Table 19. The effect of maternal vitamin D status in gestation on risk of offspring being born small for gestational age – 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 SGA infants | Maternal mean (SD) 25(OH)D concentration (nmol/l) in infants appropriate for GA (AGA) | Odds ratio (95% CI) of offspring being SGA from univariate analysis | Odds ratio (95% CI) of offspring being SGA from multivariate analysis | Conclusion | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Akcakus, 2006 100 | 4 (med) | Turkey Cohort=100 women Cases of SGA*=30 Most women veiled |
Cross- sectional |
NIl | Delivery | 21.75 (7.5) | 21.5 (7.5) | Not given | Not given | No difference in maternal 25(OH)D at delivery in SGA infants compared to AGA infants | |||
| Mehta, 2009 118 | 3 (med) | Tanzania Overall Cohort=1078. Women all HIV infected taking part in a clinical trial of vitamin use Cases of SGA*=74 Cohort for analysis= 675 |
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 44.6% had 25(OH)D <80 nmol/l 55.4% had 25(OH) D >80 nmol/l |
Mean not given | 1.25 (0.81, 1.91) p=0.31 |
1.25 (0.82, 1.90) p=0.31 |
No relationship between SGA risk and maternal 25(OH)D amongst women with HIV | |||
| Leffelaar, 2010 82 | 5 (low) | Amsterdam Born Children and their development (ABCD) study, Netherlands Cohort=3730 women Cases of SGA*=9.2% (approx. 343) |
Prospective cohort |
2 models OR1 adjusted for gestational age, season of collection, sex, maternal parity, maternal age, smoking, pre-pregnancy BMI, educational level OR2 additional adjustment for ethnic group and vitamin D status |
Early pregnancy (mean 13 weeks) | Not given | Not given | Crude OR adjusted for season of blood sample and gestational age | After adjusting for confounders, women with 25(OH)D <30 have a significantly increased risk of SGA infant | ||||
| 25(OH)D nmol/l | Crude OR (95% CI) | OR1 (95% CI) | OR2 (95% CI) | ||||||||||
| <30 | 2.4 (1.0-3.2) | 1.8 1.3-2.5 | 1.9 (14-2.7) | ||||||||||
| 30-49.9 | 1.5 (1.1-2.0) | 1.2 0.9-1.7 | 1.2 (0.9-1.3) | ||||||||||
| 50+ | 1.0 (Ref) | 1.0 (Ref) | 1.0 (Ref) | ||||||||||
| Bodnar, 2010 112 | 7 (low) | Pittsburg, USA Overall cohort size=1198 women Cases of SGA*=111 Controls=301 |
Nested case-control |
Pre-pregnancy BMI, smoking during pregnancy, socioeconomic score. Additional adjustments for season, maternal age, gestational age at blood sampling, marital status, insurance status, smoking pre=pregnancy, pre conceptual multivitamin use, preconception physical activity had no meaningful impact on results |
<22 weeks | Geometric mean (95% CI) according to race White= 73.2 (69.7, 76.8) Black=39.8 (36.7, 43.2) |
Geometric mean (95% CI) according to race White= 71.5 (64.0, 79.9) Black= 39.8 (33.6, 47.0) |
OR broken down according to race | Adjusted OR broken down according to race | No relationship between SGA risk and maternal 25(OH)D amongst black mothers No sig. difference in the geometric means of 25(OH)D in white women with and without SGA infants. A u-shaped relation was seen between SGA risk and maternal 25(OH)D amongst white mothers with the lowest risk between 6080 nmol/l |
|||
| 25(OH)D Nmol/l | White | Black | White | Black | |||||||||
| <37.5 | 10.6 (2.6, 42.5) | 1.4 (0.5, 3.1) | 7.5 (1.8, 31.9) | 1.5 (0.6, 3.5) | |||||||||
| 37.5-75 | 1.0 (ref) | 1.0 (Ref) | 1.0 (ref) | 1.0 (ref) | |||||||||
| >75 | 1.9 (1.1, 3.4) | 1.9 (1.1, 3.4) | 2.1 (1.2, 6.8) | 2.2 (0.5, 5.5 | |||||||||
| Shand, 2010 114 | 6 (low) | Vancouver, Canada All women had either clinical or biochemical risk factors for preeclampsia△ Cohort=221 women Cases of SGA**=13 |
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 | OR (95% CI) | No significant relationship seen between maternal 25(OH)D and risk of infant being SGA | ||
| <37.5 | 1.78 (0.52, 6.03) | ||||||||||||
| <50 | 2.34 (0.65, 8.49) | ||||||||||||
| <75 | 2.16 (0.26, 18.2) | ||||||||||||
| Robinson 2011 113 | 1 (med) | South Carolina, USA All women has early onset preeclampsia (EOSPE)△△ Cases=33 Controls=23 |
Case-control | No significant differences between cases and controls in terms of maternal age, nulliparity, African-American race, mean arterial blood pressure, BMI. Cases had significantly higher age at gestation, therefore all birth weights converted to percentile growth for gestational age |
Not given | 41.9 (22.2-57.4) | 63.1 (39.9-82.4) | Not given | Not given | Serum 25(OH)D significantly lower in women with EOSPE and SGA offspring compared to EOSPE controls with normal sized offspring p=0.02 | |||
|
Fernandez-Alonso, 2012 115 |
3 (med) | Almeria, Spain Cohort=466 women Cases of SGA* =46 |
Cohort | Nil | Between 11-14 weeks | Overall mean not given | Not given | Not given | Not given | No significant relationship seen between maternal 25(OH)D and risk of infant being SGA p=0.78 | |||
*
SGA defined as infants born <10th percentile of birth weight according to nomograms based on gender and gestational age
**
SGA defined as infants born <3rd percentile of birth weight according to nomograms based on gender and gestational age
△
Defined as past obstetric history of early-onset or severe preeclampsia, unexplained elevated α-fetoprotein ≥ 2.5 multiples of the median (MoM), unexplained elevated human chorionic gonadatrophin, or low pregnancy-associated plasma protein A ≤ 0.6 MoM
△△
Defined as meeting the American College of Obstetrics and Gynecology criteria for severe preeclampsia and having this diagnosis at <34 weeks gestation