Nutritional advice

Objectives:
The efficacy of myo-inositol supplementation to prevent gestational diabetes onset remains controversial. Therefore, this meta-analysis (systematic review) has been conducted.

Does myo-inositol supplementation reduce risk of gestational diabetes in pregnant women?

Study design:
This review article included 5 RCTs.

Results and conclusions:
The investigators found compared with control group in pregnant women, myo-inositol supplementation significantly reduced risk of gestational diabetes with 57% [risk ratio = 0.43, 95% CI = 0.21-0.89, p = 0.02].

The investigators found compared with control group in pregnant women, myo-inositol supplementation significantly reduced risk of preterm delivery with 64% [risk ratio = 0.36, 95% CI = 0.17-0.73, p = 0.005].

The investigators found compared with control group in pregnant women, no association between myo-inositol supplementation and 2-h glucose oral glucose tolerance test (OGTT) [mean difference = -6.90, 95% CI = -15.07 to 1.27, p = 0.10].

The investigators found compared with control group in pregnant women, no association between myo-inositol supplementation and gestational age at birth [MD = 0.74, 95% CI = -1.06 to 2.54, p = 0.42].

The investigators found compared with control group in pregnant women, no association between myo-inositol supplementation and birth weight [MD = -5.50, 95% CI = -116.99 to 105.99, p = 0.92].

The investigators found compared with control group in pregnant women, no association between myo-inositol supplementation and macrosomia (a newborn with an excessive birth weight (≥4 kg)) [RR = 0.65, 95% CI = 0.20-2.11, p = 0.47].

The investigators concluded that myo-inositol supplementation reduces the incidence of gestational diabetes and preterm delivery in pregnant women.

Original title:
The efficacy of myo-inositol supplementation to prevent gestational diabetes onset: a meta-analysis of randomized controlled trials by Zhang H, Lv Y, […], Guo W.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29343138

Additional information of El Mondo:
Find more information/studies on inositol and pregnancy right here.

A review article (a collection of scientific studies on a specific topic) of randomized, placebo-controlled double blind clinical trials (RCTs) will answer the following question:
"Do taking dietary supplements make sense?" Yes for a positive conclusion and no for a negative conclusion.

Objectives:
Anemia is a major public health and nutritional problem in the world. Studies have reported the relationship between anemia during pregnancy and small for gestational age (SGA). Therefore, this meta-analysis (systematic review) has been conducted.

Does maternal anemia during pregnancy increase risk of SGA?

Study design:
This review article included 10 studies with a total of 620,080 pregnant women.

Results and conclusions:
The investigators found the overall relationship between maternal anemia during pregnancy and SGA was not significant [RR = 1.11, 95% CI = 0.99-1.24, p = 0.074].
Not significant means that there is no association with a 95% confidence.

The investigators found, however, a significantly increased risk of 11% [RR = 1.11, 95% CI = 1.00-1.22, p = 0.044] of SGA for materal anemia during first trimester. But this relationship was not significant in the second trimester [RR = 1.11, 95% CI = 0.85-1.18, p = 0.91].

The investigators concluded maternal anemia in the first trimester of pregnancy increases risk of small for gestational age (SGA).

Original title:
Maternal anemia during pregnancy and small for gestational age: a systematic review and meta-analysis by Badfar G, Shohani M, […], Azami M.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29183181

Additional information of El Mondo:
Find more information/studies on anemia and pregnancy right here.
 

Objectives:
Observationally, homocysteine is associated with higher risk of diabetes. Folate, which reduces homocysteine, is promising for the prevention and treatment of diabetes. Previous meta-analysis (review) of 3 trials suggested folate might lower hemoglobin A1c (HbA1c). Therefore, this review article (meta-analysis) has been conducted.

Have folic acid supplementation positive effects on insulin resistance and glycemic control, like HbA1c level and fasting glucose level?

Study design:
This review article included 18 RCTs with in total of 21,081 people with/without diabetes.

Results and conclusions:
The investigators found that folic acid (folate) supplementation significantly reduced fasting glucose level with 0.15 mmol/L [95% CI = -0.29 to -0.01]. Significant means that there is an association with a 95% confidence.

The investigators found that folic acid (folate) supplementation significantly reduced homeostatic model assessment-insulin resistance (HOMA-IR) with 0.83 [95% CI = -1.31 to -0.34].

The investigators found that folic acid (folate) supplementation significantly reduced fasting insulin level with 1.94 μIU/mL [95% CI = -3.28 to -0.61].

The investigators found that folic acid (folate) supplementation had no clear effect on diabetes or HbA1c level.

The investigators concluded that folic acid (folate) supplementation reduces both fasting glucose level, fasting insulin level and homeostatic model assessment-insulin resistance (HOMA-IR) but it has no effect on diabetes or HbA1c level.

Original title:
The effects of folate supplementation on glucose metabolism and risk of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials by Zhao JV, Schooling CM and Zhao JX.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29501221

Additional information of El Mondo:
Find more information/studies on diabetes and folic acid right here.

