinguishing three categories of determinants: (i) maternal sociodemographic characteristics and region of residence, (ii) contraceptive methods and (iii) diseases or complications requiring medical visits or treatments before conception.
Our study was based on data from the 2010 French National Perinatal Survey. National Perinatal Surveys are routine surveys designed to monitor perinatal health, medical care and health behaviour. They include all births (live and stillbirths) during a 1-week period in all maternity units. Women are interviewed in the maternity unit 2 or 3 days after delivery about their sociodemographic characteristics, health behaviours, birth planning and fertility treatments. Data on maternal health are collected from medical records. Comparisons for several perinatal indicators (e.g. maternal age, gestational age) available in birth certificate statistics and hospital discharge statistics show that the sample is representative of all births in 2010.
In the 2010 survey, we asked women for the first time about folic acid use: ‘Did you use folic acid or vitamin B9 for prevention of NTDs for this pregnancy?’ If they answered yes, we asked them: ‘When did you start: more than 3 months before conception, between 1 and 3 months before conception, first month of pregnancy or after the first month?’
After exclusion of births in overseas territories and migrants who arrived during or in the 6 months before pregnancy, our sample included 14,266 women; 664 (4.6%) of them were not interviewed and 956 (6.7%) women did not know if they had used folic acid or when they began it. Finally, we analysed data for 12,646 women.
We first assessed the prevalence of folic acid supplementation before conception and then studied the factors associated with it, comparing women who used folic acid supplementation before conception with those who did not or who started after conception. We studied three categories of determinants: (i) maternal characteristics, which included sociodemographic characteristics, smoking before pregnancy, body mass index and region of residence, (ii) birth control and (iii) fertility treatments and chronic diseases.
Body mass index was studied because high prepregnancy body mass index is associated with an increased risk of NTDs. Pregnancy was considered planned if the woman stopped using her last contraceptive method to become pregnant and wanted a baby at the time she became pregnant. Birth control methods were categorised according to the need for medical services. We distinguished implants and IUD, which must be removed by a medical doctor, birth control pills, which require routine medical visits, and the other methods (mainly condom), which do not need medical visits. Three categories of chronic diseases or perinatal risk factors were considered, according to the woman's need for medical care and monitoring before conception. The first category included those that necessitated folic acid supplementation, or a medical visit before pregnancy to adapt treatment or for screening (methylenetetrahydrofolate reductase mutation, previous pregnancy affected by NTDs, epilepsy, autoimmune diseases, HIV or hepatitis B virus infection, diabetes mellitus and recurrent miscarriages). The second category included maternal diseases that require regular medical follow up, such as high blood pressure, thyroid diseases, or a history of cancer. The third category included previous adverse pregnancy outcome or complications, including fetal or neonatal death, preterm birth, small-for-gestational-age newborn, gestational diabetes and gestational hypertension.
Chi-square tests were performed in the bivariable analyses and logistic regressions for multivariable analyses. Data were analysed with sas 9.2 (SAS Institute Inc., Cary, NC, USA).
Folic acid use began more than 3 months before pregnancy for 6.6% of women, and 1–3 months before pregnancy for 8.2%. In all, 14.8% (95% CI 14.2–15.4) of women started folic acid supplementation before pregnancy. Another 11.7% of women started folic acid use during the first month of pregnancy.
Folic acid use before pregnancy was more frequent in older women, married or cohabiting women, European women, those who did not smoke or had stopped smoking for pregnancy and women with a body mass index <25 (Table 1). Folic acid use was higher in women with low parity and high educational level and varied from 10.4% in the Mediterranean region to 18.7% in the western region.
