Should all pregnant women take calcium supplements in Nepal? GRADE evidence to policy assessment

Figures & data

Table 1. Summary of judgements reached under each category of EtD framework.

Title description	Judgement
Problem	No	Probably no	Probably yes	Yes		Varies	Don’t know
Desirable effects	Trivial	Small	Moderate	Large		Varies	Don’t know
Undesirable effects	Large	Moderate	Small	Trivial		Varies	Don’t know
Certainty of evidence	Very low	Low	Moderate	High			No included studies
Values	Important uncertainty or variability	Possibly important uncertainty or variability	Probably no important uncertainty or variability	No important uncertainty or variability
Balance of effects	Favours the comparison	Probably favours the comparison	Does not favour either the intervention or the comparison	Probably favours the intervention	Favours the intervention	Varies	Don’t know
Resources required	Large costs	Moderate costs	Negligible costs and savings	Moderate savings	Large savings	Varies	Don’t know
Certainty of evidence of required resources	Very low	Low	Moderate	High			No included studies
Cost-effectiveness	Favours the comparison	Probably Favours the comparison	Does not favour either the intervention or the comparison	Probably favours the intervention	Favours the intervention	Varies	No included studies
Equity	Reduced	Probably reduced	Probably no impact	Probably increased	Increased	Varies	Don’t know
Acceptability	No	Probably no	Probably yes	Yes		Varies	Don’t know
Feasibility	No	Probably no	Probably yes	Yes		Varies	Don’t know

Judgement for each category is indicated in bold text.

Table 2. GRADE summary of findings tables based on Cochrane systematic review [2].

Certainty assessment							No. of patients		Effect		Quality of the evidence [22]	Importance
No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	High-dose calcium supplementation (>1 g/day)	No calcium supplementation	Relative (95% CI)	Absolute(95% CI)
High-dose calcium supplementation (>1 g/day) compared to no calcium supplementation for preventing pre-eclampsia in pregnancy
Pre-eclampsia (all women)
13	Randomised trials	Not serious	Serious^a	Not serious	Not serious	Publication bias strongly suspected^b	379/7851 (4.8%)	510/7879 (6.5%)	RR 0.45 (0.31–0.65)	36 fewer per 1,000 (from 45 fewer to 23 fewer)	⊕⊕○○ Low	Critical
Pre-eclampsia (women at high risk of pre-eclampsia)
5	Randomised trials	Serious^c	Not serious	Not serious	Not serious	None	9/281 (3.2%)	54/306 (17.6%)	RR 0.22 (0.12–0.42)	138 fewer per 1,000 (from 155 fewer to 102 fewer)	⊕⊕⊕○ Moderate	Critical
Pre-eclampsia (low-calcium diet)
8	Randomised trials	Not serious	Serious^d	Not serious	Not serious	Publication bias strongly suspected^e	209/5331 (3.9%)	306/5347 (5.7%)	RR 0.36 (0.20–0.65)	37 fewer per 1,000 (from 46 fewer to 20 fewer)	⊕⊕○○ Low	Critical
HELLP syndrome
2	Randomised trials	Not serious	Not serious	Not serious	Not serious	None	16/6446 (0.2%)	6/6455 (0.1%)	RR 2.67 (1.05–6.82)	2 more per 1,000 (from 0 fewer to 5 more)	⊕⊕⊕⊕ High	Critical
Low-dose calcium supplementation (<1 g/day) compared to no calcium supplementation for preventing pre-eclampsia in pregnancy
Pre-eclampsia
4	Randomised trials	Very serious^f	Not serious	Not serious	Not serious	None	24/552 (4.3%)	57/428 (13.3%)	RR 0.36 (0.23–0.57)	85 fewer per 1,000 (from 103 fewer to 57 fewer)	⊕⊕○○ Low	Critical
High-dose vs. low-dose calcium supplementation (<1 g/day) compared to no calcium supplementation for preventing pre-eclampsia in pregnancy
Pre-eclampsia
1	Randomised trial	Serious^g	Not serious	oNot serious	Serious^h	None	7/123 (5.7%)	19/139 (13.7%)	RR 0.42 (0.18–0.96)	79 fewer per 1,000 (from 5 fewer to 112 fewer)	⊕⊕○○ Low	Critical

CI, confidence interval; RR, risk ratio; HELLP. haemolysis, elevated liver enzymes and low platelets.

^aSerious heterogeneity (I squared = 70%).

^bSmall study effects.

^cUnclear risk of bias for all the seven domains of bias considered and was published as a letter to the editor (Lopez-Jaramillo et al., 1990).

