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Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems

  1. G Justus Hofmeyr1,*,
  2. Álvaro N Atallah2,
  3. Lelia Duley3

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 19 JUL 2006

Assessed as up-to-date: 1 MAR 2006

DOI: 10.1002/14651858.CD001059.pub2


How to Cite

Hofmeyr GJ, Atallah ÁN, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD001059. DOI: 10.1002/14651858.CD001059.pub2.

Author Information

  1. 1

    University of the Witwatersrand, University of Fort Hare, Eastern Cape Department of Health, Department of Obstetrics and Gynaecology, East London Hospital Complex, East London, Eastern Cape, South Africa

  2. 2

    Universidade Federal de São Paulo / Escola Paulista de Medicina, Brazilian Cochrane Centre, São Paulo, SP, Brazil

  3. 3

    University of Leeds, Centre for Epidemiology and Biostatistics, Bradford, West Yorkshire, UK

*G Justus Hofmeyr, Department of Obstetrics and Gynaecology, East London Hospital Complex, University of the Witwatersrand, University of Fort Hare, Eastern Cape Department of Health, Frere and Cecilia Makiwane Hospitals, Private Bag X 9047, East London, Eastern Cape, 5200, South Africa. gjh@global.co.za.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 JUL 2006

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Characteristics of included studies [ordered by study ID]
Belizan 1991

MethodsMulticentre trial. Numbered, sealed opaque envelopes, containing randomisation codes. Of 593 (calcium) vs 601 (placebo) enrolled, 14 vs 13 were lost before starting treatment and excluded from analysis; 577 vs 588 had at least partial follow up. Follow up was incomplete for 52 vs 46, but delivery data were available in 17 vs 12 of these, giving delivery data for 544 vs 554.


ParticipantsNulliparous women, < 20 weeks pregnant; blood pressure < 140/90 mmHg (mean of 5 measurements); no present or past disease; not taking medication; normal oral glucose tolerance tests.


Interventions2 g calcium as 500 mg calcium carbonate tablets, vs identical looking placebo tablets. Compliance was 84% (calcium) and 86% (placebo).


OutcomesGestational hypertension (DBP 90 or more; SBP 140 or more mmHg, on 2 occasions 6 hours apart); pre-eclampsia (gestational hypertension + proteinuria > 0.3 g/L on 2 random urine samples 6 hours apart); BP measured with random-zero sphygmomanometers, Korotkoff sound 5. Perinatal death.
Follow up: BP > 95th percentile for sex, age and height for children 5-9 years.


NotesThree hospitals in Rosario, Argentina. Data for preterm birth given as percentages, not clear what the denominators were. Assumed to be the numbers with complete follow up (527 vs 542) as these were the numbers which were divisible by the percentages to give whole numbers.

Babies born in the private hospitals followed up at 7 years. Of 614 randomised (calcium 309/placebo 305), 301/299 completed the first study, 2/6 infant deaths and 1/0 maternal deaths had occurred, leaving 298/293 eligible for follow up. 289/285 were contacted, 10/5 refused to participate, 22/19 lived outside the country, and 257/261 were assessed (88% of those eligible).


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate





CPEP 1997

MethodsNumbered treatment packs in computer-generated simple randomisation sequence. Loss to follow up: calcium 132/2,295 vs placebo 121/2,294.


ParticipantsPregnant nulliparas (45% black, 35% non-Hispanic white, 17% Hispanic white). Passed compliance test (took 75% of placebo over 6-14 days); BP 134/84 mmHg or less; urine protein dipstick negative or trace; 13-21 weeks pregnant.

Exclusion criteria: taking medications; obstetric or pre-existing diseases or personal characteristics which could influence study end-points, absorption or metabolism of calcium; any risk associated with calcium supplementation, or compliance; elevated serum creatinine (1.0 mg per decilitre or more) or calcium (10.6 mg per decilitre or more); renal disease; haematuria; history or family history of urolithiasis; frequent use of calcium supplements or antacids.

Of 11,959 women screened, 5,703 excluded initially and a further 1,667 after the compliance test. The remaining 4,589 women were enrolled.


Interventions2 g/day elemental calcium as calcium carbonate, or placebo. Taken until delivery, development of pre-eclampsia or suspicion of urolithiasis. All women took 50 mg calcium per day as normal supplementation and were asked to drink 6 glasses of water per day.

Compliance was 64% in the calcium group and 67% in the placebo group. 20% of women took > 90% of the allocated treatment.


