In this blog for pregnant women, Emily Carter, Cochrane UK Fellow and Obstetrics and Gynaecology Registrar, looks at the latest Cochrane evidenceCochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. on Vitamin D supplementation in pregnancy and how it may help reduce risks for mums and babies in the UK. This blog is part of a series called ‘Maternity Matters’, you can read the rest here.

What we already know

Vitamin D forms from sunlight on the skin and is used by the body to absorb calcium, needed for healthy bones and teeth. Up to half of all pregnant women in the UK are affected by vitamin D deficiency, which is more common in winter than in summer. Vitamin D deficiency disproportionately affects black and minority ethnic groups, those who cover their skin, those who are overweight and those with chronic illnessA health condition marked by long duration, by frequent recurrence over a long time, and often by slowly progressing seriousness. For example, rheumatoid arthritis., and particular care should be taken to advise these women (National Institute for Health and Care Excellence, 2019).

Pregnant women who are deficient in vitamin D (blood serum level <50nm) are more likely to have pregnancy complications including pre-eclampsia, diabetes, preterm birth and small babies. Babies born with vitamin D deficiency may have affected bone growth or in severe cases rickets (flexible bones). Vitamin D deficiency has also been linked with the development of childhood allergy (European Food SafetyRefers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. Authority, 2016; Royal College of Obstetricians & Gynaecologists, 2014).

An evidence gap

Whilst the Royal College of Obstetricians and Gynaecologists (RCOG) supports supplementing pregnant women with vitamin D (Royal College of Obstetricians & Gynaecologists, 2014), until now there has been a lack of evidence confirming the benefits and harms of this. In practice, it has been confusing what to advise women – should they be given a low dose supplement, a high-dose supplement, or should they be tested for vitamin D deficiency and treated if deficient in this important nutrient?

Although most pregnancy multivitamins contain 10 micrograms (400 international units), for women at high riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of vitamin D deficiency this may not be enough and they might benefit from a higher dose supplement. The criteria for who precisely who should be considered high riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. is unclear. In practice, local guidelines have used ‘common sense’ criteria, recommending a higher dose in women with some chronicA health condition marked by long duration, by frequent recurrence over a long time, and often by slowly progressing seriousness. For example, rheumatoid arthritis. illnesses and those who are less likely to absorb vitamin D from sunlight on the skin; but this has not been convincingly evidence-based so far (NHS Oxfordshire Clinical Commissioning Group, 2017; Royal College of Obstetricians & Gynaecologists, 2014).

It is also not clear what dose is required to gain the benefit of supplementation. There is also the issue of potential harms – we need to know what the best available evidence is about the possibility of harm from treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. in order to counsel women about the safetyRefers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. of taking pregnancy supplements.

What does the new Cochrane evidence add?

An important new Cochrane reviewCochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. update (Palacios et al., 2019) summarises the evidence base for Vitamin D supplementation in pregnancy; it includes 30 research studies and over 3700 pregnant women were included. Before this review, we knew that babies from mothers who lacked vitamin D have poorer outcomesOutcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’., but it had not been convincingly demonstrated that supplementation improved outcomesOutcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’. for those at riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent..

It showed that taking vitamin D supplements in pregnancy:

• Probably reduces the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of getting pre-eclampsia and gestational diabetes
• May reduce the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of having a low-birthweight baby.
• May reduce the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of severe bleeding after birth.
• May make no difference to the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of preterm birth before 37 weeks

Only one of the studies looked at whether there was any harm from taking vitamin D and nothing certain was shown.

Taking vitamin D and calcium supplements together in pregnancy: what does the evidence say?

 The review also shows that women who take vitamin D and calcium together in pregnancy probably have a reduced riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of developing pre-eclampsia. However, there may be an increased riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of preterm birth less than 37 weeks. These results warrant further research.

Whilst there are potential harms of taking combined calcium and vitamin D supplementation, the benefits for those at riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of pre-eclampsia may outweigh these harms. Women considering this should discuss with their midwife and obstetrician in early pregnancy.

What questions do we still have left to answer?

Should all women be screened for vitamin D deficiency?

There is no evidence supporting the use of universal screening for vitamin D deficiency in pregnancy, or telling us which groups of women this might be most useful for. The Royal College of Obstetricians and Gynaecologists recommends screening for very high-risk women, for instance those with symptoms, brittle bones, or those with chronic illnessA health condition marked by long duration, by frequent recurrence over a long time, and often by slowly progressing seriousness. For example, rheumatoid arthritis. who may not be able to absorb vitamins from the intestines. Many local guidelines follow this advice (NHS Oxfordshire Clinical Commissioning Group, 2017). This is ‘common sense’ practice but it is not convincingly evidence-based.

What dose of vitamin D supplementation is safe in pregnancy?

The effects and safetyRefers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. of different vitamin D supplementation regimens in pregnancy is the topic of a forthcoming Cochrane reviewCochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research..*

Where does this leave you?

Pregnant women may require higher doses of some vitamins, including vitamin D, from conception or early pregnancy. The RCOG recommends supplementing all pregnant women with vitamin D and high-risk women with high dose vitamin D. By booking the pregnancy on time, your community midwife can advise you early on to get the full benefit of treatmentSomething done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes..

There is now moderate-certaintyThe certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty.  Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach evidence that vitamin D supplementation probably reduces common risks associated with pregnancy including pre-eclampsia and gestational diabetes, and low-certaintyThe certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty.  Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach evidence that supplementation may reduce the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of having a low-birthweight baby or bleeding after birth.

There is now moderate-certaintyThe certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty.  Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach evidence that vitamin D and calcium supplementation probably reduces the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of pre-eclampsia. However, as there is low-quality evidence that this may increase the riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of pre-term delivery, this riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. should be discussed with your midwife or obstetrician, as further research is required to clarify this riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent..

What can be done to spread the message?

This latest evidence, which now gives greater certainty that vitamin D supplementation is probably beneficial in reducing some common risks associated with pregnancy, may be helpful in informing any planned updates of existing UK and international guidelines and their local implementation by NHS Clinical Commissioning Groups.

Development of patient information leaflets and online information which can be read at home can facilitate discussion with your obstetrician and midwife regarding individualised pregnancy risks and which supplements will be of most benefit.

The development of a clinical calculator to assess each woman at her first antenatal booking appointment for the need to take vitamin D, aspirin, calcium, high-dose folic acid and low molecular weight heparin (blood thinning injections for those at high riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of a blood clot) would help reach those women who may not know they could reduce their pregnancy riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. by taking these supplements or treatments early on in pregnancy.

*When the Cochrane ReviewCochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. on vitamin D supplementation regimens in pregnancy is published, this blog will be updated to report on the evidence.

Join in the conversation with @CochraneUK @Emily_Carter88 #MaternityMatters or leave a comment on the blog.

References may be found here.

Emily Carter has nothing to disclose.