Table 1. Prevalence of folic acid use before pregnancy according to womens' characteristics
|Age|| || || ||<0.0001|
|<25 years||2051||6.9||5.8–8.1|| |
|25–29 years||4238||15.1||14.0–16.2|| |
|30–34 years||3941||17.4||16.2–18.6|| |
|≥35 years||2403||16.8||15.3–18.3|| |
| ||(12,633)|| || || |
|Parity|| || || ||<0.0001|
| ||(12,592)|| || || |
|Marital status|| || || ||<0.0001|
|Cohabiting, married||5804||16.5||15.6–17.5|| |
|Cohabiting, not married||5975||14.4||13.6–15.3|| |
| ||(12,630)|| || || |
|Educational level|| || || ||<0.0001|
|Middle school or less||3348||6.5||5.7–7.4|| |
|High school||2489||9.9||8.7–11.1|| |
|Some college||2760||17.0||15.6–18.4|| |
| ||(12,598)|| || || |
|Nationality|| || || ||<0.0001|
|From other European countries||329||18.8||14.8–23.5|| |
|From North African countries||490||8.2||5.9–11.0|| |
|From other African countries||276||7.6||4.8–11.4|| |
|From other countries||207||17.4||12.5–23.3|| |
| ||(12,640)|| || || |
|Smoking before pregnancy|| || || ||<0.0001|
|Stopped before pregnancy||334||24.0||19.5–28.9|| |
| ||(12,622)|| || || |
|Body mass index|| || || ||<0.0001|
| ||(12,422)|| || || |
|Region of residence|| || || ||<0.0001|
|Metropolitan area||2875||18.0||16.6–19.4|| |
|Paris Basin||2047||11.1||9.8–12.5|| |
| ||(12,646)|| || || |
Folic acid use was more frequent in women who had stopped their contraception because they wanted to become pregnant, women who had had fertility treatment and those who had a chronic disease that required pregnancy planning or routine medical follow up (Table 2). The level of use was particularly higher in women with fertility treatment; for instance, 56.8% of the women who had in vitro fertilisation took folic acid before pregnancy. On the other hand, the prevalence of folic acid supplementation never exceeded 20% among women who stopped contraception or those with chronic disease or previous adverse pregnancy outcome.
Table 2. Prevalence of folic acid use before pregnancy according to pregnancy planning
|Birth control method stopped to become pregnant|| || || ||<0.0001|
|IUD or implant||820||19.2||16.5–22.0|| |
|Other methods||869||17.0||14.6–19.7|| |
|No method or method stopped for other reasons||3094(12,247)||7.3||6.4–8.2|| |
|Infertility treatment|| || || ||<0.0001|
|In vitro fertilisation||301||56.8||51.0–62.5|| |
|Artificial insemination||119||37.0||28.3–46.3|| |
|Ovulation induction only||298||26.2||21.3–31.6|| |
|Maternal diseases/perinatal risk factors|| || || ||0.0204|
|Diseases needing pregnancy planning||240||19.2||14.4–24.7|| |
|Diseases needing routine medical examinations||784||17.7||15.1–20.6|| |
|History of adverse obstetric outcome||957||14.3||12.2–16.7|| |
| ||(12,646)|| || || |
In the multivariable analysis, the adjusted odds ratio (OR) was 3.5 (95% CI 2.5–5.0) for nulliparous women compared with those with parity of at least three; it was 2.8 (95% CI 2.3–3.4) for women with a postgraduate degree compared with women who did not go beyond middle school, and 2.1 (95% CI 1.7–2.6) in the western region compared with the Mediterranean region (Table 3).
