Preclampsia /eclampsia is one of the leading causes of maternal death throughout the world. The WHO currently recommends calcium supplementation for the prevention of pre eclampsia and eclampsia in areas where calcium intake is low1 2. These recommendations are an important first step in preventing the disorders but leave many questions unanswered. MI/Cornell University’s FAQs for calcium supplementation are an important next step for countries and organizations looking to work to implement prenatal calcium supplementation to save lives.
Hypertensive disorders of pregnancy (also called pregnancy-related hypertension) are defined as presence of elevated blood pressure with systolic pressure>140mmHg and/or diastolic pressure>90mm Hg during pregnancy. Pregnancy-related hypertension is a spectrum of conditions including chronic hypertension, gestational hypertension, preeclampsia, and eclampsia with varying management approaches rather than a specific diagnosis.
Specific diagnosis of the conditions across this spectrum depends on the onset of hypertension in relation to pregnancy as well as the presence of protein in urine (proteinuria). When onset of blood pressure elevation precedes the 20th week of pregnancy, a diagnosis of ‘chronic hypertension in pregnancy’ is made. Blood pressure elevation occurring after the 20th week of pregnancy in a woman previously known to have normal blood pressure is termed ‘gestational hypertension’. When significant protein is found in the urine (greater than 3g/24hr or dipstick>2) in addition to gestational hypertension, ‘pre-eclampsia’ is said to occur. The occurrence of convulsions or coma in a woman with preeclampsia is known as eclampsia (after ruling out other common causes of convulsion and/or coma).
Preeclampsia and eclampsia are the most dangerous hypertensive disorders of pregnancy. The underlying cause and biological processes leading to the symptoms of preeclampsia and eclampsia are not well understood. It probably is caused by multiple factors in both the mother and the fetus. Women are at higher risk of these conditions if the mother is very young (teenager), is having a first pregnancy after 35 years of age, is obese, is carrying twins, has Diabetes or has history of pre-eclampsia either in herself or in her family. The only known cure for these conditions is delivery of the placenta. This usually raises a dilemma in management of these conditions because preterm birth is the number one reason that babies die in the first month of life.
Hypertensive disorders of pregnancy are the 2nd leading cause of maternal mortality (pregnancy-related deaths) globally, and in addition, causes suffering to women and their families. Pre-eclampsia and eclampsia complicate about 2-8% of all pregnancies globally. About one out of every four maternal deaths in Latin America and the Caribbean, and about one out of every 10 maternal deaths in Africa and Asia have been attributed to pre-eclampsia and eclampsia.
Recent systematic reviews and meta-analyses have reported that pregnant women taking at least 1 gram of supplemental calcium daily reduced their risk of developing hypertensive disorders by approximately half, with the effect varying largely by habitual calcium consumption and underlying risk of preeclampsia. The largest protective effects were found in populations with habitual calcium consumption less than 900 mg and clinical categories considered as having high risk of pre-eclampsia.
The World Health Organization recommends routine daily supplementation of 1.5 - 2 grams of elemental calcium for all pregnant women in populations with low calcium intake, particularly women at high risk of preeclampsia. Risk factors for preeclampsia include teenage pregnancy, elderly primigravida (first pregnancy after 35 years of age), maternal obesity, multiple gestation (e.g. twins), diabetes and family/prior obstetric history of pre-eclampsia.
Low habitual calcium intake is defined as average habitual calcium intakes less than 900 mg of calcium per day. To illustrate this amount in terms of foods, 900 mg calcium could be provided by 3 cups (750 mL) of milk, or three servings of hard cheese such as cheddar, or 9 cups (more than 2 L) of cooked greens such as kale.
Routine administration to all pregnant women is advised when mean daily consumption is less than 900mg Ca/day in a population. Habitual calcium intake is poorly characterized in many developing countries. In settings where it has been studied, it has usually been found to be less than 900 mg except in few notable cases. Even high-income countries may not have habitual calcium intakes of 900 mg of calcium daily. It is reasonable to assume that the average population consumption is less than 900mg daily unless local studies are available and indicate otherwise.
The World Health Organization recommends starting supplementation at 20 weeks of gestation, because the research studies that have shown benefits started supplements in mid-pregnancy. Based on what we know about the processes involved in preeclampsia, there might be extra benefit in starting supplementation earlier in pregnancy. There are on-going research studies investigating the feasibility and impact of initiating supplementation in the first few weeks of pregnancy.
