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Intervention Review

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Vitamin D supplementation for women during pregnancy

  1. Luz Maria De-Regil1,*,
  2. Cristina Palacios2,
  3. Ali Ansary3,
  4. Regina Kulier4,
  5. Juan Pablo Peña-Rosas1

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 15 FEB 2012

Assessed as up-to-date: 16 DEC 2011

DOI: 10.1002/14651858.CD008873.pub2


How to Cite

De-Regil LM, Palacios C, Ansary A, Kulier R, Peña-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD008873. DOI: 10.1002/14651858.CD008873.pub2.

Author Information

  1. 1

    World Health Organization, Evidence and Programme Guidance, Department of Nutrition for Health and Development, Geneva, Switzerland

  2. 2

    University of Puerto Rico, Nutrition Program, Department of Human Development, Graduate School of Public Health, San Juan, Puerto Rico

  3. 3

    Children's Hospital of Orange County, Orange, CA, USA

  4. 4

    Geneva, Switzerland

*Luz Maria De-Regil, Evidence and Programme Guidance, Department of Nutrition for Health and Development, World Health Organization, 20 Avenue Appia, Geneva, 1211, Switzerland. deregillu@who.int.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 15 FEB 2012

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Characteristics of included studies [ordered by study ID]
Brooke 1980

MethodsRandomised double-blind controlled trial; 2-arm design with individual randomisation.


Participants126 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.


InterventionsParticipants 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.


OutcomesMaternal: 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.


NotesThere 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.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskTrial reported random allocation to the groups, although the method of sequence generation was not described.

Allocation concealment (selection bias)Unclear riskMethod of concealment not described.

Blinding (performance bias and detection bias)
All outcomes
Low riskTrial reported as double blind.

Incomplete outcome data (attrition bias)
All outcomes
High riskUnclear 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 riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Delvin 1986

MethodsRandomised trial; 2-arm design with individual randomisation.


Participants40 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.


InterventionsParticipants  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.


OutcomesMaternal: 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.


NotesCompliance was verified weekly visit by a midwife.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskTrial reported as randomised but the method of sequence generation was not described.

Allocation concealment (selection bias)Unclear riskMethod of concealment not described.

Blinding (performance bias and detection bias)
All outcomes
High riskPaper 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)
All outcomes
High risk1 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 riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Mallet 1986

MethodsRandomised controlled trial; 3-arm design with individual randomisation.


Participants77 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.


InterventionsParticipants 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.


OutcomesMaternal: 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


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation by random numbers table.

Allocation concealment (selection bias)Unclear riskMethod of concealment not described.

Blinding (performance bias and detection bias)
All outcomes
High riskNot reported as blinded. Different interventions were used: daily dose or single dose or no supplement.

Incomplete outcome data (attrition bias)
All outcomes
High riskIt 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 riskThere is insufficient information to permit judgement.

Other biasHigh riskGroups 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

MethodsRandomised controlled trial; 2-arm design with randomisation at individual level.


Participants400 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.


InterventionsParticipants 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.


OutcomesMaternal: 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.


NotesBiochemical 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.


Risk of bias

BiasAuthors' judgementSupport 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 riskMethod of concealment not described.

Blinding (performance bias and detection bias)
All outcomes
High riskIt is not reported whether the trial was blinded to participants, outcome assessor or care providers.

Incomplete outcome data (attrition bias)
All outcomes
High riskOnly 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 riskOutcomes reported for some subgroups only.

Other biasLow riskThe study appears to be free of other sources of bias.

Marya 1988

MethodsRandomised clinical trial; 2-arm design with individual randomisation.


Participants200 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.


InterventionsParticipants 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.


OutcomesMaternal: 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


Risk of bias

BiasAuthors' judgementSupport 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 riskMethod of concealment not described.

Blinding (performance bias and detection bias)
All outcomes
High riskIt is not reported whether the trial was blinded to participants, outcome assessor or care providers.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLosses 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 riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Yu 2008

MethodsRandomised controlled trial; 4 x 3 block design with randomisation at individual level.


Participants180 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.


InterventionsWomen 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.


OutcomesMaternal: Maternal and cord 25-hydroxyvitamin D levels at delivery, maternal PTH and corrected calcium levels at delivery.


NotesWomen who did not speak English were only included if a health advocate was able to interpret and a leaflet was provided in their language.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random number lists were drawn up by an independent researcher, with randomisation in blocks of 15.

Allocation concealment (selection bias)Low riskThe 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)
All outcomes
High riskAll study personnel and participants were not blinded to treatment assignment.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly 1 loss to follow-up on group 3.

Selective reporting (reporting bias)Low riskUnlikely.