Patients with diabetes often have both an increased fasting glucose level, HOMA-IR value and fasting insulin level.

Objectives:
The increasing prevalence of diabetes in the United Kingdom and worldwide calls for new approaches to its management and diets with low glycaemic index have been proposed as a useful means for managing glucose response. However, there are conflicting reports and differences in the results of studies in terms of their effectiveness. Furthermore, the impact of low-glycaemic index diets (low GI-diets) and their long-term use in patients with type 2 diabetes remains unclear. Therefore, this review article (meta-analysis) has been conducted.

Do patients with type 2 diabetes mellitus benefit from low-GI diets?

Study design:
This review article included 6 RCTs.

Results and conclusions:
The investigators found in 2 RCTs that low-glycaemic index (low-GI) diet resulted in a significant improvement in glycated haemoglobin (HbA1c) [0.05]:
low-GI diet Δ = -0.5% [95% CI = -0.61% to -0.39%] vs. high-cereal fibre diet Δ = -0.18% [95% CI = -0.29% to -0.07%] and;
low-GI legume diet Δ = -0.5% [95% = -0.6% to -0.4%] vs. high-wheat fibre diet Δ = -0.3% [95% Cl = -0.4 to -0.2%].

The investigators found in 4 RCTs significant improvements in fasting blood glucose in low-GI diets compared to higher-GI diets or control:
low-GI diet = [150.8 ± 8.7] vs. higher-GI diet = [157.8 ± 10.4 mg/dL, mean ± SD, p = 0.43];
low-GI diet = [127.7] vs. high-cereal fibre diet = [136.8 mg/dL, p = 0.02];
low-GI diet = [6.5 (5.6-8.4)] vs. standard diabetic diet = [6.7 (6.1-7.5 mmol/L), median and interquartile range p > 0.05] and;
low-GI diet = [7.3 ± 0.3] vs. conventional carbohydrate exchange diet = [7.7 ± 0.4 mmol/L, mean ± SEM (Standard Error of Mean), p 0.05].

The investigators concluded that the low-GI diet is more effective in controlling glycated haemoglobin (HbA1c) and fasting blood glucose compared with a higher-GI diet or control in patients with type 2 diabetes. It will useful to evaluate the long-term effectiveness of low-glycaemic index diet in patients with type 2 diabetes.

Original title:
The Effect of Dietary Glycaemic Index on Glycaemia in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials by Ojo O, Ojo OO, [...], Wang XH.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872791/

Additional information of El Mondo:
Find more information/studies on diabetes and GI-diets right here.

A low-GI diet is a diet with a lot of products/meals with a low GI.
Products/meals with a low GI are products/meals with a GI-number of 55 or less.
In daily life, products/meals with a low GI contain at least 1.5 grams fiber per 100 kcal. These products and meals contain at least 1.5 grams fiber per 100 kcal.
 

Objectives:
Type 2 diabetes mellitus (T2DM) is one of the most important public health issues. Vitamin K supplementation might have favorable effect on risk factors of T2DM. Therefore, this review article (meta-analysis) has been conducted.

Have vitamin K supplementation favorable effects on risk factors of type 2 diabetes mellitus?

Study design:
This review article included 5 RCTs with in total of 533 participants.

There was no evidence of publication bias.

Results and conclusions:
The investigators found overall, meta-analysis did not show any beneficial effect of vitamin K supplementation on both:
-fasting blood sugar levels [-0.91 mg/dL, 95% CI = -2.57 to 0.76, p = 0.28];
-fasting insulin levels [-0.35 μIU/mL, 95% CI = -1.70 to 1.00, p = 0.61];
-HOMA-IR [-0.06, 95% CI = -0.32 to -0.19, p = 0.63] and
-2-h oral glucose tolerance test [-4.00 mg/dL, 95% CI = -20.00 to 11.99, p = 0.62].

The investigators found sensitivity analysis showed that overall estimates were not affected by elimination of any study.

The investigators concluded that vitamin K supplementation has no significant effect on glycemic control in healthy subjects. However, further studies should be performed on diabetic and pre-diabetic patients to determine the effect of vitamin K supplementation on impaired glycemic control.

Original title:
Effect of Vitamin K Supplementation on Glycemic Control: A Systematic Review and Meta-Analysis of Clinical Trials by Shahdadian F, Mohammadi H and Rouhani M.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29523009

Additional information of El Mondo:
Find more information/studies on diabetes and vitamin K right here.
 

Objectives:
The actual effects of L-carnitine administration on leptin serum level is inconsistent. Therefore, this review article (meta-analysis) has been conducted.

Does L-carnitine supplementation reduce leptin serum level?

Study design:
This review article included 7 RCTs with 325 cases (group with L-carnitine administration) and 330 controls (group without L-carnitine administration).

Subgroup analysis to find the sources of heterogeneity showed that L-carnitine dosage [ 2 g: I2 = 00.0%, p = 0.408] and study population [diabetes: I2 = 46.7%, p = 0.153 and non-diabetes: I2 = 15.1%, p = 0.317] were the potential sources of heterogeneity.

