Vitamin D and Health

in those born to control mothers and who had been hypocalcaemic compared to those born to
supplemented mothers.
6.182 Brooke et al. (1981) randomly allocated women of South Asian ethnic origin (n=126) to receive vitamin
D 2 (25 µg/1000 IU daily) or placebo in a double-blind design. Five control infants but no treatment
group infants developed symptomatic hypocalcaemia 62 . At delivery, between group differences in
mean maternal plasma 25(OH)D concentration (168 nmol/L, intervention group; 16 nmol/L, control
group) and mean umbilical venous plasma 25(OH)D concentration (138 nmol/L, intervention group;
10 nmol/L, control group) were very striking and have not been replicated in any subsequent studies.
6.183 Delvin et al. (1986) randomly assigned pregnant women (n=40) in the 6 th month of pregnancy to
receive either vitamin D 3 (25 µg/1000 IU daily) or no treatment. There was a significant decrease
(p < 0.002) in serum calcium at 4 days of age in both groups although to a lesser extent in infants born
to the supplemented mothers (p < 0.05).
Birth weight and length, small for gestational age
Systematic reviews
6.184 A Cochrane systematic review of randomised trials (De-Regil et al., 2016) reported no difference in
birth weight of infants born to vitamin D supplemented women compared to those of mothers who
were not supplemented (5 trials; n=715). Four trials (n=638) suggested a trend for higher birth length
(p=0.06) among infants whose mothers had taken vitamin D supplements during pregnancy compared
to no treatment/placebo but there was considerable heterogeneity (I 2 = 77%) and a significantly
higher mean head circumference at birth (mean difference=0.43; 95% CI, 0.03-0.83). Three trials
(n=477) suggested that vitamin D supplemented women had a lower risk of a preterm birth (RR=0.36;
95% CI, 0.14-0.93); however vitamin D plus calcium supplements (3 trials; n=798) during pregnancy
appeared to increase risk of preterm birth (RR=1.57; 95% CI, 1.02-2.43). The authors noted that most
of the trials were of low methodological quality with many studies at high risk of bias for blinding and
attrition rates and advised caution in the interpretation of the findings.
6.185 Another systematic review (Harvey et al., 2014) identified 9 intervention studies (n=40-350); only 1 of
these was double-blinded and placebo controlled (Brooke et al., 1980). Three studies (all from India)
reported birth weight was significantly greater in infants of vitamin D supplemented mothers but the 3
studies from the UK (Brooke et al., 1980; Congdon et al., 1983; Yu et al., 2009) did not. Meta-analysis
of the studies did not find a significant difference in birth weight between supplemented and
unsupplemented groups. Out of 2 RCTs which examined birth length, 1 (Brooke et al., 1980) found no
effect of daily vitamin D 2 supplementation (25 µg/1000 IU) during the last trimester while the other
(Marya et al., 1988) reported significantly higher birth length (p < 0.001) in infants of women
supplemented with vitamin D 3 (15,000 µg/600,000 IU in 7 th and 8 th month of gestation). Two trials
(Brooke et al., 1980; Yu et al., 2009) found no effect of vitamin D supplementation on risk of offspring
being born small for gestational age 63 (SGA).
6.186 The Harvey et al. (2014) review also included 19 observational studies on the association between
maternal serum 25(OH)D concentration and infant birth weight (14 cohort, 5 cross-sectional); 3 out of
14 studies that had measured maternal serum 25(OH)D concentration reported a significant positive
association with infant birth weight. Out of 8 cohort studies, none found an association between
62 Defined as plasma calcium < 1.8 mmol/L)
63 Both trials defined SGA as infants born below the 10 th percentile for birth weight.
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