Other biasUnclear riskWomen 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.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Ala-Houhala 198649 healthy, well-nourished mothers delivering in January 1984 in the maternity wards and outpatient clinic of the Department of Paediatrics of the University Central Hospital of Tampere, Finland (latitude 61°N) and exclusively breastfeeding their infants, were divided in succession into 3 groups: group 1 (n = 17): mothers were given 2000 IU vitamin D3 a day, infants not supplemented; group 2 (n = 16): mothers were given 1000 IU vitamin D3 a day, infants not supplemented; group 3 (n = 16): mothers were not supplemented, and their breast fed infants were given 400 IU of vitamin D2 a day. During pregnancy, 33 mothers had no vitamin D supplementation, 8 mothers received 500 IU a day of vitamin D during the second trimester of pregnancy, and 8 mothers received 500 IU a day throughout the pregnancy. The mothers from these 3 groups supplemented in pregnancy were distributed in the postpartum maternal vitamin D supplementation and infant vitamin D supplementation interventions.

This is not a randomised trial and the intervention includes mothers at postpartum and their infants.

Cockburn 19801139 pregnant women were assigned to 1 of 2 wards: group 1 (n = 506) Caucasian pregnant women assigned to 1 ward of the Simpson Memorial Maternity Pavilion, Edinburgh, United Kingdom during the 9 months from September to May, were given a daily dietary supplement of 400 IU of vitamin D2 from about the 12th week of pregnancy until delivery; group 2 women (n = 633) were assigned to another ward over the same period and were given a placebo containing no vitamin D. Outcomes included plasma concentrations of calcium, phosphorus, magnesium, total proteins, and 25-hydroxycholecalciferol at 24th and 34th weeks of pregnancy and at delivery. Infant plasma concentrations of calcium, phosphorus, magnesium, total proteins, and 25-hydroxycholecalciferol were measured from umbilical venous blood taken from the infants at birth and on capillary blood on the 6th day.

This is not a randomised trial.

Das 2009150 consecutive pregnant women pregnant women during their second trimester from 6 villages of a poor socioeconomic region in district Barabanki (latitude 26.8 ºN), Uttar Pradesh, north India.  The participants were initially randomised to receive either no dose or 1 dose of 60,000 IU cholecalciferol under observation in the 5th gestational month. However, the first few results showed rampant vitamin D deficiency and no improvement at delivery despite good exposure to sun and calcium supplementation. Therefore, this randomisation was abandoned subsequently and 2 comparison groups were followed up, alternate women receiving either 60,000 IU in the 5th month or 120,000 IU, each in the 5th and 7th months of pregnancy.

This is not a randomised trial and the comparisons are outside the scope of this review.

Ito 1994876 singleton pregnant women with blood pressure lower than 140/90 mmHg at 20 weeks’ gestation, and no evidence of proteinuria, who were attending the obstetric clinic of Kumamoto University Hospital, Japan were divided into 2 groups: group 1 (n = 666) women received conventional antenatal care; group 2 (n = 210 women) were managed under a protocol for the prediction of pre-eclampsia with an angiotensin sensitivity test and prevention of the condition by calcium supplementation. Participants from group 2 were further assigned to 1 of 4 groups according to their risk of developing pre-eclampsia, based on the angiotensin sensitivity test and the effective pressor dose: group A received 156 mg/day of oral elemental calcium (as calcium L-aspartate, Aspara-Ca from 22 weeks’ gestation, followed by 312 mg/day oral elemental calcium  and vitamin D3 (0.5 μg for 3 days) from 30 weeks’ gestation to term. Participants in group B received 156 mg/day oral elemental calcium from 22 weeks’ gestation and 312 mg/day oral elemental calcium from 30 weeks’ gestation to term; group C received 312 mg/day oral elemental calcium from 30 weeks’ gestation to term and group D received no supplementation.

This is not a randomised trial and the comparisons are outside the scope of this review.

MacDonald 1986This trial was registered in 1986 on the Oxford Database of Perinatal Trials and reports the recruitment and follow-up completed in 1979. The registration form reports a randomised controlled trial to assess the efficacy of calcium and vitamin D supplementation versus placebo in the prevention of maternal and fetal hypocalcaemia. The reports indicates that the sample size was 55 Asian women with morbidity and laboratory results as primary outcomes but no further information is available.

Marya 198145 Hindu pregnant women were randomly assigned to 1 of 2 groups: group 1 (n = 25) received tablets containing 1200 IU vitamin D and 375 mg calcium daily throughout the 3rd trimester; group 2 (n = 20) received oral single dose of 600,000 IU vitamin D2 once during 7th month and 8th month (total 2 doses). This group was compared with group 3 (n = 75) who had not received vitamin D supplements during pregnancy. The results were also compared with data from 25 non pregnant, non-lactating healthy women. Patients with complications such as pre-eclampsia, antepartum haemorrhage or twin pregnancies were excluded.

