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. 2016 Apr 15;74(6):387–410. doi: 10.1093/nutrit/nuv108

Table 4.

Studies included in the analysis that examined infectious disease

Reference Study location Study design, participants Exposure and summary statistics Main outcome measuresa
Belderbos et al. (2011)53 Utrecht, The Netherlands

  • Cohort study

  • 156 children

  • 68% white, 32% other

  • Mean cord 25(OH)D: 82 nmol/L (SE 3.5)

  • Cord blood 25(OH)D: RR (95%CI)

  • ≥75 vs <50 nmol/L

 RSV LRTI (reported + RSV swab) (0–1 y): 0.16 (0.04 to 0.63)
Camargo et al. (2011)32 Wellington and Christchurch, New Zealand

  • Cohort study

  • 922 children

  • 71% European, 14% Maori, 6% non-Maori Pacific Islander, 9% other

  • Median cord 25(OH)D: 44 nmol/L (IQR: 29–78)

  • Cord blood 25(OH)D: OR (95%CI)

  • ≥75 vs <25 nmol/L

  • Any respiratory infection (0–3 mo): 0.49 (0.27 to 0.89)

  • Any infection (0–3 mo): 0.42 (0.21 to 0.86)
Cetinkaya et al. (2015)59 Istanbul, Turkey

  • Case–control study

  • 50 cases of early-onset sepsis

  • 50 neonatal controls

  • Ethnicity not reported

  • Mean 25(OH)D not reported

  • Maternal 25(OH)D at ≤3 d postpartum: mean difference (SD)

  • Neonatal 25(OH)D at ≤3 d postpartum: mean difference (SD)

  • Clinical early-onset sepsis vs control (0–3 d)

  • Maternal: 55.4 (17.0) vs 90.4 (4.5) nmol/L, P < 0.001

  • Neonatal: 21.5 (7.7) vs 47.4 (12.0) nmol/L, P < 0.001

  • Culture-proven sepsis vs no culture (0–3 d)

  • Maternal: 67.6 (21.7) vs 54.2 (16.2) nmol/L, P = 0.09

  • Neonatal: 25.2 (4.5) vs 21.0 (8.0) nmol/L, P = 0.25
Chawes et al. (2014)30 Copenhagen, Denmark

  • Cohort study

  • 257 children

  • 98% white

  • Median cord 25(OH)D: 47.6 nmol/L (range, 10–145 nmol/L)

  • Cord blood 25(OH)D: HR (time to onset variable) and OR (95%CI)

  • >75 vs <50 nmol/L

  • LRTI (0–3 y)

  • Time to first LRTI: 0.93 y (0.54 to 1.61)

  • No. of LRTI: 1.06 (0.65 to 1.75)
Cizmeci et al. (2014)60 Istanbul, Turkey

  • Case–control study

  • 40 cases of early-onset sepsis

  • 43 neonatal controls

  • Ethnicity not reported

  • Mean 25(OH)D not reported

 Cord blood 25(OH)D: median difference Early-onset sepsis vs control (0–3 d): 31.5 vs 52.4 nmol/L, P = 0.038
Finkelstein et al. (2012)26 Dar es Salaam, Tanzania

  • Cohort study

  • 609 mother–child pairs

  • 100% African

  • All mothers HIV positive

  • Mean 25(OH)D not reported

  • Maternal 25(OH)D during 2nd trimester: RR (95%CI)

  • ≥80 vs <80 nmol/L

  • Cough (0–5 y)

  • Any: 0.90 (0.83 to 0.98)

  • With fever: 0.93 (0.79 to 1.08)

  • With rapid respiratory rate: 1.09 (0.74 to 1.61)

  • Plus other symptoms: 1.02 (0.81 to 1.30)

  • Diarrhea (0–5 y)

  • Any: 0.98 (0.83 to 1.15)

  • Acute: 1.00 (0.85 to 1.18)

  • Watery: 0.94 (0.75 to 1.19)

  • Dysenteric: 1.05 (0.83 to 1.32)
Finkelstein et al. (2010)27 Dar es Salaam, Tanzania

  • Cohort study

  • 884 mother–child pairs

  • 100% African

  • All mothers HIV positive

  • Mean 25(OH)D not reported

  • Maternal 25(OH)D during 2nd trimester: RR (95%CI)