Table 3. Crude and adjusted associations of folic acid use before pregnancy with women's characteristics, region of residence and pregnancy planning
|Cohabiting, not married||0.9||0.8–0.9||0.9||0.8–1.1|
|Middle school or less||1||–||1||–|
|From other European countries||1.3||1.0–1.7||1.4||1.0–1.9|
|From North African countries||0.5||0.4–0.7||0.7||0.5–1.0|
|From other African countries||0.5||0.3–0.7||0.8||0.4–1.3|
|From other countries||1.2||0.8–1.7||1.0||0.7–1.6|
|Smoking before pregnancy|
|Stopped before pregnancy||1.6||1.2–2.1||1.4||1.1–1.9|
|Region of residence|
|Birth control method stopped to become pregnant|
|IUD or implant||3.0||2.4–3.8||3.3||2.6–4.3|
|No method or method stopped for other reasons||1||–||1||–|
|In vitro fertilisation||8.6||6.8–10.9||7.2||5.5–9.4|
|Ovulation induction only||2.3||1.8–3.0||1.8||1.4–2.4|
|Maternal diseases/perinatal risk factors|
|Diseases needing pregnancy planning||1.4||1.0–1.9||1.7||1.2–2.5|
|Diseases needing routine medical examinations||1.3||1.0–1.5||1.2||1.0–1.5|
|History of adverse obstetric outcome||1.0||0.8–1.2||1.6||1.3–2.0|
Women who stopped contraception to get pregnant used folic acid more often than those who did not: adjusted OR 3.3 (95% CI 2.6–4.3) after an IUD or implant, 2.2 (95% CI 1.8–2.6) after oral contraception, and 1.9 (95% CI: 1.5–2.4) after use of methods not requiring medical follow up. Maternal diseases and previous adverse pregnancy outcome were also significantly associated with folic acid use, but the adjusted ORs were <2.
In a nationally representative sample of women giving birth in France, we found that the percentage of women using preconceptional folic acid was 15% and varied substantially across regions. Folic acid supplementation was notably higher among women undergoing fertility treatments, and somewhat higher among those who used contraception, or who had diseases requiring medical care before conception. Nonetheless, the percentage of folic acid use was still <20% for women who had used a medical contraceptive method before planning a pregnancy.
Strengths and weaknesses
An important strength of our study is that our sample was representative of women giving birth in France and enabled us to assess folic acid use at both the national and regional levels. In addition, we had data about health status before pregnancy, fertility treatments and birth control methods. We could also estimate accurately the percentage of planned pregnancies. However, we could not assess whether folic acid was prescribed by a physician or obtained over the counter. Data on folic acid were based on women's reports after delivery; we may have underestimated folic acid use, as some women may have unintentionally consumed folic acid in multivitamin supplements or forgotten folic acid use. Moreover, we do not know for how long women took folic acid or their daily dose, although these data may have a substantial effect on the actual degree of compliance with guidelines. However, using a few simple questions on folic acid supplementation facilitates monitoring of its trends in routine National Perinatal Surveys with more general health objectives.
Despite guidelines in most countries, folic acid use before pregnancy has not become widespread in Europe. It seems to vary substantially across countries. In a representative national sample of births in Ireland, 64% of women took folic acid before conception compared with only 15% in our study. In the Netherlands, 37% of women in a multi-ethnic population in Rotterdam in 2002–06 and 65% of women attending some antenatal clinics in 2009 in the northern region started folic acid use before pregnancy.[13, 14] In national birth cohorts, this proportion was 30% in Denmark and 20% in Norway. However, these studies may have overestimated folic acid use because of selection bias with a higher likelihood of inclusion for women with higher educational levels and those with a strong interest in health issues. In other European countries, studies based on one or two maternity units showed consumption levels very often lower than 15%.[15, 16]
The women's educational level, their geographic origin, their family situation and their parity have been found to be associated with periconceptional folic acid use.[6-10, 14, 16-20] This may be explained by the lower importance attributed to prevention and limited access to medical information in less advantaged social classes. In particular, knowledge about folic acid is lower among women of lower social position and of high parity.[21, 22] Lower consumption among women with high parity, independently of their social characteristics, suggests that a previous pregnancy was not the occasion for informing, or in any case, convincing women of the importance of folic acid supplementation.