The randomised study compares 2 doses of vitamin D supplementation. The type of study, type of participants and types of interventions are not eligible for this review.

von Hurst 2009235 South Asian women, aged 23-68 years, living in Auckland, New Zealand were recruited for the study and those who were insulin resistant - homeostasis model assessment 1 (HOMA1) >1.93 and had serum 25-hydroxyvitamin D concentration < 50 nmol/L were randomised to receive 100 μg (4000 IU) vitamin D(3) (n = 42) or placebo (n = 39) daily for 6 months. The study participants were non pregnant women. The type of participants is outside the scope of this review.

Wagner 2006494 apparently healthy pregnant women (16-45 years of age) with 12-16 weeks' gestation of singletons attending prenatal care in Medical University of South Carolina, Charleston, South Carolina in South Carolina, United States were randomised into 1 of 3 groups stratified by race: group 1 received 400 IU vitamin D3/day; group 2 received 2000 IU vitamin D3/day; and group 3 received 4000 IU vitamin D3/day until delivery. All women received daily multiple micronutrients supplements. 350 women continued until delivery. Outcomes included monthly 25-hydroxyvitamin D; 1,25(OH)2D; intact PTH, serum calcium, creatinine, phosphorus, and urinary calcium/creatinine levels, gestational age at delivery, birth weight, mode of delivery, co-morbidities of pregnancy, pre-eclampsia, gestational diabetes, any infection, preterm labour and premature birth.

All women received vitamin D supplementation at different doses. The types of comparison are outside the scope of this review.

 
Characteristics of ongoing studies [ordered by study ID]
Bisgaard 2009

Trial name or titleVitamin D supplementation during pregnancy for prevention of asthma in childhood: an interventional trial in the ABC (Asthma Begins in Childhood) cohort.

MethodsRandomised double-blind, placebo-controlled trial with 2 arms.

ParticipantsDanish-fluent pregnant women 18 years of age or older, with 22-26 week of gestation living in Sealand, Denmark participating in the ABC-cohort. The mothers in ABC also participate in an interventional trial with fish oil supplementation, and the vitamin D randomisation is stratified by fish oil treatment group.

Women with intake of more than 400 IU of vitamin D during the previous 6 months, endocrinological disease such as calcium metabolic disorder, parathyroid disorder, thyroid disorder or Diabetes type 1, tuberculosis, sarcoidosis or in need of diuretics or heart medication including calcium channel blockers are excluded.

InterventionsParticipants are randomised to 1 of 2 groups: group 1 receives a daily supplement with 2400 IU of vitamin D3 from week 24 of gestation to 1 week after delivery ; group 2 receives placebo from week 24 of gestation to 1 week after delivery.

OutcomesPrimary:

Maternal: none.

Infant: recurrent wheeze from 0 to 3 years of age.

Secondary:

Maternal: 25-OH-vitamin D, PTH, Calcium, alkaline phosphatase concentrations 1 week postpartum.

Infant: upper and lower respiratory infections, allergy, eczema from 0-3 years of age.

Starting dateDate of start: 03/2009.

Status: recruiting participants.

Contact informationHans Bisgaard, MD, DMSc

Copenhagen Studies on Asthma in Childhood

Copenhagen University Hospital of Copenhagen

Gentofte, Denmark, 2820

Tel: +45 39777360

E-mail: bisgaard@copsac.com

NotesSponsor: Copenhagen Studies on Asthma in Childhood.

Das 2010

Trial name or titleVitamin D and calcium nutrition in pregnancy-evaluation of optimal supplementation dose of vitamin D during antenatal period.

MethodsRandomised, parallel group, multiple-arm trial.

Participants200 consecutive pregnant women attending antenatal clinic of at Queen Mary Hospital in CSMMU (former KGMC) will be enrolled into the study after taking informed consent. Patients already on calcium or on vitamin D supplementation, on anticonvulsants, on antitubercular treatment or having any medical condition affecting calcium and vitamin D metabolism (e.g. renal or liver disease) will be excluded.

InterventionsParticipants will be randomly assigned to 1 of 3 groups: group 1 will receive 3 single doses of 120,000 IU vitamin D each provided every 8 weeks apart + 500 mg elemental calcium (as calcium carbonate) and 250 IU vitamin D twice a day, daily throughout pregnancy; group 2 will receive 3 single doses of 60,000 IU vitamin D each provided every 8 weeks apart + 500 mg elemental calcium (as calcium carbonate) and 250 IU vitamin D twice a day, daily throughout pregnancy; group 3 will receive 500 mg elemental calcium (as calcium carbonate) and 250 IU vitamin D twice a day daily throughout pregnancy.  