OutcomesGestational hypertension (DBP sitting, fifth Korotkoff sound unless zero, 90 mmHg or more on 2 occasions, 4 hours-1 week apart); severe gestational hypertension (DBP 110 mmHg twice or treated, or complications); proteinuria (300 mg/24 hours or more, 1+ on 2 occasions 4 hours-1 week apart, 2+ or more, or protein/creatinine ratio 0.35 or more); pre-eclampsia (gestational hypertension + proteinuria within 7 days of each other); severe pre-eclampsia (50/2163 vs 59/2173); renal insufficiency (21/2163 vs 23/2173); urolithiasis (1/2163 vs 3/2173); prematurity (< 37 weeks); baby small for gestational age (124/2163 vs 105/2173); perinatal death.
A limited follow up of mothers and infants found reduced systolic blood pressure at two years of age in the calcium supplementation group (Mean 95.4 mmHg, SD 7.6, n = 35 vs 100.2, 7.9, n = 18). The data have not been included in this review because the low and unequal follow-up rate (35 and 18 from 497 invited to participate) limit the reliability of the results.


NotesMulticentre trial, 5 US university centres. Maternal outcomes reported as percentages of the whole number enrolled. In this review, denominators of 2,163 (calcium) and 2,173 (placebo) have been used. Neonatal outcomes in the report are based on live births (2134 and 2139). Addition of abortions and fetal deaths brings these numbers to 2156 and 2166. It is not clear why a discrepancy in numbers remains.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate





Crowther 1999

MethodsCentral telephone randomisation, stratified by
centre using variable blocks. Double-blind.


ParticipantsInclusion criteria: Nulliparous women; Singleton pregnancy; < 24 weeks' gestation; Blood pressure < 140/90 mmHg; expected to give birth at a collaborating centre.
Exclusion criteria: antihypertensive therapy; medical contraindication to calcium supplementation.


InterventionsCalcium carbonate 1.8 g daily or lactose placebo tablets, from 20-24 weeks till birth.


OutcomesPrimary: pregnancy-induced hypertension (diastolic blood pressure 90 mmHg or more on two consecutive occasions 4 hours apart, or 110 mmHg once; pre-eclampsia (as above plus proteinuria 0.3 g or more per 24 hours or 2+ protein or more on two random clean-catch urine samples); preterm birth (< 37 weeks).
Secondary: severe pregnancy induced hypertension (diastolic blood pressure 110 or more on 2 occasions 4 hours apart, or 120 or more once); severe pre-eclampsia (as above plus proteinuria); very preterm birth (< 32 weeks; extremely preterm birth (< 28 weeks); maternal fetal and infant events after trial entry.


NotesFive hospitals in Australia. August 1992 to December 1996.
Estimated sample size 948. Trial stopped prematurely for financial reasons.
31% in the calcium group and 24% in the placebo group stopped taking the tablets during the trial. Analysis was by intention to treat.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate





L-Jaramillo 1989

MethodsAssigned independently in sequence using a table of random numbers. All 106 women enrolled completed the study (calcium 55, placebo 51), 14 women who delivered at 36-38 weeks excluded (calcium 6, placebo 8), none developed gestational hypertension. These women are included in this review.


ParticipantsInclusion criteria: nulliparity; age 25 years or less; certain menstrual dates; clinic attendance before 24 weeks gestation; residence in Quito; normotensive; no medical disorders; not taking medication or vitamin/mineral preparations.


InterventionsCalcium supplementation with 4 calcium gluconate tablets daily, each containing 500 mg elemental calcium, from after 23 weeks' gestation till delivery, vs identical placebo tablets.


OutcomesGestational hypertension (BP 140/90 mmHg or more, or rise of 30 mmHg systolic or 15 mmHg diastolic, on 2 occasions 6 hours apart); weekly weight gain, mean (SEM) (calcium 412 (26) vs placebo 452 (28) g); birthweight (3097 (40) vs 2832 (50) g); length of gestation (39.3 (0.08) vs 38.7 (0.07) weeks).


NotesQuito, Ecuador (altitude 2800 m). 1984 to 1986. An earlier report of apparently the same study gave an incidence of gestational hypertension of calcium 3/46 vs placebo 13/46 (Lopez-Jaramillo 1987).


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearD - Not used





L-Jaramillo 1990

MethodsRandomised, double-blind trial. Stated "Each patient was assigned independently in sequence", and "All women completed the study".


ParticipantsHealthy nulliparous women with positive roll-over test at 28-30 weeks' gestational age - judged at high risk for gestational hypertension.


