Table 8. The effect of maternal Vitamin D status in gestation on offspring birth weight (BW) - 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)	Birth weight (g) mean (SD) or median (IQR)					Unadjusted regression co-efficient β (95% CI) for BW (g) per 1nmol/l increase in 25(OH)D	Adjusted regression co-efficient β (95% CI) for BW (g) 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 BW in mothers with 25(OH)D <20 nmol/l at delivery compared to those with 25(OH)D >20 nmol/l
							BW		3323 (439)	3481 (410)
Weiler, 2005 86	3 (med)	Winnipeg, Canada Sample size for analysis=50 women	Cross-section al	Nil, but no significant difference in terms of offspring sex, season of birth, gestational age at birth in mothers with 25(OH)D >37.5 nmol/l compared with those with 25(OH)D <37.5 nmol/l Significant difference in race between the 2 groups (p=0.010)	Within 48 hours of delivery	Overall mean not given Mean in adequate 25(OH)D group (>37.5 nmol/l, n=32)= 61.6 (24.7) Mean in the deficient group (<37.5 nmol/l, n=18)=28.6 (7.8)			25(OH)D <37.5 nmol/l (n=18)	25(OH)D ≥37.5 nmol/l (n=32)		Not given	Not given	Offspring BW in mothers with 25(OH)D ≥37.5 nmol/l significantly lower than in mothers with 25(OH)D <37.5 nmol/l p=0.022
							BW		3698 (380)	3399 (451)
Mannion, 2006 83	1 (med)	Calgary, Canada n=279 women, 207 women restricted milk intake (≤250ml milk) which equates to ≤90 IU vitamin D and 72 did not restrict milk intake	Cohort	Gestational weight gain, maternal age, height, education, BMI put into regression	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, BW=3530 (466) In those restricting milk, BW=3410 (475) p (diff. between groups) =0.07					Not given	Not given β for each 40 IU/day increase in vitamin D intake = 10.97 (1.19, 20.75) p=0.029	Vitamin D intake in pregnancy is positively associated with offspring BW
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	3540 (520)					At 28-32 wks β for every Log2 increase in 25(OH)D = 40 (−39−119)	At 28-32 wks β for every Log2 increase in 25(OH)D = 31 (−51, 112)	No significant association seen between Log 25(OH)D at 11 wks (data not given) or 28-32 wks and offspring birth weight
								25(OH)D <28 nmol/) at 28-32 wk	25(OH) D >28 nmol/l at 28-32 wk	Diff	Adj Diff
							BW	3397 (57)	3555 (52)	−157	−153
Sabour, 2006 88	−2 (high)	Tehran, Iran n=449 women	Cross-section al	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)		3190 (450)			Not given	Not given	No significant association seen between vitamin D intake and birth weight p=0.53
							Vit D intake <200 IU/day		3150 (480)
							Vit D intake >200 IU/day		3190 (440)
Magbooli, 2007 89	1 (med)	Tehran, Iran n=552 women	Cross- sectional	None	Delivery*	27.82 (10.86)*	3190 (225)					Not given	Not given	No significant association seen between serum 25(OH)D3 and birth weight. p not given
Clifton-Bligh, 2008 92	6 (low)	New South Wales, Australia n=307 women (included 81 women with GDM)	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 birth weight p>0.4
Harvey, 2008 64		Southampton Women’s Survey n=604 women	Cohort	Gestational age, maternal age, maternal BMI, parity	34 weeks		3506 (441)					β per Log 25(OH)D increase = 31.59 (−44.19, 107.36) p=0.42	β per Log 25(OH)D increase = 68.27 (−7.16, 143.71) p=0.08	No significant association seen between maternal serum Log 25(OH)D and offspring birth weight
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 (IQR) 32.6 (32-33.4) weeks	50 (30, 75.3) 50.4% had 25(OH)D >50 nmol/l 28.3% had levels 27.5-50 nmol/l 21.1% had levels <27.5 nmol/l	Divided into quartiles according to maternal 25(OH)D (nmol/l) <30: 3380 (460) 30-50: 3400 (560) 50-75: 3490 (570) >75: 3430 (510)					β per Log 25(OH)D increase = 1.45 (−31.4, 21.7) p=0.247	β per Log 25(OH)D increase = 52.9 (−14.4, 120.3) p=0.123	No significant association seen between maternal serum Log 25(OH)D and offspring birth weight
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% had 25(OH)D < 28 nmol/l	Geometric mean (IQR) = 2900 (400)					β per Log 25(OH)D increase= −26.82 (−79.28, 25.65) p=0.32	β per Log 25(OH)D increase= −72.47 (−195.82, 50.88) p=0.25	No association seen between late pregnancy maternal Log serum 25(OH)D and offspring birth weight when data analysed both continuously or dividing the group into categories using 25(OH)D <50nmol/l as a threshold (p=0.8)
Scholl, 2009 84	2 (med)	The Camden Study, New Jersey, USA n=2251 low income minority pregnant women (47% Hispanic, 37% African American, 15% White)	Cohort	Energy intake, calcium, folate, iron, zinc, protein, age, parity, BMI, ethnicity and gestational age	Not measured directly. Estimated from FFQ at 20 and 28 weeks to calculate daily intake during pregnancy	412.4 (3.56) IU/day	3196 (12.77)					Not given	Not given	Positive association seen between vitamin D intake and birthweight p for trend = 0.043 (after adjustments) When comparing birth weight in those with intake of <200 IU /day (inadequate intake) to those >200 IU/day (adequate intake , p=0.0270 (after adjustments)