OutcomesPrimary:

Maternal 25-hydroxyvitamin D, calcium and albumin at baseline, 2nd trimester (14-20 weeks' gestation) and at delivery.

Infant: cord blood 25-hydroxyvitamin D and albumin at delivery, neonatal calcium at 4-6 days after delivery. 

Secondary:

Maternal: none.

Infant: newborn's anterior fontanelle diameter, birthweight, crown heel length, head circumference within 24 hours after birth, occurrence of neonatal seizures, other morbidity within 1 week of delivery.

Starting dateDate of start:18-09-2009.

Status: open to recruitment.

Contact informationDr Vinita Das

CSM Medical University

Chowk , Lucknow, Uttar Pradesh, 226003 , India

Tel: +91 522 2257742

Email: fogsiemoc_lko@yahoo.co.in

 

Dr Vijailakshmi Bhatia

SGPGI , Lucknow , Uttar Pradesh, 226014 , India

Tel: +91 522 2494380

Email: bhatiaviji@gmail.com 

NotesFinancial Support: Council of Science & Technology, UP.

Goldring 2010

Trial name or titleEffects of prenatal vitamin D supplementation on respiratory and allergic phenotypes and bone density in the first 3 years of life.

MethodsRandomised interventional prevention trial.

Participants180 mothers attending antenatal clinic at St Marys Hospital, London United Kingdom. This is a follow-up trial of the infants of these trial participants. All of the offspring of the 180 mothers recruited in this trial are eligible and are invited to participate in this follow-up study when their children are 3 years of age.

InterventionsParticipants were randomised at 27 weeks' gestation to 1 of 2 groups: group 1 received no vitamin D (n = 60), group 2: received 800 IU of vitamin D daily for the remainder of pregnancy (n = 60); group 3 (n = 60) received a single oral dose of 200,000 IU vitamin D at 27 weeks' gestation.

OutcomesPrimary:

Maternal: none.

Infant: wheezing episode in the first 3 years of life, measured at 36-48 months.

Secondary:

Maternal: none.

Infant: use of inhaled bronchodilators in the last 12 months, doctor-diagnosed rhinitis, any wheezing episode in the preceding 12 months, doctor-diagnosed asthma, doctor-diagnosed eczema, doctor-diagnosed food allergy, positive skin prick test responses, 25-hydroxyvitamin D levels, bronchodilator responsiveness, exhaled nitric oxide level (in parts per billion), nasal secretions for inflammatory mediators, pulmonary airflow resistance and reactance at a range of frequencies using impulse oscillometry, total number of all wheezing episodes since birth and total number of upper and lower respiratory tract infections since birth, at 36-48 months.

Starting dateDate of start: 01/03/2010.

Status: ongoing. Anticipated end date: 31/05/2011.

Contact informationDr Stephen Goldring

Department of Paediatrics

Wright-Fleming Institute

Norfolk Place, London

W2 1PG , United Kingdom

E-mail: sgoldring@nhs.net

NotesSponsor: Imperial College London (UK).

Grant 2010

Trial name or titleRandomised placebo-controlled study of vitamin D3 during pregnancy and infancy to determine the vitamin D dose in pregnancy and early life that safely and effectively increases serum vitamin D concentration in infants.

MethodsRandomised controlled trial, blinded.

Participants260 pregnant women attending antenatal care and intending to delivery at Middlemore Hospital, in the suburb of Middlemore, Manukau City, New Zealand and who are either public patients attending the antenatal clinics at Middlemore hospital or whose lead maternity caregiver is a member of South Auckland Maternity Care Limited.

Pregnant mothers taking vitamin D supplementation that exceeds 200 IU/day and those with a history of renal stones or hypercalcaemia or found to be hypercalcaemic at enrolment, or with any serious complication of pregnancy at the time of enrolment will be excluded.

Their infants will be further randomised to vitamin D supplementation regimens or placebo from birth to 6 months of age.

InterventionsParticipants will be randomly assigned to 1 of 3 groups: group 1 will receive 1000 IU/day of vitamin D3; group 2 will receive 2000 IU/day of vitamin D3; and group 3 will receive a placebo. Each enrolled pregnant woman will receive the intervention from enrolment at approximately 28 gestation until delivery.

The infants of these mothers will be randomised to receive placebo, if their mother was randomised to placebo, 400 IU/day (if mother’s dose was 1000 IU/day) or 800 IU/day of vitamin D3 (if mother’s dose was 2000 IU/day). Vitamin D supplementation and placebo will be an oral liquid medicine. Each enrolled infant will receive the supplement from birth until 6 months of age.