Interventions2,000 mg elemental calcium daily, from 28-32 weeks to delivery, vs placebo starch tablets.


OutcomesGestational hypertension (BP > 140/90 mmHg on 2 occasions 6 hours apart); proteinuria (300 mg/L); duration of pregnancy (calcium mean 39.2 (SD 1.2) vs placebo 37.4 (2.3) weeks); birthweight (2936 (396) vs 2685 (427) g).


NotesQuito, Ecuador (altitude 2800 m). Large discrepancy in size of groups not accounted for.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear





L-Jaramillo 1997

MethodsProspective, randomised, double-blind, placebo controlled trial. 14 withdrawals after randomisation: 12 by change to another hospital or private medical doctor, 2 by non-compliance. 9/134 (6.7%) were from the calcium group and 5/140 (3.6%) from the placebo group.


ParticipantsInclusion criteria: age < 17.5 years; nulliparous; first prenatal visit before 20 weeks' gestation; certain menstrual dates; residency in Quito for at least 1 year; BP =/< 120/80 mmHg; no underlying medical disorders; no drug, mineral or vitamin therapy. Average daily calcium intake in this population is 51% of the recommended dietary allowance.


InterventionsElemental calcium 2 g daily as calcium carbonate from 20 weeks (n = 134), versus placebo tablets (n = 140).


OutcomesPre-eclampsia (BP > 140/90 mmHg on 2 occasions > 6 hours apart, and proteinuria > 300 mg/L (> 1+ on dipstick on 2 occasions 4-24 hours apart). BP recorded as mean of 2 measurements, 2 minutes apart, in the right arm, in the sitting position (1st and 5th Korotkoff sounds).

Maternal serum ionised calcium at 38 weeks was calcium group mean 1.23, SD 0.02 mM vs placebo 1.16, 0.02; umbilical cord serum ionised calcium levels were calcium 1.44, 0.04 vs placebo 1,37, 0.03; gestational length was calcium 39.6, 0.4 versus placebo 38.7, 0.3.


NotesQuito, Ecuador (altitude 2800 m). 1990 to 1995.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate





Niromanesh 2001

MethodsDouble-blind, placebo controlled clinical trial. Women were "randomly assigned".


ParticipantsWomen at high risk for pre-eclampsia: positive 'roll-over' test and at least one risk factor for pre-eclampsia; 28-32 weeks' pregnant; blood pressure < 140/90 mmHg. Exclusion criteria: chronic medical conditions.
Not defined as low- or adequate calcium intake (from table 1 dairy intake appears to be about 200 ml + 400 g per day).


InterventionsElemental calcium 2 g daily (500 mg 6-hourly) or placebo, coded by the pharmacy.


OutcomesPre-eclampsia: an increase (30 mmHg) of systolic blood pressure above 14 mmHg and an increase (15 mmHg) of diastolic blood pressure above 90 mmHg, twice 4-6 hours apart, with proteinuria 1+; duration of pregnancy (39.5 SD 0.8 vs 37.7 SD 2.5 weeks); birthweight (3316 SD 308 vs 2764 SD 761 g); weekly maternal weight increase (no difference).


NotesNo loss to follow up.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate





Purwar 1996

MethodsProspective, randomised, double-blind, placebo-controlled trial. Allocated by means of a computer-generated randomisation list. After randomisation, 11/201 (5.5%) women lost to follow up (calcium 6, placebo 5).


ParticipantsCalcium intake mean 336 mg (calcium) and 352 mg (placebo group) per day.
Inclusion criteria: nulliparity; normal single viable pregnancy; known dates; antenatal clinic before 20 weeks; intending to deliver in the same institute; normal glucose tolerance test; no hypertension; no underlying medical disorders.

Exclusion criteria: renal disease; collagen vascular disease; chronic hypertension; endocrinological disease; taking medication.


InterventionsOral calcium containing 2 g elemental calcium daily (n = 103), compared with identical placebo tablets (n = 98), taken from 20 weeks.


OutcomesGestational hypertension (SBP > 140 mmHg and DBP > 90 mmHg, twice 6 hours apart) and pre-eclampsia (hypertension + proteinuria =/> 0.3 g/24 hours).


NotesNagpur, India.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate





S-Ramos 1994

MethodsDouble-blind placebo-controlled trial. Randomisation by computer-generated list. Outcome data entered before breaking the code. 4/33 allocated calcium lost to follow up.


