What do systematic reviews say?

Higher mean patient age (per 1 year) vs Lower mean patient age (per 1-year decrement)

In the mandible, mean patient age was not significantly associated with space closure odds (OR 0.59 per year; not GRADE-rated).

• Spontaneous space closure after extraction of permanent first molars in children and adolescents: a systematic review… 2024 All outcomes

  Until eruption of the permanent second molar (median follow-up 4.0 years) · University clinics and hospitals in 8 countries (children/adolescents <18 years) · Mandible
  OR 0.59 [0.20, >100.00]
  3 studies
  GRADE not reported

Higher parental / maternal education vs Lower parental education (reference)

Higher parental education is associated with better OHRQoL in adolescents (narrative synthesis; no pooled estimate or GRADE rating).

• Oral-health-related quality of life in adolescents: umbrella review. 2023 All outcomes

  Community/school/clinic settings; adolescents 10-19 years; included reviews conducted in multiple countries
  Adolescents from families with higher incomes and higher levels of maternal education have better OHRQoL scores [34]. Children from families with high income, parental education and family economy had better OHRQoL [42].
  Studies not reported
  GRADE not reported

A dose of vitamin D 601 IU or higher vs 600 IU or lower alone or with other nutrients

A dose of vitamin D 601 IU or higher showed no clear difference in pre‐eclampsia compared with 600 IU or lower alone or with other nutrients (low certainty).

• Regimens of vitamin D supplementation for women during pregnancy 2019 · Cochrane Headline outcomes only
  RR 0.96 [0.65, 1.42]
  5 studies · 1553 participants
  Low

A dose of vitamin D 601 IU or higher vs 600 IU or lower alone or with other nutrients

A dose of vitamin D 601 IU or higher probably leads to lower gestational diabetes compared with 600 IU or lower alone or with other nutrients (moderate certainty).

• Regimens of vitamin D supplementation for women during pregnancy 2019 · Cochrane Headline outcomes only
  RR 0.54 [0.34, 0.86]
  5 studies · 1846 participants
  Moderate

A dose of vitamin D 601 IU or higher vs 600 IU or lower alone or with other nutrients

A dose of vitamin D 601 IU or higher showed no clear difference in preterm birth compared with 600 IU or lower alone or with other nutrients (low certainty).

• Regimens of vitamin D supplementation for women during pregnancy 2019 · Cochrane Headline outcomes only
  RR 1.25 [0.92, 1.69]
  4 studies · 2294 participants
  Low

A dose of vitamin D 601 IU or higher vs 600 IU or lower alone or with other nutrients

It is very uncertain whether A dose of vitamin D 601 IU or higher changes low birthweight compared with 600 IU or lower alone or with other nutrients (very low certainty).

• Regimens of vitamin D supplementation for women during pregnancy 2019 · Cochrane Headline outcomes only
  RR 0.9 [0.66, 1.24]
  4 studies · 1550 participants
  Very low

Anticipated normal responders: higher vs lower dose of FSH

• Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro… 2024 · Cochrane Headline outcomes only
  no estimate extracted
  1 study · 37 participants
  GRADE not reported

Anticipated normal responders: higher vs lower dose of FSH

Anticipated normal responders: higher showed no clear difference in IU vs 100 IU compared with lower dose of FSH (low certainty).

• Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro… 2024 · Cochrane Headline outcomes only
  OR 0.88 [0.57, 1.36]
  2 studies · 522 participants
  Low

Anticipated normal responders: higher vs lower dose of FSH

Anticipated normal responders: higher showed no clear difference in 225/200 IU vs 150 IU compared with lower dose of FSH (low certainty).

• Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro… 2024 · Cochrane Headline outcomes only
  OR 0.98 [0.7, 1.36]
  2 studies · 686 participants
  Low

Anticipated normal responders: higher vs lower dose of FSH

Anticipated normal responders: higher showed no clear difference in IU vs 225 IU compared with lower dose of FSH (low certainty).

• Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro… 2024 · Cochrane Headline outcomes only
  OR 0.65 [0.32, 1.32]
  1 study · 135 participants
  Low

Rabeprazole at higher doses (1 mg/kg) vs rabeprazole at lower doses (0.5 mg/kg)

• Pharmacological treatment of gastro‐oesophageal reflux in children 2023 · Cochrane Headline outcomes only
  no estimate extracted
  1 study · 127 participants
  Very low

Rabeprazole at higher doses (1 mg/kg) vs rabeprazole at lower doses (0.5 mg/kg)

• Pharmacological treatment of gastro‐oesophageal reflux in children 2023 · Cochrane Headline outcomes only
  no estimate extracted
  1 study · 127 participants
  Very low

Rabeprazole at higher doses (1 mg/kg) vs rabeprazole at lower doses (0.5 mg/kg)

• Pharmacological treatment of gastro‐oesophageal reflux in children 2023 · Cochrane Headline outcomes only
  no estimate extracted
  1 study · 127 participants
  Very low

Rabeprazole at higher doses (1 mg/kg) vs rabeprazole at lower doses (0.5 mg/kg)

The review found no eligible studies for this question.

• Pharmacological treatment of gastro‐oesophageal reflux in children 2023 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

The meta-analysis of observational studies reported a SMD (to OR) of 0.08 (95% CI 0.01 to 0.63) for higher versus lower circulating vitamin D concentration.

• Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational… 2014 All outcomes
  SMD (to OR) 0.08 [0.01, 0.63]
  7 studies · 1005 participants
  GRADE not reported

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

The meta-analysis of observational studies reported a OR of 0.88 (95% CI 0.68 to 1.15) for higher versus lower circulating vitamin D concentration.

• Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational… 2014 All outcomes
  OR 0.98 [0.84, 1.15]
  6 studies · 4524 participants
  GRADE not reported

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

The meta-analysis of observational studies reported a SMD (to OR) of 0.29 (95% CI 0.19 to 0.46) for higher versus lower circulating vitamin D concentration.

• Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational… 2014 All outcomes
  SMD (to OR) 0.29 [0.19, 0.46]
  7 studies · 534 participants
  GRADE not reported

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

The meta-analysis of observational studies reported a SMD (to OR) of 0.31 (95% CI 0.23 to 0.42) for higher versus lower circulating vitamin D concentration.

• Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational… 2014 All outcomes
  SMD (to OR) 0.31 [0.23, 0.42]
  28 studies · 2956 participants
  GRADE not reported

Higher circulating 25-hydroxyvitamin D (25(OH)D) concentration vs Lower circulating 25-hydroxyvitamin D (25(OH)D) concentration

The meta-analysis of observational studies reported a RR of 0.88 (95% CI 0.81 to 0.93) for higher versus lower circulating vitamin D concentration.

• Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational… 2014 All outcomes
  RR 0.86 [0.81, 0.92]
  10 studies · 6853 participants
  GRADE not reported

Higher drinking-water fluoride exposure vs Null / lowest drinking-water fluoride exposure (reference)

Non-linear positive dose-response: little change in overall fracture risk below ~1.5 mg/L drinking-water fluoride, with risk increasing above that threshold (RR 1.06, 1.19, 1.35 at 2.0, 3.0, 4.0 mg/L vs null); ungraded (4 studies).

• The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes

  Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Drinking-water fluoride 1.2 mg/L vs null
  RR 1.00 [0.80, 1.24]
  4 studies
  GRADE not reported
• The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes

  Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Drinking-water fluoride 4.0 mg/L vs null
  RR 1.35 [0.94, 1.95]
  4 studies
  GRADE not reported
• The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis. 2025 All outcomes

  Long-term / lifetime fluoride exposure · General population; 37 observational studies (1944-2024), predominantly North America (USA, Canada) and Northern Europe (Finland, Sweden), plus UK, Poland, Italy, Germany, China, Taiwan, South Korea, Ethiopia; exposure mainly community drinking-water fluoride · Drinking-water fluoride 3.0 mg/L vs null
  RR 1.19 [0.87, 1.64]
  4 studies
  GRADE not reported