Vitamin D supplementation and placebo will be an oral liquid medicine (purified components of coconut and palm oil).

OutcomesPrimary:

Maternal:number of mothers hypercalcaemia at any measurement point, serum calcium concentration at 36 week of gestation.

Infant: proportion of infants achieving a serum 25[OH]vitamin D concentration > 75 nmol/L at 6 months of age, serum calcium concentration on an umbilical cord blood sample collected at birth, and on blood samples at 2, 4 and 6 months of age, number of infants with hypercalcaemia at any measurement point. 

Secondary:

Maternal: proportion of mothers achieving a serum 25[OH]vitamin D concentration > 75 nmol/L at 36 weeks' gestation. 

Starting dateDate of start: 1/04/2010.

Status: open to recruitment.

Contact informationAssociate Professor Cameron Grant cc.grant@auckland.ac.nz 64 9 373 7999.

NotesFinancial support:

Australian Research Council, Health Research Council of New Zealand

Level 3, 110 Stanley Street, Auckland, 1010, New Zealand PO Box 5541, WellesleyStreet, Auckland, 1141, New Zealand

Sponsors: University of Auckland, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand and University of Otago, School of Medicine & Health Sciences, University of Otago, Wellington PO Box 7343, Wellington South, Wellington 6242, New Zealand.

Habib 2010

Trial name or titleEvaluation of the effectiveness of vitamin D supplementation to pregnant women and their infants in Pakistan.

MethodsRandomised controlled trial.

Participants550 apparently healthy pregnant women 15-49 years of age from 20-22 weeks of gestation and their infants in Pakistan.

Pregnant women with pre existing type 1 or type II diabetes, multiple fetuses, babies (twins, triplets), with high levels of vitamin D will be excluded. Infants with multiple congenital anomalies, serious birth injury, birth asphyxia, serious infections, very low birthweight, will be excluded.

InterventionsParticipants will be individually randomised to 1 of 2 groups: group 1 will receive a daily dose of 4000 IU of vitamin D from 20-22 weeks of pregnancy till the time of delivery; group 2 will receive placebo.

The infants will be stratified in 2 groups: group 1 will receive 400 IU of vitamin D for 6 months as intervention (if mothers are from group 1); group 2 will receive placebo (if mothers are from group 2).

OutcomesPrimary:

Maternal: pre-eclampsia, gestational hypertension, poor weight gain during pregnancy. Stillbirth rates,

Infant: low birthweight, prematurity, neonatal seizures, infants with growth failure, signs and symptoms of vitamin D deficiency, infections: pneumonia, diarrhoea and receptor polymorphism.

Secondary:

Maternal: prevalence and risk factors for maternal vitamin D deficiency.

Infant: prevalence and risk factors for neonatal vitamin D deficiency.

Starting dateDate of start: February 2010.

Status: recruiting participants. Estimated study completion date: June 2011.

Contact informationMuhammad Atif Habib, MBBS, MPH

Project Office Aga Khan University

Phone: +92 21 3 4864798

Email: atif.habib@aku.edu

Principal investigator: Zulfiqar A Bhutta, FRCPCH, PhD

Aga Khan University, Pakistan.

NotesSponsors: Aga Khan University and John Snow, Inc.

Hacker 2010

Trial name or titleTesting the calcium DRI during pregnancy: a study of bone health in black and white women.

MethodsRandomised controlled trial.

Participants120 African American or Caucasian primigravidae women 19-40 years of age in their first trimester of pregnancy in Children's Hospital & Research Center Oakland, California, USA.

Women who are smokers, have a pre-pregnancy body mass index (BMI) higher than 30, have a medical condition that affects bone or taking a medication that affects bone will be excluded.

InterventionsParticipants will be randomly assigned to 1 of 3 groups: group 1 will receive 1000 mg of calcium; group 2 will receive 2000 IU vitamin D and group 3 will receive a placebo. The intervention will be provided from week 16 of pregnancy until delivery.

OutcomesPrimary:

Maternal: change in peripheral cortical and trabecular bone loss and gain during a reproductive cycle in black and white women.

Infant: none.

Secondary: change in bone markers of bone formation and resorption during pregnancy and postpartum, differences in calcium absorption in late pregnancy among black and white women, differences in adaptive immune function tests and markers of inflammation during pregnancy.

Infant: none.

Starting dateDate of start: 05/2010.

Status: currently recruiting participants.

Expected study completion date: May 2013.

