1. Objectives

To assess the effects of vitamin B6 supplementation during pregnancy and/or labour on maternal and infant outcomes

2. How studies were identified

The following databases were searched in March 2015:

• Cochrane Pregnancy and Childbirth Group’s Trials Register
• CENTRAL (The Cochrane Library 2015)
• MEDLINE
• Embase
• CINAHL

Reference lists, relevant conference proceedings and journals were also hand-searched

3. Criteria for including studies in the review

3.1 Study type

Randomized controlled trials

3.2 Study participants

Pregnant women, during the prenatal period or during labour

(Studies exclusively evaluating the effect of vitamin B6 on maternal nausea and vomiting were excluded, as this is the subject of a separate Cochrane review)

3.3 Interventions

Supplementation with pyridoxine (vitamin B6), alone or with other micronutrients, compared to placebo or no supplementation, or to the same micronutrients without pyridoxine

3.4 Primary outcomes

Maternal outcomes

• Preeclampsia
• Preterm birth (<37 weeks’ gestation)

Neonatal outcomes

• Low birth weight (<2500 g)

Secondary outcomes for the mother included eclampsia, dental decay, breast milk production, and adverse events, such as sensory neuropathy and seizures. Secondary outcomes for the neonate included mean birth weight, mean birth length, low Apgar score (<7) at one minute or five minutes, cardiovascular malformations, orofacial clefts, long-term developmental delay, adverse events such as seizure, and admission to a neonatal intensive care unit

4. Main results

4.1 Included studies

Four randomized controlled trials, enrolling 1646 women, were included in this review

• In one trial women were recruited during labour, one trial recruited women ≤3.5 months’ gestation, one trial recruited women <5.5 months’ gestation, and one trial recruited women of any gestational age
• Three of the four trials excluded women with any complications of pregnancy at recruitment
• One trial administered 100 mg of pyridoxine hydrochloricum or placebo intramuscularly or orally in the delivery room to 36 women; one trial including 1532 women had three arms: i) multivitamin plus three placebo lozenges daily, ii) multivitamin containing 20 mg pyridoxine plus three placebo lozenges daily, and iii) multivitamin plus three pyridoxine lozenges (6.67 mg each) daily; one trial provided one of seven different amounts of pyridoxine to 45 participants (0 mg to 20 mg/day); and one trial provided either 25 mg pyridoxine hydrochloride or placebo to 33 women

4.2 Study settings

• Hungary and the United States of America (3 trials)
• All trials were published between 1960 and 1984
• Women were recruited in the delivery room or at antenatal clinics; one antenatal clinic was for low-income women
• In one trial baseline intakes of vitamin B6 were evaluated: 83% of participants failed to achieve recommended intakes for pregnancy

4.3 Study settings

How the data were analysed
One comparison was made: pyridoxine versus control. The trial in which pyridoxine was administered during labour was analysed separately from the other three trials. Fixed effects meta-analysis was used to produce summary estimates. For dichotomous data, risk ratios (RR) with corresponding 95% confidence intervals (CI) were produced, and for continuous data, mean differences (MD) and 95% CI were generated. No sensitivity analyses were performed due to insufficient data. Analyses were undertaken as follows:

• Oral tablet supplementation versus control
• Lozenge supplementation versus control
• Intramuscular administration versus control

Results
Pyridoxine versus control
Preeclampsia
Antenatal pyridoxine had no statistically significant effect on the risk of preeclampsia versus control, whether given as oral supplements (RR 1.71, 95% CI [0.85 to 3.45], 2 trials/1197 women) or as lozenges (RR 1.43, 95% CI [0.64 to 3.22], 1 trial/944 women). No other primary outcomes were reported on in the included trials.

Additional outcomes
No eclampsia events occurred in either pyridoxine or control groups in the three trials measuring this outcome. A statistically significant decrease in the risk of maternal dental decay occurred with antenatal oral supplementation (RR 0.84, 95% CI [0.71 to 0.98], p=0.028; 1 trial/371 women) and with antenatal lozenges (RR 0.68, 95% CI [0.56 to 0.83], p=0.0001; 1 trial/342 women). Breast milk production was measured in the supplementation during labour trial, in which no effect of either oral (MD -2.30 g/kg/day, 95% CI [-16.46 to 11.86], 24 women) or intramuscular pyridoxine (MD -6.20, 95% CI [-21.99 to 9.59], 24 women) was found. Antenatal oral pyridoxine supplementation significantly decreased the mean birth weight of infants by -0.23 kg on average (95% CI [-0.42 to -0.02 kg]) in one trial involving 33 women. Low Apgar score at one minute was measured in three trials, of which only one reported any events, finding no statistically significant difference between treatment and control groups (RR 1.85, 95% CI [0.11 to 31.00], 45 women). Low Apgar score at five minutes was measured in the supplementation during labour trial, in which no events occurred. In one trial involving 33 women, no events of clinically significant neuropathy occurred.

5. Additional author observations*

Few trials were identified, and these were judged to be of low methodological quality overall. The trials were conducted prior to recognition of the association between vitamin B6 and neonatal outcomes such as orofacial clefts and cardiovascular malformations, and thus these important outcomes were not assessed. Using the GRADE approach, evidence for the outcomes preeclampsia and dental decay was rated as low quality.

Although antenatal oral pyridoxine supplementation was found to decrease the risk of maternal dental decay, current evidence does not support the use of pyridoxine supplementation in pregnancy. While antenatal oral pyridoxine was found to decrease mean birth weight, this finding was in a single small trial of 33 women.

Further high-quality trials are needed to assess the effect of vitamin B6 on outcomes such as cardiovascular malformations, orofacial clefts, long-term neurological development in the infant, preterm birth, preeclampsia and adverse events.