  • ≥80 vs <80 nmol/L

  • Tuberculosis (0–2 y): 0.63 (0.99 to 0.41)

  • Cough (0–2 y): 0.83 (0.71 to 0.95)

  • Other respiratory symptoms (0–2 y): reported as NS

  • Diarrhea (0–2 y): reported as NS
Gad et al. (2015)61 Cairo, Egypt

  • Case–control study

  • 30 cases of congenital pneumonia

  • 30 neonatal controls

  • Ethnicity not reported

  • Mean 25(OH)D not reported

 Cord blood 25(OH)D: unpaired t test of mean difference (SD) Congenital pneumonia vs control (0–3 d): 86.94 (45.33) vs 232.63 (90.16) nmol/L, P = 0.0001
Gale et al. (2008)47 Southampton, United Kingdom

  • Cohort study

  • 596 mother–child pairs

  • 100% white

  • Median maternal 25(OH)D: 50 nmol/L (IQR: 30–75.3)

  • Maternal 25(OH)D during late pregnancy: OR (95%CI)

  • >75 vs <30 nmol/L

  • LRTI (0–9 mo): 4.80 (1.01 to 22.73)

  • Other respiratory illness: reported as NS

  • Any respiratory illness: reported as NS

  • Diarrhea (0–9 mo): 1.87 (1.01 to 3.46)
Goldring et al. (2013)35 London, United Kingdom

  • Randomized controlled trial (cord blood analysis done as cohort study)

  • 158 mother–child pairs

  • 23.7% white, 24.8% black, 25.6% Asian, 25.9% Middle Eastern

  • 50 in control group, 56 in daily-dose group (800 IU), 52 in bolus-dose group (200 000 IU, 1 time)

  • Median cord 25(OH)D: control group, 17 nmol/L (IQR: 14–22); daily-dose group, 26 nmol/L (IQR: 17–45); bolus-dose group, 25 nmol/L (IQR: 18–34)

  • Cord blood 25(OH)D: mean difference (95%CI) of the natural log of 25(OH)D between children with and children without outcome.

  • Combined 25(OH)D groups vs control: OR (95%CI)

  • Cord blood 25(OH)D:

  • LRTI (0–3 y): −0.10 ln(nmol/L) (−0.29 to 0.09)

  • >4 URTI per year (0–3 y): −0.11 ln(nmol/L) (−0.32 to 0.11)

  • Combined 25(OH)D groups vs control:

  • LRTI (0–3 y): 1.60 (0.67 to 3.85)

  • >4 URTI per year (0–3 y): 1.34 (0.49 to 3.68)
de Jongh et al. (2014)56 Southampton, United Kingdom

  • Cohort study

  • 2025 mother–child pairs

  • Ethnicity not reported

  • Median maternal 25(OH)D: 59.0 nmol/L (IQR: 40.6–84.3)

  • Maternal 25(OH)D at wk 34 of gestation: RR (95%CI)

  • <25 nmol/L

  • 25–49 nmol/L

  • 50–74 nmol/L

  • ≥75 nmol/L (reference)

  • LRTI (0–6 mo)

  • <25 nmol/L: 0.45 (0.24 to 0.84)

  • 25–49 nmol/L: 0.63 (0.49 to 0.81)

  • 50–74 nmol/L: 0.76 (0.58 to 0.99)

  • ≥75 nmol/L: 1.0 (reference)

  • LRTI (6–12 mo)

  • <25 nmol/L: 1.11 (0.72 to 1.71)

  • 25–49 nmol/L: 1.22 (0.97 to 1.54)

  • 50–74 nmol/L: 1.12 (0.87 to 1.42)

  • ≥75 nmol/L: 1.0 (reference)

  • LRTI (1–2 y)

  • <25 nmol/L: 0.69 (0.41 to 1.14)

  • 25–49 nmol/L: 0.98 (0.79 to 1.22)

  • 50–74 nmol/L: 0.92 (0.73 to 1.16)

  • ≥75 nmol/L: 1.0 (reference)

  • Otitis media (0–6 mo)

  • <25 nmol/L: 0.83 (0.41 to 1.69)

  • 25–49 nmol/L: 0.64 (0.40 to 1.01)

  • 50–74 nmol/L: 0.93 (0.61 to 1.93)

  • ≥75 nmol/L: 1.0 (reference)