ParticipantsNormotensive nulliparas; positive roll-over test (281/1065) and positive angiotensin II infusion test at 20-24 weeks' gestation (67/281).
Exclusion criteria: factors increasing the risk of gestational hypertension, including renal disease, collagen vascular disease, diabetes mellitus, chronic hypertension, multifetal pregnancy.


InterventionsCalcium supplementation with 2 g per day elemental calcium as 500 mg calcium carbonate tablets, versus identical placebo tablets. Compliance checked with electronic pillboxes. Compliance was 79% vs 81%.


OutcomesGestational hypertension (BP at least 140/90 mmHg on 2 occasions 4-6 hours apart, on bedrest in hospital); pre-eclampsia (gestational hypertension + proteinuria: 1+ or 300 mg/24 hours); severe pre-eclampsia (pre-eclampsia plus one of BP at least 160 mmHg systolic or 110 mmHg diastolic; proteinuria at least 5 g/24 hours; oliguria < 400 ml per day; elevated liver enzymes; thrombocytopenia < 100,000/microlitre; pulmonary oedema; severe epigastric pain).

Birthweight (calcium 3245 (SD 414) vs placebo 3035 (542) g); mean gestational ages (35.6 vs 34.4 weeks); 5 minute Apgar < 7 (1/29 vs 1/34); cord arterial pH (7.25 (0.07) vs 7.20 (0.07)); fetal growth impairment (2/29 vs 4/34).


NotesJacksonville, Florida, USA. University hospital serving low-income population.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate





Villar 1987

MethodsDouble-blind, randomised controlled trial. Random numbers in closed envelopes.


ParticipantsInclusion criteria: nulliparous or primiparous; known menstrual dates; age 18-30 years; singleton pregnancy; negative roll-over test.

Exclusion criteria: underlying medical disorders.

Mean calcium intake at 26 weeks was; calcium group: 1129 (SD 736) and placebo group 914 (478).


InterventionsCalcium carbonate 1.5 g (500 mg tablets) from 26 weeks' gestation vs placebo tablets. Women at John Hopkins Hospital also received vitamin preparations containing 200 mg calcium and 100 mg magnesium per day.


OutcomesWeight gain in last trimester of pregnancy; BP increase; gestational hypertension.


NotesRecruitment 1983-1985. 34 black women from John Hopkins Hospital, Baltimore, USA, 18 white women from Rosario, Argentina.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate





Villar 1990

MethodsDouble-blind, randomised trial. Allocation by opaque envelopes, ordered by a computer-generated list of random numbers.


ParticipantsPregnant women 17 years or younger; no underlying medical disorders; most were nulliparous with known last menstrual period and singleton pregnancy.


Interventions2 g elemental calcium as 500 mg calcium carbonate tablets, vs placebo tablets. All women were prescribed prenatal vitamin tablets containing 200 mg calcium and 100 mg magnesium per day.


OutcomesPreterm labour; preterm delivery (< 37 weeks); delivery 30-37 weeks; idiopathic prematurity; spontaneous prematurity; low birthweight (< 2500 g); postdates > 42 weeks (calcium 7.4 vs placebo 5.3%); impaired fetal growth (3.2 vs 3.2%); premature rupture of membranes (2.1 vs 1.0%); Apgar score < 8 at 5 minutes (4.4 vs 10.5%).


NotesJohn Hopkins Hospital, Baltimore, 1985-1988.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearD - Not used





WHO 2006

MethodsDouble-blind, randomised trial. Randomisation stratified by centre, with computer generated blocks of 6-8. Allocation by consecutively numbered treatment packs containing calcium tablets or identical placebo. Treatment packs were prepared centrally.


ParticipantsPopulations with median daily calcium intake < 600 mg; Primiparous women less than 20 weeks pregnant. Exclusion criteria: renal disease or urolithiasis; parathyroid disease; blood pressure > 140 mmHg systolic or > 90 mmHg diastolic; history of hypertension; antihypertensive therapy; diuretic, digoxin, phenytoin or tetracycline treatment.


InterventionsChewable calcium carbonate tablets with 500 mg elemental calcium, 3 daily, or identical placebo, from enrolment till delivery.


OutcomesPrimary outcomes: preeclampsia (blood pressure diastolic 90 mmHg or more, or systolic 140 mmHg or more, plus proteinuria 2+ on dipsticks or 300 mg per day; preterm birth (< 37 weeks). Secondary outcomes: severe pre-eclampsia (diastolic 110 mmHg or more or systolic 160 mmHg or more); early onset pre-eclampsia (< 32 weeks), pregnancy induced hypertension; eclampsia; placental abruption; birthweight < 2500 g; spontaneous preterm delivery; medically indicated preterm delivery; admission to neonatal ICU for > 2 days; fetal, neonatal and perinatal mortality (before discharge from hospital).


