Characteristics of studies.
Characteristics of included studies
| Brooke 1980 | ||
|---|---|---|
| Methods | Randomised double-blind controlled trial; 2-arm design with individual randomisation. | |
| Participants | 126 pregnant women 28–32 weeks of gestation attending the antenatal clinic at St George's Hospital, London, United Kingdom (latitude: 51°30'N, north of tropic of Cancer). All pregnant women were first-generation immigrants mostly from India, Pakistan, Bangladesh, Sri Lanka, Mauritius and east Africa. Exclusion and elimination criteria: preterm deliveries, congenital malformations and maternal illnesses likely to affect fetal growth (such as diabetes). Pre-gestational body mass index and skin pigmentation not reported. |
|
| Interventions | Participants were randomly allocated to 1 of the following groups. Group 1 (n = 59 at the end of the trial): women received daily 1000 IU/day of calciferol (estimated total dose: 56000–84000 IU). Group 2 (n = 67 at the end of the trial): women received a placebo. Start of supplementation: weeks 28–32 gestation. Length of the intervention/follow-up: 8–12 weeks from supplementation to term. Season: authors report that to avoid distortion of the results due to seasonal variation in sunlight hours the trial was carried out during autumn and winter 1977, the whole of 1978 and spring and summer 1979. |
|
| Outcomes |
Maternal: maternal weight gain, dietary vitamin D intake, 25-hydroxy vitamin D (25-OHD) concentrations in cord blood and at term. Plasma calcium (adjusted for albumin concentration), inorganic phosphate, bilirubin, albumin concentrations and total alkaline phosphatase activity, alanine transaminase and y-glutamyl transferase activities, vitamin D binding globulin concentration, compliance. Infant: weight, crown-heel length, crown-rump length, rump-heel length, occipitofrontal head circumference, forearm length, lower leg length, triceps and subscapular skinfold thickness, fontanelle area, plasma cholecalciferol at day 3 and day 6. Weight, length and head circumference at 3,6,9 and 12 months. |
|
| Notes | There were no significant baseline differences between the groups in maternal age, parity, height, vegetarian: non-vegetarian ratio or the distribution of the various countries of origin. | |
| Bias | Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Trial reported random allocation to the groups, although the method of sequence generation was not described. |
| Allocation concealment (selection bias) | Unclear risk | Method of concealment not described. |
| Blinding (performance bias and detection bias) | Low risk | Trial reported as double blind. |
| Incomplete outcome data (attrition bias) | High risk | Unclear number of randomised participants. Preterm deliveries, congenital malformations, and maternal illnesses likely to affect fetal growth (such as diabetes) were eliminated from the trial. There is not complete documentation of the exclusions. |
| Selective reporting (reporting bias) | Unclear risk | There is insufficient information to permit judgement. |
| Other bias | Low risk | The study appears to be free of other sources of bias. |
| Delvin 1986 | ||
|---|---|---|
| Methods | Randomised trial; 2-arm design with individual randomisation. | |
| Participants | 40 pregnant women attending their compulsory visit during the third month of pregnancy at the Obstetrical Unit of the Hopital Edouard Herriot, Lyon, France (latitude: 45° 45' 0" N north of tropic of Cancer). Inclusion criterion: singleton pregnancy at term and uneventful vaginal deliveries. Pre-gestational body mass index and skin pigmentation not reported. | |
| Interventions | Participants were randomly assigned to 1 of the following groups at the time of the compulsory visit. Group 1 (n = 20): women received daily 1000 IU vitamin D3 (estimated total dose: 55000 IU). Group 2 (n = 20): women received no supplement during the last trimester of pregnancy. Start of supplementation: week 27 of gestation (third trimester). Length of the intervention/follow-up: 12 weeks from start of supplementation to term. Season: winter-spring. All selections were performed in December, and all deliveries occurred in June. |
|
| Outcomes |
Maternal: serum (during last trimester of pregnancy) and cord blood immunoreactive parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OHD), 1-alfa,25-dihydroxyvitamin D (1,25(OH)2D), total calcium, ionised calcium, magnesium, inorganic phosphate. Infant: immunoreactive parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OHD), 1-alfa,25-dihydroxyvitamin D (1,25(OH)2D), total calcium, ionised calcium, magnesium, inorganic phosphate at 4 days of age. |
|
| Notes | Compliance was verified weekly visit by a midwife. | |
| Bias | Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Trial reported as randomised but the method of sequence generation was not described. |
| Allocation concealment (selection bias) | Unclear risk | Method of concealment not described. |
| Blinding (performance bias and detection bias) | High risk | Paper describes that participants were allocated to the intervention by a blind randomisation process. Given that the participants did not receive an intervention it is unlikely that the trial was blind. |