Planning pregnancy is an important condition for preconceptional folic acid use.[6, 7] Nonetheless, in our study, only 19% of the women who had to have a medical visit to remove their implant or IUD had taken folic acid, and only 17% of the women who had used birth control pills took folic acid, whereas a medical visit is required every 6 months in France to obtain a prescription. Moreover, the adjusted odds ratios did not differ very much between women who had used oral contraception and those who had used a method not requiring medical follow up. Hence, the medical consultations for contraceptive monitoring do not seem to have played a major role in the dissemination of folic acid prevention of NTDs.
Chronic diseases requiring specific care before pregnancy present another opportunity for prescribing folic acid. In our study, the fairly low prevalence of folic acid use among these women suggests that the medical visits did not have an important effect on folic acid use. On the other hand, the highest percentage of folic acid use in our population was observed among women who underwent in vitro fertilisation. French hospital fertility programmes usually include folic acid in the prescription for ovulation induction. This practice varies widely between countries[7, 14, 23] and it is chosen perhaps in part to increase the success rate of assisted conception techniques rather than specifically for the prevention of NTDs.
French guidelines on folic acid supplementation were issued in 1997 and in 2000, but very little has been done to promote these guidelines. Physicians were informed by the medical press in 2004, and by invitations to consult a website. A single information campaign is unlikely to increase folic acid use substantially. In the Netherlands, the policy promoting folic acid began in 1995 with press releases, and was then repeated with additional measures. This resulted progressively in a high level of folic acid use.[13, 18, 25] It also seems important to diversify the programmes, aiming especially at groups who are less aware of prevention.[25, 26]
The campaigns to promote folic acid should target specifically women planning their pregnancies. They accounted for about three-quarters of the women who gave birth in our study and also for a substantial proportion of women in other European countries.[6, 13, 14, 29] Information on folic acid should be provided to women during medical visits for contraception. The preconceptional consultation is another opportunity to inform women.[17, 30] Another measure is to prescribe oral contraception that contains folic acid. Most of these possibilities assume that physicians are convinced of the benefit of folic acid. Our results suggest, however, that, except for specialists in fertility, doctors may not have sufficiently encouraged women to use folic acid. Their active participation is important for increasing the overall folic acid use and reducing social disparities in its use, because healthcare professionals constitute an important source of information for women of lower socio-economic groups.
In face of low levels of supplementation despite the recommendations, a mandatory fortification policy is another possibility for increasing folic acid levels and would also help to limit socio-economic differences. Studies have shown a reduction in the prevalence of NTDs in countries that have established policies of fortification. Nonetheless, most European countries are reluctant to adopt this policy because, despite the beneficial effects of increasing vitamin B9 intake among women desiring pregnancy, fortification could have possibly harmful effects in the general population, although this is a topic of considerable controversy.[34, 35]
The substantial regional and social disparities in folic acid supplementation show the value of assessing national campaigns to promote folic acid supplementation using nationally representative data, and not simply at a maternity unit or in a limited geographic zone. In France, few women, even those with regular medical care (as for oral contraception), take folic acid before conception. Campaigns to promote folic acid supplementation should address not only women, but also healthcare professionals involved in birth control and obstetric care. These campaigns should be conducted in conjunction with studies on the knowledge, attitudes and actions undertaken by healthcare professionals regarding preconceptional folic acid use.
The authors thank the Maternal and Child Health service in each French district, the heads of the maternity units, the investigators and all of the women who participated in the survey. Inserm Unit 953 has received a grant from the Bettencourt Foundation (Coups d'élan pour la Recherche française) in support of its research activities.
Disclosure of interests
The authors have no conflict of interest to declare.
Contribution to authorship
JT analysed and interpreted the data, and wrote the first draft of the manuscript. NL and BK participated in the discussions on the analysis and interpretation of the results and made substantive suggestions for revision of the manuscript. CP participated in the analysis and interpretation of the results. BB contributed to the design of the study and of the National Perinatal Survey, interpreted the results and revised the article.
Details of ethics approval
The survey was approved by the National Council on Statistical Information (Comité du label) and the French Commission on Information Technology and Liberties (CNIL) (registration number 909003).
The Ministry of Health funded the survey and this study.