NotesMulticentre trial in Argentina, Egypt, India, Peru, South Africa and Vietnam.
14,362 women screened, 8325 randomised. Exclusions: 6 calcium (4 not pregnant, 2 lost before treatment started) and 7 placebo (5 not pregnant, 2 lost before treatment started). Loss to follow up: 143 and 155 in calcium and placebo group respectively (some data available on women not followed up to delivery). Treatment compliance 84.5% and 86.2% respectively. Baseline characteristics well matched.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

 BP: blood pressure
CI: confidence interval
DBP: diastolic blood pressure
RR: relative risk
SBP: systolic blood pressure
SD: standard deviation
SEM: standard error of the mean
vs: versus


 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Almirante 1998The method of allocation is not clear from the abstract.

August 2002Excluded pending full report of results. Inadequate data in abstracts for inclusion.

Belizan 1983N = 36. No clinically important outcomes presented in format suitable for inclusion in this review.

Participants: healthy, 20-35 years, singleton pregnancy.
Intervention: calcium 1 g (n = 11), calcium 2 g (n = 11) or placebo (n = 14).
Outcomes: DBP 20-24 weeks, and in the third trimester.
Study design: randomised, no further information.

Boggess 1997N = 23. After randomisation, 5/23 (22%) were excluded.

Participants: 18-35 years. Excluded if BP > 140/90 mmHg at 24 weeks; smokers; illicit drug use; multiple pregnancy; cardiovascular renal or endocrine disease; hypertension in previous pregnancy; calcium supplementation > 200-250 mg elemental calcium.
Intervention: oral calcium carbonate 1.5 g/day for 6 weeks from 28-31 weeks, or placebo tablets. All had 200-250 mg calcium in standard prenatal vitamin-mineral preparations.
Outcomes: gestational hypertension (BP at least 140.90 mmHg on 2 occasions, 6 hours apart); pre-eclampsia (gestational hypertension plus at least 1+ proteinuria)
Study design: randomised trial. Randomisation schedule in balanced blocks of 10.

Chames 2002Excluded pending publication of full report. No relevant clinical outcomes reported in the abstract. No difference found in blood lead levels between women receiving calcium 1000 mg daily from 13-19 weeks (n = 24) or placebo (n = 26).

Cong 1995Beijing Obstetrics and Gynecology Hospital. Three studies reported, but due to serious uncertainty about the method of randomisation in these studies, all have been excluded from this review.

Study 1: calcium 120 mg vs 480 mg vs no calcium.
Study 2: calcium 1 g vs 2 g vs no calcium.
Study 3: calcium 2 g vs no calcium.

Felix 1991Excluded as allocation was by alternation, not random. 14 women received calcium supplementation and 11 received placebo. No women developed hypertension or pre-eclampsia. The production of 6-keto-prostaglandin F1alpha by umbilical arteries was similar between groups.

Herrera 1998Excluded because the intervention was a combination of calcium and linoleic acid.

Kawasaki 1985N = 94. Not a randomised trial.

Interventions: calcium L-aspartate 600 mg/day from 20 weeks to delivery (n = 22) vs no supplementation (n = 72).
Outcomes: pregnancy-induced hypertension.

Knight 1992Excluded because no clinically relevant outcomes reported, placebo not used, and participants not followed till delivery. Normotensive (n = 30 and hypertensive (BP 140/85 mmHg or more, n = 20) nulliparous women "randomly allocated" to receive calcium 1 gram from about 12 weeks to 32 weeks, or a control group. Follow up continued to 36 weeks. Mean diastolic blood pressure reduced in the hypertensive group receiving calcium.

Lavin 1986Planned trial of calcium versus placebo in women with a positive roll-over test at 28-32 weeks. Trial apparently cancelled.

Marya 1987N = 400. The method for allocating women to the two groups was not clear from the report. Additional information obtained from the first author indicated that alternate allocation was used.

Interventions: calcium 375 mg per day plus vitamin D 1200 IU per day from 20-24 weeks onward, and no supplementation.
Outcomes: 'toxaemia'.

Montanaro 1990N = 170. No placebo.

Participants: normotensive at 24 weeks' pregnancy.
Interventions: calcium 2 g/day from 24 weeks to delivery.
Outcomes: pregnancy induced hypertension, pre-eclampsia.
Study design: "randomised, single-blinded trial".