							Vitamin D intake (IU/day)			BW
							<285			3163(21)
							285-368			3187(20)
							368-440			3193(19)
							440-535			3207(19)
							>535			3228(23)
Amirlak, 2009 80	2(med)	UAE n=84 healthy Arab and South Asian women with uncomplicated term deliveries	Cross- sectional	Cord blood vitamin A, Maternal ferritin	Delivery	18.5(11.0, 25.4)	3317 (510)					Unadjusted β not given Unadjusted r= 0.23; p<0.05	11.6 (3.0-20.1) P=0.009	Positive correlation seen between maternal 25(OH)D at delivery and birthweight. For every 1 unit increase in 25(OH)D, birth weight increased by 11.6 g
Bowyer, 2009 81	4 (med)	Sydney, Australia n=971 women	Cohort	Gestation, maternal age, overseas maternal birth place	30-32 weeks	52.0 (17, 174) Median Vit D concentration according to group: Vit D ≤25 nmol l (n=144)= 18 (17, 22) Vit D 26-50 (n=317) = 39 (32, 45) Vit D >50 (n=510) = 73 (60-91)	25(O H)D nmol/l	Unadjusted birth weight		Adjusted birth weight		Not given	Not given	Offspring birth weight significantly lower in women with 25(OH)D deficiency (≤25 nmol/l) p<0.001
							≤25	3254 (545)		Not given
							>25	3453 (555)		Not given
							Difference (95% CI)	195 (90-305)		151 (50-250)
Prentice, 2009 95	5 (low)	Gambia, Africa Subset of pregnant Gambian women participating in a calcium supplementatio n 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)		2990 (360)				At 36 weeks= −0.70(+/−2.35) P=0.55	At 36 weeks= −0.12 (+/−2.16) p=0.91	No significant association seen between maternal 25(OH)D and offspring birth weight when analysed both continuously and categorically (25(OH)D >80 nmol/l vs <80 nmol/l)
Sayers, 2009 42	3 (med)	Avon Longitudinal Study of Parents and Children (ALSPAC), UK n=13904 women		Nil	Not directly measured Ambient UVB measured during 98 days preceding birth			Boys (n=7192)=3429 (608) Girls (n=6722) =3327 (550)				1.46(−8.14, 11.06) p=0.77		No association between UVB exposure in 3rd trimester and birth weight
Leffelaar, 2010 82	4 (med)	Amsterdam Born Children and their development (ABCD) study cohort=3730 women , all term offspring (37 wks)	Cohort	Gestational age, season of blood sampling, sex, maternal height, maternal age, smoking, pre-pregnancy BMI, educational level, ethnicity, smoking, parity	Early pregnancy (mean 13 weeks)	54.4 (32-78) Group divided by serum vitamin D concentration as follows: >50 nmol/l (median 73.3); 30-49.9 (median 40.4); <29.9 (median 19.9)		Overall=3515.6 (489.1)				1.404 (0.893, 1.916)	0.068 (−0.483, 0.619)	When analysed continuously, no significant relationship observed between maternal early pregnancy 25(OH)D and offspring birth weight. When analysed according to categories of 25(OH)D status, deficient vitamin D status (<29.9 nmol/l) was significantly associated with a lower birth weight. Adjusted —64 (−107.1, −20.9) Insufficient vitamin D (30-49.9 nmol/l)was not significantly associated with birthweight Adjusted β= 1 (−35.1, 37.2) (all β adjusted)
								≤29.9 nmol/l		3418.4 (510.3)
								30-49.9 nmol/l		3505.6 (496.2)
								≥50 nmol/l		3559.8 (471.3)
Watson, 2010 85	3 (med)	Northern New Zealand n=439 women European (75%), Maori (18%) and Pacific Polynesian (7%) women	Cohort	Gestational age, sex, maternal height, weight, smoking, number of pre-schoolers, number of other adults in the house	Not measured directly 24 hour recall and 3 day dietary FFQ at 4 months and 7 months	Mean vitamin D intake at 4 and 7 months = 84 IU/day		3551 (544)				Not given	Not given	Vitamin D intake at 4 months is positively associated with Log (Vitamin D). pP=0.015 No significant association seen at 7 months p value not given
Viljakainen, 2010 94	3 (med)	Helsinki, Finland n=125 women recruited during last trimester (Oct-Dec). All Caucasian, non-smokers, primiparous	Cohort	Parental size, maternal wt gain in pregnancy, solar exposure, total intake of vitamin D and initial 25(OH)D conc.	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 mean=44.8 (11.9) Overall median “vitamin D status” used to categorise group=42.6			25(OH) D 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 birth weight or z-score birth weight if maternal 25(OH)status below median compared to above (median=42.6 nmol/l) A weak inverse correlation was observed with postpartum 25(OH)D and birth weight z-score (r= −0.193, p=0.068). This was further weakened after adjustment for confounders (p=0.07)
								BW (g)	3700 (400)	3520 (440)	0.052
								BW z-score	0.12 (0.81)	−0.23 (1.09)	0.082
Dror, 2012 93	7 (low)	Oakland California n=120 women	Cross- sectional	Gestational age, maternal age, maternal BMI, maternal height, ethnicity, parity, GDM	Peri-natal	75.5 (32.3)		3420 (542)				−0.63 (−3.68−2.43) p=0.69	−1.79 (−4.57−0.98) p=0.20	No association seen between maternal serum 25(OH)D and offspring birth weight

^*Measured 25(OH)D₃