  • Otitis media (6–12 mo)

  • <25 nmol/L: 1.29 (0.87 to 1.92)

  • 25–49 nmol/L: 1.13 (0.90 to 1.42)

  • 50–74 nmol/L: 1.18 (0.93 to 1.48)

  • ≥75 nmol/L: 1.0 (reference)

  • Otitis media (1–2 y)

  • <25 nmol/L: 1.07 (0.77 to 1.50)

  • 25–49 nmol/L: 0.95 (0.78 to 1.14)

  • 50–74 nmol/L: 1.04 (0.86 to 1.25)

  • ≥75 nmol/L: 1.0 (reference)

  • Diarrhea (0–6 mo)

  • <25 nmol/L: 0.99 (0.65 to 1.50)

  • 25–49 nmol/L: 0.93 (0.73 to 1.18)

  • 50–74 nmol/L: 1.05 (0.83 to 1.33)

  • ≥75 nmol/L: 1.0 (reference)

  • Diarrhea (6–12 mo)

  • <25 nmol/L: 0.91 (0.67 to 1.25)

  • 25–49 nmol/L: 0.96 (0.83 to 1.12)

  • 50–74 nmol/L: 1.0 (0.86 to 1.16)

  • ≥75 nmol/L: 1.0 (reference)

  • Diarrhea (1–2 y)

  • <25 nmol/L: 1.23 (0.95 to 1.57)

  • 25–49 nmol/L: 1.01 (0.87 to 1.18)

  • 50–74 nmol/L: 0.96 (0.82 to 1.13)

  • ≥75 nmol/L: 1.0 (reference)

  • Prolonged cough (0–6 mo)

  • <25 nmol/L: 0.33 (0.16 to 0.69)

  • 25–49 nmol/L: 0.68 (0.53 to 0.88)

  • 50–74 nmol/L: 0.80 (0.62 to 1.02)

  • ≥75 nmol/L: 1.0 (reference)

  • Prolonged cough (6–12 mo)

  • <25 nmol/L: 1.09 (0.73 to 1.62)

  • 25–49 nmol/L: 1.16 (0.95 to 1.42)

  • 50–74 nmol/L: 1.09 (0.89 to 1.35)

  • ≥75 nmol/L: 1.0 (reference)

  • Prolonged cough (1–2 y)

  • <25 nmol/L: 0.82 (0.52 to 1.29)

  • 25–49 nmol/L: 1.19 (0.97 to 1.45)

  • 50–74 nmol/L: 1.07 (0.86 to 1.33)

  • ≥75 nmol/L: 1.0 (reference)
Luczynska et al. (2014)55 Ulm, Germany

  • Cohort study

  • 777 children

  • Ethnicity not reported

  • Mean 25(OH)D not reported

  • Cord blood 25(OH)D: RR (95%CI)

  • <25 nmol/L

  • 25–50 nmol/L

  • >50 nmol/L (reference)

  • Q1: 16.9 nmol/L

  • Q2: 16.9–26.5 nmol/L

  • Q3: 26.5–43.3 nmol/L

  • Q4: >43.3 nmol/L (reference)

  • LRTI (0–1 y)

  • <25 nmol/L: 1.32 (1.00 to 1.73)

  • 25–50 nmol/L: 1.11 (0.83 to 1.48)

  • >50 nmol/L: 1.0 (reference)

  • Q1: 1.23 (0.95 to 1.59)

  • Q2: 1.28 (0.99 to 1.66)

  • Q3: 1.11 (0.84 to 1.46)

  • Q4: 1.0 (reference)
Magnus et al. (2013)33 Norway

  • Cohort study (with additional targeted recruitment of asthma cases)

  • 1248 mother–child pairs

  • Ethnicity not reported

  • Mean maternal 25(OH)D: 73.7 nmol/L (SD 23.7)

  • Maternal mid-pregnancy 25(OH)D: OR (95%CI)

  • 20 nmol/L increments

  • LRTI frequency (0–3 y)

  • 1–2 episodes: 0.98 (0.87 to 1.12)

  • ≥3 episodes: 0.74 (0.58 to 0.93)
Mohamed et al. (2013)54 Abha, Saudi Arabia

  • Cohort study

  • 206 children

  • Ethnicity not reported

  • 14.1% dark maternal skin

  • Mean cord 25(OH)D: 60.1 nmol/L (SD 4.8)

