Impact evaluation of the efficacy of different doses of vitamin D supplementation during pregnancy on pregnancy and birth outcomes: a randomised, controlled, dose comparison trial in Pakistan

Sidrah Nausheen, Atif Habib, Maria Bhura, Arjumand Rizvi, Fariha Shaheen, Kehkashan Begum, Junaid Iqbal, Shabina Ariff, Lumaan Shaikh, Syed Shamim Raza, Sajid Bashir Soofi, Sidrah Nausheen, Atif Habib, Maria Bhura, Arjumand Rizvi, Fariha Shaheen, Kehkashan Begum, Junaid Iqbal, Shabina Ariff, Lumaan Shaikh, Syed Shamim Raza, Sajid Bashir Soofi

Abstract

Background: Vitamin D deficiency during pregnancy is a public health problem in Pakistan and is prevalent among most women of reproductive age in the country. Vitamin D supplementation during pregnancy is suggested to prevent adverse pregnancy outcomes and vitamin D deficiency in both the mother and her newborn.

Methods: We conducted a double-blinded, randomised controlled trial in Karachi, Pakistan to evaluate the effect of different doses of vitamin D supplementation during pregnancy on biochemical markers (serum 25(OH)D, calcium, phosphorus and alkaline phosphatase) in women and neonates, and on pregnancy and birth outcomes (gestational diabetes, pre-eclampsia, low birth weight, preterm births and stillbirths).

Results: Pregnant women (N=350) in their first trimester were recruited and randomised to three treatment groups of vitamin D supplementation: 4000 IU/day (group A, n=120), 2000 IU/day (group B, n=115) or 400 IU/day (group C, n=115). Women and their newborn in group A had the lowest vitamin D deficiency at endline (endline: 75.9%; neonatal: 64.9%), followed by group B (endline: 84.9%; neonatal: 73.7%) and then the control group (endline: 90.2%; neonatal: 91.8%). Vitamin D deficiency was significantly lower in group A than in group C (p=0.006) among women at endline and lower in both groups A and B than in the control group (p=0.001) in neonates. Within groups, serum 25(OH)D was significantly higher between baseline and endline in group A and between maternal baseline and neonatal levels in groups A and B. Participant serum 25(OH)D levels at the end of the trial were positively correlated with those in intervention group A (4000 IU/day) (β=4.16, 95% CI 1.6 to 6.7, p=0.002), with food group consumption (β=0.95, 95% CI 0.01 to 1.89, p=0.047) and with baseline levels of serum 25(OH)D (β=0.43, 95% CI 0.29 to 0.58, p<0.0001).

Conclusion: The evidence provided in our study indicates that vitamin D supplementation of 4000 IU/day was more effective in reducing vitamin D deficiency among pregnant women and in improving serum 25(OH)D levels in mothers and their neonates compared with 2000 IU/day and 400 IU/day. Trial registration number NCT02215213.

Keywords: nutrient deficiencies; nutrition assessment; nutritional treatment.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
CONSORT diagram of participant enrolment, allocation, follow-up visits and analysis. CONSORT, Consolidated Standards of Reporting Trials.
Figure 2
Figure 2
Average and 95% CI of serum concentrations of vitamin D in women (baseline and endline) and their newborns across intervention groups. Different letters indicate significant differences between groups among the same population type. Maternal endline: groups A and C were statistically significant (p=0.003). Neonatal: groups A (p

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