Contact informationAndrea N Hacker, MS, RD

Children's Hospital & ResearchCenter Oakland, CA, USA

Phone: +1 510 428-3885

Email: efung@mail.cho.org

Principal Investigators: Ellen Fung, PhD, RD and Janet King, PhD, RD

NotesSponsors: Children's Hospital & Research Center Oakland and USDA, Western Human Nutrition Research Center, USA.

Judkins 2011

Trial name or titleA randomised double-blinded interventional trial to determine the effect of 50,000 IU vitamin D supplementation monthly or twice monthly from 20 weeks' gestation.

MethodsRandomised double-masked clinical trial with randomisation at the individual level. Method of sequence generation: serial tossing of a coin. Allocation will be not concealed.

ParticipantsPregnant women seeking maternity care with midwifery services involved in the study. Exclusion criteria: antenatal Vitamin D level is > 75 nmol/L when enrolling in study

InterventionsThere are two arms in the study. One arm of the study will receive 50,000 IU tablets twice monthly, 2 weeks apart. The other arm of the study will receive 50,000 IU monthly and a placebo monthly, 2 weeks apart from 20 weeks' gestation until delivery of baby. The placebo tablet contains lactose monohydrate, acacia, calcium carbonate, castor oil, maize starch, povidone, sucrose, purified talc, hydrated silica, powdered cellulose, magnesium sterate, shellac, gelatin, beeswax white, titanium dioxide and prepared theobroma.

OutcomesAt delivery. Vitamin D levels taken from the cord blood samples at delivery. If emergencies at delivery prevent a cord blood sample being taken then a maternal venous blood sample will be taken for analysis.

Starting dateStatus: not yet recruiting participants.

Contact informationDr Annie Judkins

Newtown Union Health Service
14 Hall Ave

Newtown
Wellington
6021

New Zealand

annie.judkins@nuhs.org.nz

NotesACTR Number: ACTRN12610001044011

Rasmussen 2009

Trial name or titleEffects of vitamin D supplement before and during and after pregnancy on complications, birthweight and bone mineral density during lactation.

MethodsDouble-blind, randomised, placebo-controlled trial.

Participants400 apparently healthy women 30-35 years of age, all with concentrations of P-25-hydroxyvitamin D (25OHD)- lower than 50 nmol/L. All women included attempts to get pregnant. Visits take place at Clinic of Osteoporosis, Department of Endocrinology, at Aarhus University Hospital, Aarhus, Denmark.

Women with infertility, an intake of 400 IU or more vitamin D/day, cancer, history of alcohol or drug abuse, calcium metabolic disturbances or spontaneous abortion within last 6 months will be excluded.

InterventionsParticipants will be randomly assigned to 1 of 3 groups: group 1 will receive 35 µg per day cholecalciferol; group 2 will receive 70 µg per day cholecalciferol; and group 3 will receive placebo. All women will receive 2 tablets daily from baseline until 16 weeks after delivery.

Intervention with cholecalciferol or placebo starts before pregnancy is achieved and continues until 4 months after the women has given birth.  

OutcomesPrimary:

Infant: birthweight.

Maternal: none

Secondary:

Infant: weight, crown-heel length and head circumference, and infections within 16 weeks after birth. Concentration of 25OHD in umbilical cord and venous sample 16 weeks after birth.

Maternal: postpartum effects of vitamin D supplement on maternal bone mineral density, concentration of 25OHD in mothers milk, incidence of pre-eclampsia and abortions.

Starting dateDate of start: 12/2009.

Status: recruiting participants.

Estimated study completion date: December 2011.

Contact informationGitte Bloch Rasmussen, MD

Department of Endocrinology

Aarhus University Hospital

University of Aarhus

Phone: +45 89 4976 81

Email: gittebr@ki.au.dk

NotesSponsor: University of Aarhus, Denmark.

Roth 2010

Trial name or titleThe effect of antenatal vitamin D supplementation on maternal-fetal vitamin D status and neonatal immune function: a randomised controlled trial in Bangladesh.

MethodsRandomised, placebo controlled trial.

Participants160 pregnant women aged 18-34 years of age with 26-29 weeks of gestation living in Dhaka planning a delivery at the Shimantik maternity centre, Dhaka, Bangladesh and planning to live in this location for at least 1 month postpartum.

Women who use any dietary supplement containing more than 400 IU/day (10 mcg/day) of vitamin D within the month prior to enrolment, or refusal to stop taking supplemental vitamin D at any dose after enrolment; currently use of anti-convulsant or anti-mycobacterial (tuberculosis) medications; have severe anaemia (haemoglobin concentration less than 70 g/L); have a complicated medical or obstetric history that may increase the risk of preterm birth or labour/delivery complications; or a prior history of delivery of an infant with a major congenital anomaly, birth asphyxia, or perinatal death (stillbirth or death within first week of life) will be excluded.

