Table 21. The effect of maternal vitamin D status in gestation on preterm birth of the offspring – Observational studies.

First Author and year	Bias score	Study details	Study type	Confounders/ adjustments	Number of weeks gestation when 25(OH)D was measured	Maternal mean (SD) 25(OH)D concentration (nmol/l) in cases of infants born preterm		Maternal mean (SD) 25(OH)D concentration (nmol/l) in full-term infants		Odds ratio (95% CI) of offspring being preterm from univariate analysis		Odds ratio (95% CI) of offspring being preterm from multivariate analysis		Conclusion
Delmas, 1987 117	-4 (high)	Lyon, France. n=9 women (controls) n=10 women (cases of preterm)* None of the women were taking supplemental vitamin D	Case-control	None	Delivery	44.9 (17.5)		47.4 (7.5)		Not given		Not given		No difference in maternal 25(OH)D at delivery in preterm compared to full-term births p value not given
Mehta, 2009 118	2 (med)	Tanzania Overall Cohort=1078 women Women all HIV infected taking part in a clinical trial of vitamin use Cases of preterm** birth=204 Cases of severe preterm*** birth=70 Cohort for analysis=758	Prospective cohort	Multivitamin supplementation, maternal age at baseline, CD4 count at baseline, HIV disease stage at baseline	12-27 weeks (at enrolment to trial)	Mean not given 34% of preterm, 37% of severe preterm had 25(OH)D <80 nmol/l 66% of preterm, 63% of severe preterm had 25(OH) D>80 nmol/l		Not given		RR if maternal 25(OH)D <80 nmol/l compared to >80 nmol/l Preterm= 0.83 (0.65, 1.07) p=0.14 Severe preterm=0.77 (0.49, 1.19) p=0.24		Adjusted RR if maternal 25(OH)D <80 nmol/l compared to >80 nmol/ Preterm= 0.84 (0.65, 1.07). p=0.15 Severe preterm=0.77 (0.50, 1.18). p=0.23		No increased risk of preterm or severe preterm birth if maternal 25(OH)D <80nmol/l compared with > 80nmol/l
Baker, 2011 119	5 (low)	North Carolina, USA Overall cohort size= 4225 women Cases of preterm birth #=40 Controls=120	Nested case-control	Controls matched by race ethnicity in a 3:1 ratio No significant difference in terms of maternal age, ethnicity, parity, private insurance, BMI, gestational age at delivery between cases and controls. Season of blood draw did differ but not significantly (p=0.06) Results adjusted for maternal age, insurance status, BMI, gestational age at serum collection, season of blood draw	11-14 weeks	25(OH)D (nmol/l)	n (%)	25(OH)D (nmol/l)	n (%)	25(OH)D (nmol/l)	OR (95% CI) p value	25 (OH)D (nmol/l)	Adj OR (95% CI) p value	No significant association seen between maternal 25(OH)D and risk of preterm birth
						<50	3 (7.5)	<50	8 (6.7)	<50	1.14 (0.31, 4.26) p=0.61	<50	0.82 (0.19, 3.57) p=0.79
						50-74.9	8 (20)	50-74.9	24 (20)	50-74.9	1.01 (0.42, 2.46) p=0.99	50-74.9	0.87 (0.34, 2.25) p=0.77
						≥75	29 (72.5)	≥75	88 (73.3)	≥75	1 (Ref)	≥75	1 (Ref)
Shand, 2010 114	6 (low)	Vancouver, Canada All women had either clinical or biochemical risk factors for preeclampsia△ Cohort=221 women Cases of preterm birth**=18	Cohort	Maternal age, ethnicity, parity, BMI, season, multivitamin use, smoking	Between 10 and 20 weeks 6 days (mean 18.7 (1.88) weeks)	Not given		Not given		Unadjusted values not given		25(OH)D conc (nmol/l)	OR (95% CI)	No significant relationship seen between maternal 25(OH)D and risk of preterm birth using 3 different maternal 25(OH)D cut offs
												<37.5	0.97 (0.43, 2.21)
												<50	1.02 (0.48, 2.17)
												<75	0.79 (0.31, 2.06)
Hossain, 2011 120	4 (med)	Karachi, Pakistan Cohort=75 women Cases of preterm birth** = not given 26% of women covered their arms, hands and head; 76% also covered their face	Cross- sectional	None	At delivery	42.2 (19.5)+		32.9 (16.8)+		Not given		Not given		Maternal 25(OH)D tended to be higher in those who delivered preterm but did not achieve statistical significance (p=0.057)
Shibata, 2011 116	4 (med)	Toyoake, Japan Cohort size=93 women. Deliveries spread equally across seasons) Cases of threatened premature delivery △△=14	Cross- sectional	Maternal age, serum albumin, serum corrected calcium, serum bone specific ALP, serum Type 1 collagen N-terminal telopeptide, serum phosphate	At recruitment (>30 wks)	30.0 (8.0)		37.9 (12.7)		Not given		β=−0.019 (p=0.023)		Significantly lower maternal 25(OH)D in women with threatened premature delivery compared to normal deliveries. p for difference in means=0.002
Fernandez-Alonso, 2012 115	3 (med)	Almeria, Spain Cohort= 466 women Cases of preterm birth**= 33	Cohort	Nil	Between 11-14 weeks	25(OH)D conc (nmol/l)	n (%)	Not given		Not given		Not given		No significant relationship seen between maternal 25(OH)D and risk of preterm birth P=0.86
						<50	7 (21)
						50-74.9	15 (45)
						>75	11 (33)

^*No threshold for preterm birth given. Gestational age determined by the scoring system of Dubowitz (based on examination of the neonate and scored on neurological and physical examination features

^**Preterm birth defined as delivery at <37 weeks gestation

^***Severe preterm birth defined as delivery at <34 weeks gestation

^#Preterm birth defined as delivery at >23 weeks and <35 weeks gestation

⁺25(OH)D₃ measured

^△Defined as past obstetric history of early-onset or severe preeclampsia, unexplained elevated a-fetoprotein ≥ 2.5 multiples of the median (MoM), unexplained elevated human chorionic gonadatrophin, or low pregnancy-associated plasma protein A ≤ 0.6 MoM

^△△This study assessed risk of threatened premature delivery. Defined as progressive shortening of cervical length (<20 mm) as detected by transvaginal ultrasound before the 34^th week of gestation, and/or elevation of granulocyte elastase level in the cervical mucus before 32 weeks gestation; AND the number of uterine contractions equal to or more than twice per 30 minutes (before the 32^nd week of gestation)