Prada 2001Excluded pending publication of full report. Abstract does not include outcomes specified for this review. Mean blood pressure was reduced in adolescents receiving calcium supplementation 1000 mg daily (n = 62) compared with placebo (n = 62). Not clear whether participants in this report include participants from Prada 2002.

Prada 2002Excluded pending publication of full report. Abstract does not include outcomes specified for this review. Mean blood pressure was similar in adolescents and women with twin pregnancy receiving calcium supplementation 1000 mg daily (n = 94) compared with placebo (n = 93). Not clear whether participants in this report include participants from Prada 2001.

Raman 1978N = 273. Allocation was by strict rotation, a quasi-randomised trial. Supplementation with < 1 g/day.

Repke 1989N = 255. Presented as abstract only. No clinical data available.

Interventions: calcium 2 g/day vs placebo, after 20 weeks of pregnancy.
Study design: 'randomised clinical trial'.

Rogers 1999Excluded because: (1) randomisation performed "using five unsealed envelopes"; unequal group numbers suggested that 'something went wrong with the randomisation process'; (2) no placebo used; (3) initial calcium dose 600 mg per day (1200 mg per day after 32 weeks); (4) 10% loss to follow up.

Hypertension alone occurred in 21/144 women who received calcium compared with 18/75 controls; pre-eclampsia in 8/144 vs 7/75 respectively.

S-Ramos 1995N = 75. Excluded because calcium used for treatment of women with pre-eclampsia rather than prevention.

Participants: nulliparous, gestation 24-36 weeks; mild pre-eclampsia (BP 140/90-160/100, proteinuria at least 300 mg/day).
Interventions: calcium 2 g/day elemental calcium (four tablets of calcium carbonate 1250 mg), versus matching placebo.
Outcomes: initial and last BP and biochemical markers; preterm delivery; caesarean section; severe pre-eclampsia; gestation at delivery; birthweight; Apgar < 7 at 1 minute and 5 minutes; cord arterial pH < 7.16; fetal growth restriction; perinatal death.
Study design: double-blind, placebo-controlled study using a computer-generated random number list.

Suzuki 1996N = 152. Not a randomised trial.

Interventions: calcium 1 g/day from 20 weeks vs no calcium.
Outcomes: pre-eclampsia, gestational hypertension.

Taherian 2002Inclusion citeria not met: not placebo-controlled, calcium dose < 1 g. Three-way comparison between calcium 500 mg, low-dose aspirin and no treatment. Pre-eclampsia diagnosed in 13/330, 15/330 and 33/330 respectively.

Tamas 1997Study of treatment of gestational hypertension, not prevention, using the drug dobesilate calcium, not calcium supplementation.

Wanchu 2001No placebo used. 120 consecutive nulliparous women less than 20 weeks pregnant "randomly assigned" to receive 2 g elemental calcium daily, or no treatment. Analysis restricted to 100 women who "completed the protocol". Mild pre-eclampsia occurred in 9/50 vs 6/50 and severe pre-eclampsia in 0/50 vs 2/50 study vs control groups respectively.

 BP: blood pressure
DBP: diastolic blood pressure
IU: international unit
vs: versus


 
Characteristics of ongoing studies [ordered by study ID]
Mahomed 1998

Trial name or titleCalcium supplementation for the prevention of pregnancy induced hypertension and preterm labour in twin pregnancies: a randomised controlled trial.

Methods

ParticipantsWomen with twin pregnancy.

InterventionsCalcium solution (1 g elemental calcium per 5 ml).

OutcomesPregnancy-induced hypertension, preterm labour, perinatal mortality and short-term morbidity, maternal morbidity.

Starting dateNot stated.

Contact informationProf K Mahomed.

NotesSample size 400 per group.



 
Comparison 1. Routine calcium supplementation in pregnancy by baseline dietary calcium

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 High blood pressure (with or without proteinuria)1114946Risk Ratio (M-H, Random, 95% CI)0.70 [0.57, 0.86]