InterventionsParticipants will be randomly assigned to 1 of 2 groups: group 1 will receive a weekly dose of 35,000 IU vitamin D3 (875 μg/week); group 2 will receive placebo (Miglyol® 812). Intervention will start in the third trimester at 26-29 weeks' gestation until delivery.

OutcomesPrimary:

Maternal: serum 25-hydroxyvitamin D concentration during third trimester.

Infant: neonatal serum 25-hydroxyvitamin D concentration (cord blood).

Secondary:

Maternal: serum calcium concentration, urine Ca:Cr ration during third trimester.

Infant: neonatal immune function (cord blood) measured as in vitro stimulated cord blood mononuclear cell (CBMC) LL-37 expression, gene expression related to inflammatory and immunoregulatory pathways, Th1/Th2 cytokine secretion, and bactericidal properties.

Starting dateDate of start: 06/2010.

Status: ongoing.

Estimated study completion date: May 2011.

Contact informationDaniel Roth, MD

Johns Hopkins Bloomberg School of Public Health, USA.

Email: droth@jhsph.edu

Principal Investigators: Dr Abdullah Baqui, Dr Daniel Roth, Dr Rubhana Raqib.

NotesSponsors: Johns Hopkins Bloomberg School of Public Health and International Centre for Diarrhoeal Disease Research, Bangladesh.

Soheilykhah 2011

Trial name or titleEffect of different doses of vitamin D on insulin resistance in pregnant women attending in Shahid Sadoughi and Mojibian prenatal clinics

MethodsRandomised clinical trial with randomisation at the individual level.

Participants150 pregnant women with gestational age less than 12 weeks without gestational diabetes, history of PCO, BMI less than 27kg/m2 before pregnancy, no Vit D supplementation in the past 6 months. Exclusion criteria: diabetes or gestational diabetes treated with insulin, thyroid or parathyroid disorders, hypertension, PCO.

InterventionsWomen will be randomly allocated to:

Intervention group 1: Vit D supplementation, 2000 IU, daily for 6 months

Intervention group 2: Vit D supplementation, 4000 IU, daily for 6 months

Control group: vit D, 200 IU (conventional dose), daily for 6 months

OutcomesGestational Diabetes, insulin concentration, vitamin D concentration.

Starting dateIrct registration number : IRCT138811203312N1
Status: recruiting

Contact informationDr. Sedigheh Soheilykhah

Shahid Sadoughi hospital, Yazd,

Islamic Republic of Iran

8917965556
00983518224001
s_soheilykhah@ssu.ac.ir

NotesFunding source: Yazd Diabetes ResearchCenter, Shahid Sadoughi University of Medical Sciences

Irct registration number : IRCT138811203312N1

 
Comparison 1. Vitamin D alone versus no treatment/placebo (no vitamins or minerals)

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

1 Pre-eclampsia (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

2 Gestational diabetes (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 3 Maternal vitamin D levels at term (25-hydroxyvitamin D) (nmol/L) (ALL)4414Mean Difference (IV, Random, 95% CI)47.08 [23.76, 70.39]

 4 Maternal vitamin D levels at term (25-hydroxyvitamin D) (nmol/L) by supplementation scheme/regimen4502Mean Difference (IV, Random, 95% CI)31.35 [19.03, 43.66]

    4.1 Single dose
2175Mean Difference (IV, Random, 95% CI)12.19 [2.82, 21.57]

    4.2 Daily
4327Mean Difference (IV, Random, 95% CI)49.70 [21.86, 77.54]

   4.3 Weekly
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 5 Maternal vitamin D levels at term (25-hydroxyvitamin D) (nmol/L) by total dose4414Mean Difference (IV, Random, 95% CI)47.08 [23.76, 70.39]

    5.1 56,000 IU or less
132Mean Difference (IV, Random, 95% CI)32.45 [19.48, 45.42]

    5.2 56,000 IU to 200,000 IU
3382Mean Difference (IV, Random, 95% CI)52.86 [24.07, 81.66]

   5.3 More than 200,000 IU
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 6 Maternal vitamin D levels at term (25-hydroxyvitamin D) (nmol/L) by season at the start of pregnancy4414Mean Difference (IV, Random, 95% CI)47.08 [23.76, 70.39]

    6.1 Summer
1179Mean Difference (IV, Random, 95% CI)11.0 [5.03, 16.97]

    6.2 Winter
2109Mean Difference (IV, Random, 95% CI)23.08 [7.46, 38.69]

    6.3 Unknown
1126Mean Difference (IV, Random, 95% CI)151.8 [126.74, 176.86]

7 Preterm birth (less than 37 weeks' gestation) (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 8 Low birthweight (less than 2500 g) (ALL)3463Risk Ratio (M-H, Random, 95% CI)0.48 [0.23, 1.01]

