Taking additional vitamin D supplements during pregnancy increases a woman's chances of having a vaginal birth, according to a new study led by the University of Southampton.
Researchers noted that observational studies relating maternal 25-hydroxyvitamin D status to timing and mode of delivery had reported inconsistent results. They, therefore, analysed data from the Maternal Vitamin D Osteoporosis Study (MAVIDOS), a multicentre randomised, double-blind, placebo-controlled trial of vitamin D supplementation in pregnancy whose original aim was to assess the effect of vitamin D on neonatal bone mass.
For their new study, published in the Journal of Public Health, they wanted to assess how vitamin D might influence the incidence of preterm birth (delivery before 37 weeks' completed gestation), delivery mode (categorised as spontaneous vaginal delivery, instrumental delivery including forceps and vacuum extraction, or Caesarean section), and post-partum haemorrhage (PPH, defined as >500 mL estimated blood loss).
Increased Dose of Vitamin D
They followed up 965 women in MAVIDOS who had been randomly allocated to take either an extra 1000 International Units (IU) per day of cholecalciferol from 14 weeks' gestation until delivery, or a matched placebo. The vitamin D dose in the active group was considerably higher than the current NHS recommended dose of 400 IU (10 mcg), but 1000 IU is considered safe by the National Institute for Health and Care Excellence (NICE).
Participants were recruited between 6 October 2008 and 11 February 2014 from three UK hospitals (University Hospital Southampton NHS Foundation Trust, Oxford University Hospitals NHS Foundation Trust, and Sheffield Hospitals NHS Trust) at the time of attendance for early pregnancy ultrasound screening between 11 and 14 weeks' gestation. Women were assessed before starting the study medication and again at 34 weeks' gestation.
All were aged over 18 and had a singleton pregnancy with gestational age less than 17 weeks at the outset, based on LMP and ultrasound measurements. Those already taking vitamin D supplements were excluded, and those with a 25(OH)D level between 25-100 nmol/L and serum calcium under 2.75 mmol/L on a screening blood sample were eligible to enrol. Participants could continue self-administration of dietary supplements containing up to 400 IU/day vitamin D, but women who wished to take higher doses than this were excluded.
Neonatal sex and birth weight, gestational age at birth, mode of delivery, and estimated blood loss were collected by a research nurse/midwife from participants' medical records. Obstetric personnel were not involved in the research and were blinded as to the allocation to cholecalciferol or placebo.
Baseline serum 25(OH)D was similar in the two groups, and by 34 weeks was higher in the vitamin D group, at 68.2 nmol/L (standard deviation [SD] 21.9 nmol/L) compared with 43.4 nmol/L (SD 22.4 nmol/L) in the placebo group. Compliance, measured by remaining pill count at the 34-week assessment, was high in both groups, at 95% or above.
More Vaginal Births and Fewer Instrumental Deliveries
Maternal weight gain during pregnancy, median gestational age at delivery, incidence of preterm birth, neonatal sex ratio, birth weight, and occipitofrontal circumference did not differ significantly between the two groups.
However, analysis revealed that 65.6% of women in the vitamin D group had a spontaneous vaginal delivery, compared with 57.9% in the placebo group. In addition, fewer women from the vitamin D group had an assisted delivery: 13.2% versus 19.4% in the placebo group. The rates of Caesarean section were similar, at 21.3% and 22.7%, respectively. PPH was less common among the women randomised to cholecalciferol (32.1% vs 38.1% in the placebo group), but rates were similar when stratified by delivery mode, reflecting the higher risk of PPH in operative and instrumental deliveries.
The researchers calculated that these figures gave a relative risk (RR) of 1.13 for vaginal delivery in the vitamin D group, with an RR of 0.68 for instrumental delivery. They concluded: "Our findings suggest that antenatal vitamin D supplementation might be effective at reducing the need for an instrumental delivery and as a result the associated risk of PPH."
They added that, as instrumental delivery is also associated with increased risks of perineal trauma, maternal psychological distress, and infant morbidity (such as trauma, jaundice, facial nerve injury, and intracranial haemorrhage), vitamin D supplementation might also reduce these outcomes, although they were not able to assess these directly.
Lead researcher Dr Rebecca Moon, clinical lecturer at the MRC Lifecourse Epidemiology Centre (LEC) at the University of Southampton and NIHR Southampton Biomedical Research Centre, said: "Most women want to have a 'natural delivery' of their baby. Our work suggests that taking extra vitamin D during their pregnancy might help them to achieve this. "The women taking the extra vitamin D also had less blood loss after delivery, highlighting why this is so important. Further evidence is now needed to more thoroughly inform public health policy and clinical practice."
Future studies should additionally aim to establish the benefits of vitamin D supplementation in specific risk groups for both vitamin D deficiency (for example, obesity, prolonged hospital admission or Black, Asian, and Minority Ethnic groups) and adverse obstetric outcomes, the researchers recommended. They suggested also that randomisation be stratified by factors associated with the biochemical response to vitamin D supplementationand risk of poor labour outcomes.
Potential Overall Cost Benefit to NHS
The team also calculated that the number of women needed to treat with 1000 IU/day cholecalciferol to prevent one instrumental delivery was 14. The cost of such supplementation for the duration of pregnancy would be about £15 per woman (at an NHS prescribing cost of £1.45 for 30 tablets), so the cost to prevent one instrumental delivery would be around £210.
Offset against the reduction in maternal and neonatal morbidity, vitamin D supplementation "could be a relatively cheap intervention and warrants further investigation", they said.
If these findings and the other identified benefits of higher dose antenatal vitamin D supplementation, such as increased offspring bone mass, were replicated in further high quality randomised controlled trials without increased risk of harm, "consideration should be given to increasing the recommended pregnancy supplementation guidance to 1000 IU/day in the UK. In the interim, promotion of the current guidelines recommending 400 IU/day vitamin D in pregnancy is appropriate to increase the current low uptake of supplementation".
This work was supported by grants from the Arthritis Research UK, Medical Research Council, Bupa Foundation, National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, and NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. IS and AP were funded by the MRC. The work leading to these results was supported by the European Union’s Seventh Framework Programme, projects EarlyNutrition and ODIN.