    1.1 Adequate calcium diet
45022Risk Ratio (M-H, Random, 95% CI)0.90 [0.81, 0.99]

    1.2 Low calcium diet
69894Risk Ratio (M-H, Random, 95% CI)0.47 [0.29, 0.76]

    1.3 Dietary calcium not specified
130Risk Ratio (M-H, Random, 95% CI)0.91 [0.57, 1.45]

 2 Pre-eclampsia1215206Risk Ratio (M-H, Random, 95% CI)0.48 [0.33, 0.69]

    2.1 Adequate calcium diet
45022Risk Ratio (M-H, Random, 95% CI)0.62 [0.32, 1.20]

    2.2 Low calcium diet
710154Risk Ratio (M-H, Random, 95% CI)0.36 [0.18, 0.70]

    2.3 Dietary calcium not specified
130Risk Ratio (M-H, Random, 95% CI)0.14 [0.02, 1.02]

 3 Maternal death/serious morbidity49732Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.65, 0.97]

   3.1 Adequate calcium diet
00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

    3.3 Low calcium diet
49732Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.65, 0.97]

 4 Placental abruption514309Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.55, 1.34]

    4.1 Adequate calcium diet
34830Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.39, 1.68]

    4.3 Low calcium diet
29479Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.51, 1.56]

 5 Caesarean section714710Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.88, 1.01]

    5.1 Adequate calcium diet
34981Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.84, 1.07]

    5.3 Low calcium diet
49729Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.87, 1.03]

 6 Proteinuria (gestational with no proteinuria18312Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.86, 1.26]

   6.1 Adequate calcium diet
00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

    6.2 Low calcium diet
18312Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.86, 1.26]

 7 Severe pre-eclamsia18302Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.48, 1.15]

   7.1 Adequate calcium diet
00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

    7.2 Low calcium diet
18302Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.48, 1.15]

 8 Eclampsia212901Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.41, 1.27]

    8.1 Adequate calcium diet
14589Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.25, 3.99]

    8.2 Low calcium diet
18312Risk Ratio (M-H, Fixed, 95% CI)0.68 [0.37, 1.26]

 9 HELLP syndrome212901Risk Ratio (M-H, Fixed, 95% CI)2.67 [1.05, 6.82]

    9.1 Adequate calcium diet
14589Risk Ratio (M-H, Fixed, 95% CI)3.50 [0.73, 16.82]

    9.2 Low calcium diet
18312Risk Ratio (M-H, Fixed, 95% CI)2.26 [0.70, 7.32]

 10 ICU admission18312Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.66, 1.07]

   10.1 Adequate calcium diet
00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

    10.2 Low calcium diet
18312Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.66, 1.07]

 11 Maternal death18312Risk Ratio (M-H, Fixed, 95% CI)0.17 [0.02, 1.39]

   11.1 Adequate calcium diet
00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

    11.2 Low calcium diet
18312Risk Ratio (M-H, Fixed, 95% CI)0.17 [0.02, 1.39]

 13 Preterm birth1014751Risk Ratio (M-H, Random, 95% CI)0.81 [0.64, 1.03]

    13.1 Adequate calcium diet
45033Risk Ratio (M-H, Random, 95% CI)0.59 [0.26, 1.33]

    13.3 Low calcium diet
69718Risk Ratio (M-H, Random, 95% CI)0.90 [0.80, 1.02]

 14 Birthweight < 2500 g814359Risk Ratio (M-H, Random, 95% CI)0.84 [0.68, 1.03]

    14.1 Adequate calcium diet
45033Risk Ratio (M-H, Random, 95% CI)0.59 [0.31, 1.13]

    14.3 Low calcium diet
49326Risk Ratio (M-H, Random, 95% CI)0.97 [0.86, 1.08]

 15 Neonate small-for-gestational age as defined by trial authors313091Risk Ratio (M-H, Fixed, 95% CI)1.10 [0.88, 1.37]

    15.1 Adequate calcium diet
14589Risk Ratio (M-H, Fixed, 95% CI)1.18 [0.92, 1.52]

    15.3 Low calcium diet
28502Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.59, 1.38]

 16 Admission to neonatal intensive care unit413406Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.94, 1.18]

    16.1 Adequate calcium diet
14336Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.95, 1.26]

    16.3 Low calcium diet
39070Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.81, 1.19]

 18 Stillbirth or death before discharge from hospital1015141Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.73, 1.09]

    18.1 Adequate calcium diet
45033Risk Ratio (M-H, Fixed, 95% CI)1.12 [0.66, 1.90]

    18.3 Low calcium diet
610108Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.69, 1.06]

 21 Childhood systolic blood pressure > 95th percentile1514Risk Ratio (M-H, Fixed, 95% CI)0.59 [0.39, 0.91]

   21.1 Adequate calcium diet
00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

    21.3 Low calcium diet
1514Risk Ratio (M-H, Fixed, 95% CI)0.59 [0.39, 0.91]

 22 Childhood diastolic blood pressure > 95th percentile1514Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.50, 1.31]