| Incomplete outcome data (attrition bias) | High risk | 1 subject from the control group (5%) and 5 (25%) from the vitamin D supplemented group. Laboratory methods reported for 25 to 30 participants (depending on the outcome) out of 40 originally randomised. |
| Selective reporting (reporting bias) | Unclear risk | There is insufficient information to permit judgement. |
| Other bias | Low risk | The study appears to be free of other sources of bias. |
| Mallet 1986 | ||
|---|---|---|
| Methods | Randomised controlled trial; 3-arm design with individual randomisation. | |
| Participants | 77 white pregnant women 18–36 years of age in the last trimester of pregnancy living in Northwest of France (latitude: 49° 26' 0" N north of tropic of Cancer). Pre-gestational body mass index not reported. | |
| Interventions | Participants were randomly assigned to 1 of the following groups. Group 1 (n = 21): women received 1000 IU of vitamin D2 for the last 3 months of pregnancy (estimated total dose throughout pregnancy: 90,000 IU). Group 2 (n = 27): women received a single dose of 200,000 IU (5 mg) vitamin D at the 7th month of pregnancy. Group 3 (n = 29): women received no supplement and served as controls. Start of supplementation: week 28 of gestation (third trimester). Length of the intervention/follow-up: 12 weeks from start of supplementation to term. Season: winter pregnancy. Infants born during February and March. |
|
| Outcomes |
Maternal: 24-hour urinary calcium excretion after 6 week supplementation, calcium, 25-Hydroxyvitamin D (25-OHD) and1-alfa,25-dihydroxyvitamin D (1,25(OH)2D) metabolites of vitamin D from serum and cord during labour and delivery. Infant: serum calcium levels at days 2 and 6 of life, birthweight. |
|
| Notes | ||
| Bias | Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation by random numbers table. |
| Allocation concealment (selection bias) | Unclear Risk | Method of concealment not described. |
| Blinding (performance bias and detection bias) | High risk | Not reported as blinded. Different interventions were used: daily dose or single dose or no supplement. |
| Incomplete outcome data (attrition bias) | High risk | It is unclear if there was attrition, but given the uneven number of participants reported it is likely that there were losses to follow-up. |
| Selective reporting (reporting bias) | Unclear Risk | There is insufficient information to permit judgement. |
| Other bias | High risk | Groups are reported with notorious different sample size. It is unclear whether the numbers reflect the participants who finished the trial (unclear and uneven losses to follow-up); a non randomised process; or a selection bias in which randomised participants did not received the intervention. |
| Marya 1987 | ||
|---|---|---|
| Methods | Randomised controlled trial; 2-arm design with randomisation at individual level. | |
| Participants | 400 pregnant women 20–35 years of age, attending the antenatal clinic of Medical College Hospital in Rohtak, India (latitude: 76° 34' 0' north of Tropic of Cancer). Pre-gestational body mass index and skin pigmentation not reported. | |
| Interventions | Participants were allocated to 1 of the following groups. Group 1 (n = 200) received a daily supplement containing 1200 IU vitamin D and 375 mg calcium (estimated total dose from week 20–24 of gestation to term:134,400–168,000 IU). Group 2 (n = 200) received no supplement from 20–24 weeks of pregnancy until delivery. Start of supplementation: 20–24 weeks pregnancy (third trimester). Length of the intervention/follow-up: 16–20 weeks from start of supplementation to term. Season: not reported. |
|
| Outcomes | Maternal: pre-eclampsia (defined as blood pressure of 140 mmHg or higher systolic and/or 90 mmHg diastolic along with proteinuria higher than 300 mg/24 hours); systolic and diastolic blood pressure at 24, 28, 32 and 36 weeks of gestation. | |
| Notes | Biochemical analysis were made in those who developed pre-eclampsia (n = 12) and also in a group of women with no pre-eclampsia (n = 25) and a control group of non pregnant women. The results of the stratified analysis are not reported in this review. | |
| Bias | Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | '400 pregnant women, of these 200 were randomly selected and put on a daily supplement of calcium and vitamin D. Method of sequence generation not described. |
| Allocation concealment (selection bias) | Unclear risk | Method of concealment not described. |
| Blinding (performance bias and detection bias) | High risk | It is not reported whether the trial was blinded to participants, outcome assessor or care providers. |
| Incomplete outcome data (attrition bias) | High risk | Only data on biochemical were reported for those who developed pre-eclampsia and some of those with no pre-eclampsia and a group of non pregnant controls. |
| Selective reporting (reporting bias) | High risk | Outcomes reported for some subgroups only. |