^dSerious heterogeneity (I squared = 76%).

^eSmall study effects.

^fSerious design limitations.

^gDowngraded by one due to study design limitation.

^hDowngraded by one due to small study size.

Table 3. Potential public health impact in Nepal.

Outcome	Explanation	Illustrative comparative risks^a (95% CI)		Relative risk (95% CI)	Absolute (95% CI)
		Assumed risk	Corresponding risk
		Control	Calcium
Pre- eclampsia	Applying pooled effect estimate from 2018 systematic review to 2009 health facility Emergency-Obstetrics Care-based prevalence in Nepal	7 per 1,000^b	3 per 1,000 (2–5)	0.45 (0.31–0.65)	4 fewer per 1,000 (from 5 fewer to 2 fewer)
	Applying high-risk based pooled effect estimate from 2018 systematic review to 2009 health facility Emergency-Obstetrics Care-based prevalence in Nepal (high-dose calcium)	7 per 1,000	3 per 1,000 (2–4)	0.22 (0.12–0.42)	5 fewer per 1,000 from 6 fewer to 4 fewer)
	Applying low-calcium diet-based pooled effect estimate from 2018 systematic review to 2009 health facility Emergency-Obstetrics Care-based prevalence in Nepal (high-dose calcium)	7 per 1,000	3 per 1,000 (1–5)	0.36 (0.20–0.65)	4 fewer per 1,000 (from 6 fewer to 2 fewer)
	Applying low-dose calcium-based pooled effect estimate from 2018 systematic review to 2009 health facility Emergency-Obstetrics Care-based prevalence in Nepal (below WHO-recommended dose of calcium)	7 per 1,000	3 per 1,000 (2–4)	0.36 (0.23– 0.57)	4 fewer per 1,000 (from 5 fewer to 3 fewer)
	Applying high-dose vs low-dose calcium-based pooled effect estimate from 2018 systematic review to 2009 health facility Emergency-Obstetrics Care-based prevalence in Nepal	7 per 1,000	3 per 1,000 (1–7)	0.42 (0.18–0.96)	4 fewer per 1,000 (from 6 fewer to 0 fewer)
HELLP syndrome	Applying pooled effect estimate from 2018 systematic review to 2009 health facility Emergency-Obstetrics Care-based prevalence in Nepal	7 per 1,000	19 per 1,000 (7–48)	2.67 (1.05–6.82)	12 more per 1,000 (from 0 fewer to 41 more)

^aWe applied effect estimates from the systematic review to a health facility with Emergency-Obstetrics Care-based prevalence of pre-eclampsia in Nepal.

The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

^bBased on 2009 prevalence of pre-eclampsia in Nepal.

Table 4. Cost estimate for blanket supplementation.

	High dose (2 g)	High dose (1.5 g)	Below WHO-recommended dose (1 g) pilot tested in Dailekh	Remarks
Elemental calcium (tablets)	4 tablets of 500 mg each	3 tablets of 500 mg each	2 tablets of 500 mg each
Calcium carbonate required (weight of supplement)	5,000 mg	3,750 mg	2,500 mg	To fulfil the dose of 500 mg of elemental calcium, 1,250 mg of calcium carbonate is required.
Price per dose (Nepalese rupees, NPR) Curex Pharmaceuticals Nepal (0.016 USD/tablet or NPR 1.35/tablet)	5.4	4.05	2.7	NPR 1.35 per 500 mg. Price of calcium tablets likely to be high when the current inflation rate of (6%) is considered.
Duration of intake (days)	225	225	225	Assuming the timing of supplement initiation at 4 months of pregnancy till the postpartum period
Cost per pregnancy (NPR)	5.4 × 225 = 1215	4.05 × 225 = 911	2.7 × 225 = 608
Expected pregnancies (N) [16]	758,652	758,652	758,652	If calcium is to be supplemented to all pregnant women (blanket supplementation)
The total cost of calcium (USD) (approx.)	8 million	6 million	4 million	Cost for calcium supplies only
Logistics costs	High	Moderate	Low	Including storage and transportation cost
Staff training and staff time cost	Staff training for appropriate counselling on calcium supplementation during antenatal care services

Hofmeyr GJ, Lawrie TA, ÁN A, et al. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2018;10. doi:10.1002/14651858.CD001059.pub5

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Departement of Health Services. Ministry of Health and Population Nepal. Annual Report 2075/76 (2018/19). Available from: https://dohs.gov.np/wp-content/uploads/2019/07/DoHS-Annual-Report-FY-2074-75-date-22-Ashad-2076-for-web-1.pdf

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