   22.1 Adequate calcium diet
00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

    22.3 Low calcium diet
1514Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.50, 1.31]

 
Comparison 2. Routine calcium supplementation in pregnancy by hypertension risk

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 High blood pressure (with or without proteinuria)1114946Risk Ratio (M-H, Random, 95% CI)0.70 [0.57, 0.86]

    1.1 Low-risk women
714619Risk Ratio (M-H, Random, 95% CI)0.78 [0.64, 0.95]

    1.2 High-risk women
4327Risk Ratio (M-H, Random, 95% CI)0.47 [0.22, 0.97]

 2 Pre-eclampsia1215206Risk Ratio (M-H, Random, 95% CI)0.48 [0.33, 0.69]

    2.1 Low-risk women
714619Risk Ratio (M-H, Random, 95% CI)0.68 [0.49, 0.94]

    2.2 High-risk women
5587Risk Ratio (M-H, Random, 95% CI)0.22 [0.12, 0.42]

 13 Preterm birth1014751Risk Ratio (M-H, Random, 95% CI)0.81 [0.64, 1.03]

    13.1 Low-risk women
614183Risk Ratio (M-H, Random, 95% CI)0.91 [0.74, 1.12]

    13.2 High-risk women
4568Risk Ratio (M-H, Random, 95% CI)0.45 [0.24, 0.83]

 16 Admission to neonatal intensive care unit413406Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.94, 1.18]

    16.1 Low-risk women
313343Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.94, 1.19]

    16.2 High-risk women
163Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.03, 2.48]

 18 Stillbirth or death before discharge from hospital1015141Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.73, 1.09]

    18.1 Low-risk women
714629Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.73, 1.09]

    18.2 High-risk women
3512Risk Ratio (M-H, Fixed, 95% CI)0.39 [0.02, 9.20]

 
Comparison 3. Routine calcium supplementation in pregnancy by study sample size

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 High blood pressure (with or without proteinuria)1114946Risk Ratio (M-H, Random, 95% CI)0.70 [0.57, 0.86]

    1.1 Studies with < 400 participants
7675Risk Ratio (M-H, Random, 95% CI)0.38 [0.21, 0.68]

    1.2 Studies with =/> 400 participants
414271Risk Ratio (M-H, Random, 95% CI)0.90 [0.81, 1.00]

 2 Pre-eclampsia1215206Risk Ratio (M-H, Random, 95% CI)0.48 [0.33, 0.69]

    2.1 Studies with < 400 participants
8935Risk Ratio (M-H, Random, 95% CI)0.21 [0.12, 0.36]

    2.2 Studies with =/> 400 participants
414271Risk Ratio (M-H, Random, 95% CI)0.85 [0.69, 1.05]

 13 Preterm birth1014751Risk Ratio (M-H, Random, 95% CI)0.81 [0.64, 1.03]

    13.1 Studies with < 400 participants
6810Risk Ratio (M-H, Random, 95% CI)0.43 [0.24, 0.76]

    13.2 Studies with =/> 400 participants
413941Risk Ratio (M-H, Random, 95% CI)0.93 [0.76, 1.13]

 16 Admission to neonatal intensive care unit413406Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.94, 1.18]

    16.1 Studies with < 400 participants
163Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.03, 2.48]

    16.2 Studies with =/> 400 participants
313343Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.94, 1.19]

 18 Stillbirth or death before discharge from hospital1015141Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.73, 1.09]

    18.1 Studies with < 400 participants
6846Risk Ratio (M-H, Fixed, 95% CI)0.39 [0.02, 9.20]

    18.2 Studies with =/> 400 participants
414295Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.73, 1.09]

 
Comparison 4. Routine calcium supplementation in pregnancy by baseline dietary calcium and study sample size

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 2 Pre-eclampsia1215206Risk Ratio (M-H, Random, 95% CI)0.48 [0.33, 0.69]

    2.1 Adequate calcium/small study
2230Risk Ratio (M-H, Random, 95% CI)0.26 [0.04, 1.50]

    2.2 Adequate calcium/large study
24792Risk Ratio (M-H, Random, 95% CI)0.70 [0.33, 1.46]

    2.3 Low calcium/small study
5675Risk Ratio (M-H, Random, 95% CI)0.21 [0.12, 0.38]

    2.4 Low calcium/large study
29479Risk Ratio (M-H, Random, 95% CI)0.89 [0.74, 1.09]

    2.5 Dietary calcium not specified
130Risk Ratio (M-H, Random, 95% CI)0.14 [0.02, 1.02]