Pre-Eclampsia, Vitamin D Deficiency
Conditions
Keywords
Maternal vitamin D, Deficiency, Insufficiency, Pregnancy, Pre-eclampsia, IUGR
Brief summary
Vitamin D deficient pregnant ladies were selected and randomized into 2 groups for routine daily dose of multivitamin (400IU vitamin D3) versus maximum safest treatment daily dose (4000IU vitamin D3). Participants were assessed and compared for number of pre-eclampsia cases.
Detailed description
Vitamin D3 has key role in decidualization and implantation of placenta.Vitamin D deficiency is thought to have positive association with pre-eclampsia.Vitamin D deficiency is highly prevalent in some parts of the world and it is not universally screened antenatally. Pre-eclampsia is a known multifactorial pregnancy disorder with significant maternal and perinatal morbidity and mortality. Vitamin D3 has a down-regulating effect on inflammatory pathways and reducing endothelial cell damage. Investigators want to assess in vitamin D deficient group whether treatment reduces the risk of pre-eclampsia.
Interventions
Antenatal multivitamin
4000 IU Vitamin D3 (cholecalciferol) daily = 40 drops daily
Sponsors
King Fahad Medical City
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Confirmed singleton pregnancy of less than 13 completed weeks of gestation at the time of consent. * Planned to receive antenatal care in King Fahad Medical City antenatal clinic. * The ability to provide written informed consent at the first visit. * Low risk pregnancy; and Serum vitamin D3 levels less than \< 25nmol/L.
Exclusion criteria
* Mothers with pregnancy with abnormal foetus. * Previous history of hypertension, pre-eclampsia, recurrent miscarriages. * Chronic kidney disease, chronic liver disease, and malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pre-eclampsia in Both Arms | From 20 weeks of pregnancy till event of pre-eclampsia seen, whichever came first, assessed up to 32 weeks. | Occurrence of pre-eclampsia or not in all patients irrespective of Vitamin D dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vitamin D Level | At 36th week of pregnancy | Level of Improvement in Vitamin D status in both arms |
| Number of Patients With Intrauterine Growth Retardation | At delivery | Patients having fetus with retardation of growth in both arms. |
Participant flow
Pre-assignment details
416 participants were screened. 192 did not meet eligibility criteria. 38 refused to participate and 7 turned out to be ectopic pregnancy.
Participants by arm
| Arm | Count |
|---|---|
| 400 IU Vitamin D3 400IU vitamin D3 contained in antenatal multivitamin once daily by mouth starting from 14 weeks of pregnancy till delivery.
400 IU Vitamin D3: Antenatal multivitamin | 86 |
| 4000 IU Vitamin D3 4000 IU Vitamin D3 drops once daily by mouth starting from 14 weeks of pregnancy till delivery.
4000 IU Vitamin D3: 4000 IU Vitamin D3 (cholecalciferol) daily = 40 drops daily | 93 |
| Total | 179 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Miscarriage | 3 | 6 |
Baseline characteristics
| Characteristic | Total | 400 IU Vitamin D3 | 4000 IU Vitamin D3 |
|---|---|---|---|
| Age, Continuous | 29.3 years STANDARD_DEVIATION 5.2 | 29.3 years STANDARD_DEVIATION 5.3 | 29.4 years STANDARD_DEVIATION 4.8 |
| Body Mass Index (BMI) | 28.4 Kg/m2 STANDARD_DEVIATION 7.2 | 28.8 Kg/m2 STANDARD_DEVIATION 7.3 | 28.1 Kg/m2 STANDARD_DEVIATION 7.2 |
| Primiparity | 64 Participants | 31 Participants | 33 Participants |
| Region of Enrollment Africa | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment India | 8 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Philippines | 10 Participants | 3 Participants | 7 Participants |
| Region of Enrollment Saudi Arabia | 160 Participants | 80 Participants | 80 Participants |
| Sex: Female, Male Female | 179 Participants | 86 Participants | 93 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 86 | 0 / 93 |
| serious Total, serious adverse events | 0 / 86 | 0 / 93 |
Outcome results
Primary
Number of Participants With Pre-eclampsia in Both Arms
Occurrence of pre-eclampsia or not in all patients irrespective of Vitamin D dose.
Time frame: From 20 weeks of pregnancy till event of pre-eclampsia seen, whichever came first, assessed up to 32 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 400 IU | Number of Participants With Pre-eclampsia in Both Arms | 6 Participants |
| 4000 IU | Number of Participants With Pre-eclampsia in Both Arms | 1 Participants |
Comparison: Eligible and consented study subjects were randomized according to permuted block design scheme to be allocated in 400 IU arm and 4000 IU arm.p-value: <0.0595% CI: [0.02, 1.32]Chi-squared
Secondary
Change in Vitamin D Level
Level of Improvement in Vitamin D status in both arms
Time frame: At 36th week of pregnancy
Population: Out of 86 participants randomized for the arm of 400 IU, 3 had miscarriage and 2 lost to follow. So 81 participants were analyzed.~Out of 93 participants randomized for the arm of 4000 IU, 6 had miscarriage and 4 lost to follow. So 83 were analyzed in that arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 400 IU | Change in Vitamin D Level | 35.3 nmol/L | Standard Deviation 20.7 |
| 4000 IU | Change in Vitamin D Level | 72.3 nmol/L | Standard Deviation 30.9 |
p-value: <0.0001t-test, 2 sided
Secondary
Number of Patients With Intrauterine Growth Retardation
Patients having fetus with retardation of growth in both arms.
Time frame: At delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 400 IU | Number of Patients With Intrauterine Growth Retardation | 18 Participants |
| 4000 IU | Number of Patients With Intrauterine Growth Retardation | 8 Participants |
p-value: <0.0295% CI: [0.19, 0.94]Chi-squared