Table 12. The effect of maternal vitamin D status in gestation on offpring head circumference (HC) – Observational studies.

First Author and year	Bias score	Study details	Study type	Confounders/ adjustments	Number of weeks gestation when 25(OH)D was measured	Mean (SD) or median (IQR) 25(OH) D concentration (nmol/l)	Mean (SD) or median (IQR) HC (cm)					Unadjusted regression co-efficient β (95% CI) for HC (cm) per 1nmol/l increase in 25(OH)D	Adjusted regression co-efficient β (95% CI) for HC (cm) per 1 nmol/l increase in 25(OH)D	Conclusion
Ardawi, 1997 87	5 (low)	Jeddah, Saudi Arabia Cohort size=264 women	Cohort	nil	Delivery	47.71 (15.77) 25(OH)D <20 nmol/l in 23% 25(OH)D >20 nmol/l in 77%			25(OH)D <20 nmol/l (n=24)	25(OH)D >20 nmol/l (n=240)		Not given	Not given	No difference in offspring HC in mothers with 25(OH)D <20 nmol/l at delivery compared to those with 25(OH)D >20nmol/l
							HC (cm)		34.8 (1.3)	34.11 (1.46)
Mannion, 2006 83	1 (med)	Calgary, Canada n=279women, 207 women restricted milk intake (≤250ml milk) which equates to ≤90 IU vitamin D and 72 not restricting milk intake	Cohort	No adjustments made for HC	Not measured directly Repeat 24 hour dietary telephone recall. 3 or 4 times during pregnancy (1 cup of milk = 90 IU vitamin D)	In those not restricting milk, Vitamin D intake= 524 (180)IU/day In those restricting milk, <2.25mcg/day per day, vitamin D intake=316 (188)IU/day	In those not restricting milk, unadjusted HC= 34.6 (1.5) In those restricting milk, unadjusted HC= 34.3 (1.5) P (diff. between groups)=0.19					Not given	Not given	No difference in offspring HC in mothers restricting milk intake in pregnancy compared to those with unrestricted intake
Morley, 2006 91	8 (low)	Melbourne, Australia n=374 women (232 recruited in winter, 127 in summer)	Cohort	Sex, maternal height, whether first child, smoking, season of blood sample	11 weeks and 28-32 weeks	Winter recruitment, geometric mean at 11 wks= 49.2; 26-32 wks=48.3 Summer recruitment geometric mean at 11 weeks= 62.6; 26-32 wks=68.9	HC	25(OH)D <28 (nmol/l) at 28-32 wk	25(OH)D ≥28 (nmol/l) at 28-32 wk	Diff	Adj. Diff	At 28-32 wks β for every Log2 increase in 25(OH)D = −0.02 (−0.2, 0.2)	At 28-32 wks β for every Log2 increase in 25(OH)D = −0.05 (−0.3, 0.2)	No significant association seen between Log 25(OH)D at 11 wks (data not given) or 28-32 wks and offspring HC
								34.5 (1.5)	34.7 (1.5)	−0.2	−0.2
Sabour,2006 88	−2 (high)	Tehran, Iran n=449 women	Cross- sectional	Nil	Not measured directly Estimated from validated dietary FFQ at delivery (unclear when assessed)	Not measured Mean vitamin D intake = 90.4 (74.8) IU/day	Overall group mean (SD)			34.81 (6.55)		Not given	Not given	No significant association seen between maternal vitamin D intake and offspring HC P=0.47
							Vit D intake <200 IU/day			34.51 (2.66))
							Vit D intake >200 IU/day			35.19 (10.38
Magbooli, 2007 89	1 (med)	Tehran, Iran n=552 women	Cross- sectional	None	Delivery*	27.82 (21.71)*	Not given					Not given	Not given	No significant association seen between serum 25(OH)D3 and offspring HC. p not given
Clifton-Bligh, 2008 92	6 (low)	New South Wales, Australia N=307 women (included 81 women with GDM)	Prospective cohort	Gestational age	Mean (SD) 28.7 (3.3) weeks	53.8 (23.9)	Not given					Not given	Not given	No association between maternal 25(OH)D and offspring HC p>0.4
Gale, 2008 25	4 (med)	Princess Anne Cohort, Southampton, UK n=466 women	Cohort	Gestational age, maternal age, maternal BMI, ethnicity and parity	Late pregnancy Median 32.6 weeks (32.0−31.4)	50 (30−75.3) 50.4% had 25(OH)D >50nmol/k 28.3% had levels 27.5−50 nmol/l 21.1% had levels <27.5 nmol/l	Not given					β per Log 25(OH)D increase = 0.06 (−0.14, 0.26) p=0.557	β per Log 25(OH)D increase = 0.06 (−0.13, 0.25) p=0.530	No association seen between maternal serum 25(OH)D and offspring HC
Farrant, 2009 90	5 (low)	Mysore Parthenon Study, India n=559 women (included 34 women with GDM)	cohort	Maternal age, fat mass, diabetes status	30 (+/− 2) weeks	37.8 (24.0−58.5) 60% of women had 25(OH)D <50 nmol/l, 31% below 28 nmol/l	53.40 (1.53)					β per Log 25(OH)D increase= −0.002 (−0.19-0.19) P=0.98	β per Log 25(OH)D increase= −0.01 (−0.41-0.39) P=0.96	No association seen between late pregnancy maternal Log serum 25(OH)D and offspring HC at birth
Prentice, 2009 95	5 (low)	Gambia, Africa Subset of pregnant Gambian women participating in a calcium supplementation trial n=125 women	Cohort	Season, mat height, weight, weight gain, infant sex and whether received calcium supplement	20 weeks and 36 weeks	20 weeks =103 (25) 36 weeks =111 (27)	35.5 (1.6)*					−0.0371 (0.112) p=0.52	−0.0465 (0.113) p=0.42	No significant association seen between maternal 25(OH)D and offspring HC when analysed both continuously and categorically (25(OH)D >80 nmol/l vs <80 nmol/l) Still no association when HC measured again at 13 or 52 weeks
Viljakainen, 2010 94	3 (med)	Helsinki, Finland n=125 women recruited during last trimester (Oct-Dec). All Caucasian, non-smokers, primiparous	Cohort	No adjustments made for HC	First trimester (8−10 weeks) and 2 days post-partum. Mean of 2 values used to calculate “vitamin D status”	At 8-10 weeks = 41.0 (13.6) Postpartum = 45.1 (11.9) Overall median “vitamin D status=” 42.6	HC (cm)		25(OH) below median (42.6 nmol/l)	25 (OH)D above median (42.6 nmol/l)	P (diff. between means)	Not given	Not given	No significant difference in offspring HC if maternal 25(OH) below median compare to above (median=42.6 nmol/l)
									35.7 (1.4)	35.5 (1.6)	0.511
Dror, 2012 93	7 (low)	Oakland California n=120 women	Cross- sectional	Gestational age, maternal age, maternal BMI, maternal height, ethnicity, parity, GDM, infant age in days, infant feeding practice (breast, formula, mixed)	Peri-natal	75.5 (32.3)	Not given*					−0.003 (−0.012, 0.005) p=0.46	0.005 (−0.013, 0.003) p=0.23	No association seen between maternal serum 25(OH)D and offspring HC

^*HC measured in infant at 2 weeks

^**HC measured in infant between 8-21 days old