There are currently no limits on the duration of calcium supplementation. It is recommended that supplementation continue through delivery.
The World Health Organization recommends daily supplementation with 1.5 - 2 g of elemental calcium, based on the range of dosages administered in the clinical trials undertaken to date. At this point, scientists do not know the minimum effective dosage or optimal dosage for an individual patient.
There are no current recommendations about the best time of day to take calcium supplements. However, calcium is absorbed better when supplements are taken in smaller (<500 mg) divided doses, for example in the morning and evening, rather than taking the whole dose all at once.
Systematic reviews have reported that calcium supplementation may also improve bone mineral density in the infants of supplemented mothers, and reduce the risk of death for babies in the first month of life in developing countries.
The latest systematic reviews of all the benefits and risks of calcium supplementation in pregnancy found a marginally elevated risk of a rare syndrome (HELLP, which stands for Hemolysis, Elevated Liver enzymes, Low Platelet Count) in calcium-supplemented women in two studies. The importance of this finding is not clear given the extremely low number of cases (less than 10 women out of over 12,000 participants) and the ways that different health care systems diagnose this condition.
Although there have been concerns about calcium supplements contributing to kidney stones, evidence from supplementation trials so far do not support an increased risk of kidney stones or other adverse side effects when calcium supplements are used as recommended.
Calcium comes in several forms, and the best choice among the types of calcium supplements depends on consumer preferences, and the balance between concern for cost and ease of supplement delivery.
Calcium carbonate and calcium citrate malate have few side effects and are absorbed well. Several other types of calcium supplements are also available, but most of these are absorbed less well, or less is known about their side effects in pregnant women.
Calcium carbonate is cheaper and less bulky than calcium citrate malate (i.e. the pills can be made smaller) but its absorption might be less than that of calcium citrate malate if not taken around meal times.
Calcium from food can also meet the needs of pregnant women. Calcium supplements are not a drug; rather they are useful to help meet the calcium demands of pregnancy in populations with habitually low calcium intakes. Consuming foods rich in calcium can also achieve this objective but in many areas of the world few calcium rich foods are commonly eaten every day. In many places, it may be difficult to rely solely on dietary changes to fill the dietary gap. Unlike other nutrients such as iron, excess calcium is not stored in the body in adults and increased absorption of calcium from the diet is the primary way that women meet the increased demands in pregnancy.
Some studies over short time periods (1-2 weeks) have found that when iron pills and calcium pills are taken together, less iron is absorbed. However, most long term studies of absorption did not show clinically significant negative effects on iron status. Taken together, these studies suggest that the body adapts to compensate for the inhibitory effects of calcium on iron absorption observed in the short-term. Therefore, taking iron-folic acid pills together with calcium supplements seems to be a reasonable way to reduce the complexity of taking more than one pill during pregnancy. Simpler protocols for taking calcium and iron pills together improve uptake and adherence by pregnant women.
Calcium is known to interact with a number of other drugs ranging from antibiotics to various classes of anti-hypertensive drugs. However, at this time there are no data or evidence to suggest that calcium interacts with typical anti-malarial drugs that are recommended for use during pregnancy. As in all instances, if other drugs are being used in pregnancy, a skilled care provider should be consulted about whether calcium supplements should be taken with other medications.
The cost of calcium supplements is generally higher than that of iron and folic acid but no systematic estimates of the cost of this intervention are currently available. The cost of implementing calcium supplementation as part of routine antenatal care would depend on many factors, including type of supplement used, effectiveness of existing healthcare delivery systems and local barriers to healthcare access.
Yes, currently available information and recommendations, such as this document, can be used to design functional programs and provide useful policy guidelines. However, because this is a new recommendation, further research will help to refine current recommendations and improve programs.
More specific research to further understand issues relating to nutrient-nutrient interactions, optimal dosage and optimal timing would be useful. Research on programmatic issues including cost and logistics of implementation, optimal delivery platforms, facilitation of adherence, and targeting mechanisms is ongoing and will inform programs.
The WHO has issued a strong recommendation for antenatal calcium supplementation to prevent preeclampsia and eclampsia based on current evidence that it can reduce maternal mortality and morbidity in developing countries. On-going research will help to refine the recommendation and its implementation, but evidence is sufficient to put policy and program plans in place now and make the most of this important opportunity to save lives.
More information is provided in the following references:
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