9 Impaired glucose tolerance00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

10 Caesarean section00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

11 Gestational hypertension00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 12 Side effects (nephritic syndrome) (ALL)1135Risk Ratio (M-H, Random, 95% CI)0.17 [0.01, 4.06]

13 Maternal death (death while pregnant or within 42 days of termination of pregnancy) (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 14 Birth length (cm) (ALL)2326Mean Difference (IV, Random, 95% CI)0.97 [-0.41, 2.34]

 15 Head circumference at birth (cm) (ALL)2326Mean Difference (IV, Random, 95% CI)0.43 [0.06, 0.79]

 16 Birthweight (g) (ALL)3403Mean Difference (IV, Random, 95% CI)39.55 [-240.68, 319.78]

17 Admission to intensive care unit during the neonatal period (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 18 Stillbirth (ALL)1135Risk Ratio (M-H, Random, 95% CI)0.17 [0.01, 4.06]

 19 Neonatal death (ALL)1135Risk Ratio (M-H, Random, 95% CI)0.17 [0.01, 4.06]

20 Apgar score less than seven at five minutes00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

21 Neonatal infection00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

22 Very preterm birth00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Vitamin D + calcium versus no treatment/placebo (no vitamin or minerals)

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

 1 Pre-eclampsia (ALL)1400Risk Ratio (M-H, Random, 95% CI)0.67 [0.33, 1.35]

2 Gestational diabetes (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

3 Preterm birth (less than 37 weeks' gestation) (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

4 Low birthweight (less than 2500 g) (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

5 Maternal vitamin D levels at term (25-hydroxyvitamin D) (nmol/L) (ALL)00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

6 Impaired glucose tolerance00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

7 Caesarean section00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

8 Gestational hypertension00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

9 Side effects (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

10 Maternal death (death while pregnant or within 42 days of termination of pregnancy)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

11 Birth length (cm) (ALL)00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

12 Head circumference at birth (cm) (ALL)00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

13 Birthweight (g) (ALL)00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

14 Admission to intensive care unit during the neonatal period00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

15 Stillbirth (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

16 Neonatal death (ALL)00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

17 Apgar score less than seven at five minutes00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

18 Neonatal infection00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

19 Very preterm birth00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 
Summary of findings for the main comparison. Vitamin D alone versus no treatment/placebo (no vitamins or minerals)

Patient or population: pregnant women
Settings: all settings
Intervention: supplementation with vitamin D alone
Comparison: placebo/no intervention (no vitamins or minerals)

OutcomesRelative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)

Pre-eclampsiaNot estimable0

(0 studies)
No trial assessed this outcome

Gestational diabetesNot estimable0

(0 studies)
No trial assessed this outcome

Maternal vitamin D status at term (25-hydroxyvitamin D in nmol/L)MD 47.08

(23.76, 70.39)
414

(4 studies)
⊕⊕⊝⊝

low 1,2,3

Preterm birthNot estimable0

(0 studies)
No trial assessed this outcome

Low birthweight0.48

(0.23 to 1.01)
463

(3 studies)
⊕⊕⊝⊝

low 1,2,3

CI: confidence interval; RR: risk ratio;

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Two of the included trials have high risk of performance and detection bias as they were not blinded. All trials had unclear allocation concealment.
2 High statistical heterogeneity but consistency in the direction of the effect.

3 Wide confidence intervals.

 
Summary of findings 2. Vitamin D + calcium versus no treatment/placebo (no vitamin or minerals)

Patient or population: pregnant women
Settings: all settings
Intervention: supplementation with vitamin D + calcium
Comparison: placebo/no intervention (no vitamins or minerals)

OutcomesRelative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)

Pre-eclampsia0.67 (0.33, 1.35)400 (1 study)⊕⊝⊝⊝

very low 1,2

Gestational diabetesNot estimable0 (0 studies)No trial assessed this outcome

Maternal vitamin D status at term (25-hydroxyvitamin D in nmol/L)Not estimable0 (0 studies)No trial assessed this outcome

Preterm birthNot estimable0 (0 studies)No trial assessed this outcome

Low birthweightNot estimable0 (0 studies)No trial assessed this outcome

CI: confidence interval; RR: risk ratio;

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1Wide confidence interval.
2 Only one study reported on this outcome. It is unclear how the random sequence was generated and it lacks of blinding. The study is also at high risk of selective reporting as the biochemical indicators were reported only for some groups.