  • Cord blood 25(OH)D: mean difference (with and without LRTI), OR (95%CI)

  • >75 vs <75 nmol/L

  • LRTI (0–2 y)

  • Mean difference: 33.9 vs 71.4 nmol/L, P < 0.001

  • OR: 0.93 (0.91 to 0.95)
Morales et al. (2012)40 Menorca Island, Valencia, Sabadell, and Gipuzkoa, Spain

  • Cohort study

  • 1693 mother–child pairs

  • 97% white, 3% other

  • Median maternal 25(OH)D: 73.6 nmol/L (IQR: 56.2–92.6)

  • Maternal 25(OH)D at about week 13 of gestation: OR nmol/L (95%CI)

  • Q1: <54.6 nmol/L (reference)

  • Q2: 54.6–72.6 nmol/L

  • Q3: 72.7–92.4 nmol/L

  • Q4: >92.4 nmol/L

  • LRTI (0–1 y)

  • Q1: 1.0 (reference)

  • Q2: 0.89 (0.67 to 1.19)

  • Q3: 0.92 (0.70 to 1.23)

  • Q4: 0.67 (0.50 to 0.90)
Shin et al. (2013)57 South Korea

  • Cohort study

  • 525 children

  • Ethnicity not reported

  • Mean cord 25(OH)D: 32.0 nmol/L (IQR: 21.4–53.2)

  • Cord blood 25(OH)D: OR (95%CI)

  • ≥75 nmol/L (reference)

  • 25–74.9 nmol/L

  • <25 nmol/L

  • Any respiratory tract infection (6 mo)

  • ≥75 nmol/L: 1.0 (reference)

  • 25–74.9 nmol/L: 2.06 (0.91 to 4.64)

  • <25 nmol/L: 3.56 (1.52 to 8.34)

  • Acute nasopharyngitis (6 mo)

  • ≥75 nmol/L: 1.0 (reference)

  • 25–74.9 nmol/L: 2.99 (1.13 to 7.93)

  • <25 nmol/L: 5.21 (1.91 to 14.27)

  • Otitis media (6 mo)

  • ≥75 nmol/L: 1.0 (reference)

  • 25–74.9 nmol/L: 2.79 (0.35 to 22.05)

  • <25 nmol/L: 2.83 (0.33 to 23.91)

  • Bronchiolitis (6 mo)

  • ≥75 nmol/L: 1.0 (reference)

  • 25–74.9 nmol/L: 2.98 (0.38 to 23.16)

  • <25 nmol/L: 2.65 (0.32 to 22.20)
Skowronsk a-Jozwiak et al. (2014)58 Lodz, Poland

  • Cohort study

  • 69 mother–child pairs

  • Ethnicity not reported

  • Mean 25(OH)D not reported

  • Maternal 25(OH)D during 3rd trimester: chi-square test

  • >74.9 nmol/L

  • 49.9–74.9 nmol/L

  • <49.9 nmol/L

  • Recurrent respiratory tract infections (1 y)

  • >74.9 nmol/L vs <49.9 nmol/L: P = 0.003

  • >74.9 nmol/L vs 49.9–74.9 nmol/L: P = 0.040

  • 49.9–74.9 nmol/L vs <49.9 nmol/L: P = 0.200
Stelmach et al. (2015)45 Poland

  • Cohort study

  • 190 children

  • Ethnicity not reported

  • Median cord 25(OH)D: 15.8 nmol/L (IQR: 10.4–21.3)

  • Cord blood 25(OH)D: OR (95%CI)

  • Continuous variable > vs < median > vs < lower quartile

  • More than 1 respiratory tract infection (2 y)

  • Continuous 25(OH)D: 1.52 (0.33 to 6.94) > vs < median 25(OH)D: 0.89 (0.47 to 1.67) > vs < lower quartile 25(OH)D: 1.05 (0.51 to 2.17)

Abbreviations: CI, confidence interval; IQR, interquartile range; LRTI, lower respiratory tract infection; NS, not significant; OR, odds ratio; RR, relative risk; RSV, respiratory syncytial virus; SD, standard deviation; SE, standard error; URTI, upper respiratory tract infection.

aAll statistics are after maximal adjustment. Values significant at the P = 0.05 level are shown in bold type.