| Other bias | Low risk | The study appears to be free of other sources of bias. |
| Marya 1988 | ||
|---|---|---|
| Methods | Randomised clinical trial; 2-arm design with individual randomisation. | |
| Participants | 200 pregnant women, aged 22–35 years old, attending the antenatal clinic of the Medical College Hospital, Rohtak, India (latitude: 76° 34' 0' north of Tropic of Cancer). Inclusion criterion: uncomplicated single pregnancy. Exclusion criteria: pre-eclampsia, antepartum haemorrhage, premature delivery. Pre-gestational body mass index and skin pigmentation not reported. | |
| Interventions | Participants were allocated to 1 of the following groups. Group 1 (n = 100): women received 2 doses of 600,000 IU 1 each at 7th and 8th month of pregnancy (estimated total dose: 1200,000 IU). Group 2 (n = 100): women received no intervention. Start of supplementation: 28 weeks pregnancy (third trimester). Length of the intervention/follow-up: 12 weeks from start of supplementation to term. Season: not reported. |
|
| Outcomes |
Maternal: venous and cord serum calcium, serum proteins, inorganic phosphate, alkaline phosphatase, weight. Radiological examination on women with abnormal biochemistry or osteomalacia symptomatology. Side effects: back age, leg-pains, general weakness, cramps. Infant: birthweight, low birthweight, crown-heel length, head circumference, mid-arm circumference within 24 hours after birth. Skinfold thickness (triceps and infrascapular). |
|
| Notes | ||
| Bias | Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | '200 pregnant women, of these 100 were randomly selected (supplemented group) had been administered two doses of vitamin D'. Method of sequence generation not described. |
| Allocation concealment (selection bias) | Unclear risk | Method of concealment not described. |
| Blinding (performance bias and detection bias) | Unclear risk | Method of concealment not described. |
| Blinding (performance bias and detection bias) | High risk | It is not reported whether the trial was blinded to participants, outcome assessor or care providers. |
| Incomplete outcome data (attrition bias) | Unclear risk | Losses to follow-up are not documented although exclusions included pregnancy complications. Result tables mention that each arm was comprised of 100 women, a number that corresponds to that described for the treatment allocation. |
| Selective reporting (reporting bias) | Unclear risk | There is insufficient information to permit judgement. |
| Other bias | Low risk | The study appears to be free of other sources of bias. |
| Yu 2008 | ||
|---|---|---|
| Methods | Randomised controlled trial; 4 × 3 block design with randomisation at individual level. | |
| Participants | 180 pregnant women from the following ethnic populations; 45 Indian Asians, 45 Middle Eastern, 45 Black and 45 Caucasian attending the routine antenatal clinic at St Mary’s Hospital, London, United Kingdom (latitude: 51°30'N north of tropic of Cancer). Exclusion criteria: pre-existing sarcoidosis, osteomalacia, renal dysfunction and tuberculosis. Pre-gestational body mass index and skin pigmentation (in addition to ethnicity) not reported. | |
| Interventions | Women were randomised in blocks of 15 within each of the 4 ethnic groups to 3 groups. Group 1: women received a daily dose of vitamin D (ergocalciferol) at 800 IU (estimated total dose 72,800 IU); Group 2: women received a stat dose of 200,000 IU of calciferol. Group 3: women received no treatment. Start of supplementation: 27 weeks' gestation (third trimester). Length of the intervention/follow-up: 13 weeks from start of supplementation to term. Season: April to November 2007; summer. |
|
| Outcomes | Maternal: Maternal and cord 25-hydroxyvitamin D levels at delivery, maternal PTH and corrected calcium levels at delivery. | |
| Notes | Women who did not speak English were only included if a health advocate was able to interpret and a leaflet was provided in their language. | |
| Bias | Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer-generated random number lists were drawn up by an independent researcher, with randomisation in blocks of 15. |
| Allocation concealment (selection bias) | Low risk | The person seeing the pregnant women allocated the next available number on entry to the trial, and each woman collected her tablets directly from the hospital pharmacy department or her local pharmacy. |
| Blinding (performance bias and detection bias) | High risk | All study personnel and participants were not blinded to treatment assignment. |
| Incomplete outcome data (attrition bias) | Low risk | Only 1 loss to follow-up on group 3. |
| Selective reporting (reporting bias) | Low risk | Unlikely. |
| Other bias | Unclear risk | Women were randomised within each ethnic group. It is not clear if the ethnicity can be clearly established as it was self reported. Women who did not speak English were included only if a health advocate was able to interpret and a leaflet was provided in their language (English, Arabic, Bengali and Farsi) although the ability to read was not clearly established. |
IU: international units