Results and conclusions:
The investigators found that L-carnitine supplementation had no significant effect on serum leptin concentrations [WMD = -0.565 ng/mL, 95% CI = -2.417 to 1.287, p = 0.550, I2 = 84.3%, p  0.0001].

The investigators found in subgroup analysis that  ≥ 2 mg L-carnitine supplementation significantly reduced serum leptin concentrations [WMD = -2.742 ng/mL, 95% CI = -3.039 to -2.444, p  0.001].

The investigators found in subgroup analysis that L-carnitine supplementation significantly reduced serum leptin concentrations in diabetic patients [WMD = -2.946 ng/mL, 95% CI = -3.254 to -2.638, p  0.001].

The investigators found in subgroup analysis that L-carnitine supplementation during 12 weeks significantly reduced serum leptin concentrations [WMD = -2.772 ng/mL, 95% CI = -3.073 to -2.471, p  0.001].

The investigators concluded that at least 3 mg L-carnitine per day in the course of 12 weeks reduce serum leptin concentrations, especially in diabetic patients.

Original title:
The effect of L-carnitine supplementation on serum leptin concentrations: a systematic review and meta-analysis of randomized controlled trials by Nazary-Vannani A, Ghaedi E, […], Varkaneh HK.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29453657

Additional information of El Mondo:
Find more information/studies on diabetes and L-carnitine and diabetes right here.

L-carnitine is a non-essential amino acid, which is also found in foods.

Objectives:
Fish oil supplementation has been shown to be associated with a lower risk of metabolic syndrome and benefit a wide range of chronic diseases, such as cardiovascular disease, type 2 diabetes and several types of cancers. However, the evidence of fish oil supplementation on glucose metabolism and insulin sensitivity is still controversial. Therefore, this review article (meta-analysis) has been conducted.

Does fish oil supplementation improve insulin sensitivity in humans?

Study design:
This review article included a total of 17 RCTs with 672 participants. One of the 17 studies was crossover design and others were parallel design.
The doses of active ingredients of fish oil (n-3 fatty acids) ranged from 1 g/d to 4 g/d. Duration of the interventions was ranged from 4 weeks to 24 weeks.
There was no suggestion of small study effect based on visual inspection of the funnel plot. Results of the Egger’s (p = 0.78) and Begg’s (p = 0.43) tests showed that there was no potential publication bias.

Results and conclusions:
The investigators found pooled analysis showed that fish oil supplementation had no effects on insulin sensitivity overall [SMD = 0.17, 95% CI = -0.15 to 0.48, p = 0.292, I2 = 58.1%, p = 0.001].

The investigators found subgroup analysis showed that fish oil supplementation significantly improved insulin sensitivity among people who were experiencing at least one symptom of metabolic disorders [SMD = 0.53, 95% CI = 0.17 to 0.88, p 0.001].

The investigators found subgroup analysis showed a positive effect of fish oil on insulin sensitivity among the short-term intervention group (12 weeks) rather than the long-term intervention group [SMD = 0.31, 95% CI = 0.01-0.61, p = 0.04].

The investigators found subgroup analysis showed that fish oil had no effects on insulin sensitivity among the healthy people or people with T2DM.

The investigators found there were no significant differences between subgroups of methods of insulin sensitivity and doses of omega-3 polyunsaturated fatty acids (n-3 PUFA) of fish oil supplementation.

The investigators found in sensitivity analysis that summary results did not differ significantly when omitting studies one at a time.

The investigators concluded that fish oil supplementation during 12 weeks improves insulin sensitivity among people who were experiencing at least one symptom of metabolic disorders.

Original title:
Fish oil supplementation and insulin sensitivity: a systematic review and meta-analysis by Gao H, Geng T, [...], Zhao Q.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496233/

Additional information of El Mondo:
Find more information/studies on fish oil supplements and diabetes right here.

 

Objectives:
Does breastfeeding reduce risk of endometrial cancer?

Study design:
This review article included individual-level data from 3 cohort and 14 case-control studies, with a total of  8,981 women with endometrial cancer and 17,241 women in a control group.

Results and conclusions:
The investigators found ever breastfeeding was associated with an 11% reduction in risk of endometrial cancer [pooled OR = 0.89, 95% CI = 0.81-0.98].
The association with ever breastfeeding was not explained by greater parity and did not vary notably by body mass index or histologic subtype (grouped as endometrioid and mucinous compared with serous and clear cell).

The investigators found longer average duration of breastfeeding per child was associated with lower risk of endometrial cancer, although there appeared to be some leveling of this effect beyond 6-9 months.

The investigators concluded that reducing endometrial cancer risk can be added to the list of maternal benefits associated with breastfeeding. Ongoing promotion, support and facilitation of this safe and beneficial behavior might therefore contribute to the prevention of this increasingly common cancer.

Original title:
Breastfeeding and Endometrial Cancer Risk: An Analysis From the Epidemiology of Endometrial Cancer Consortium by Jordan SJ, Na R, […], Webb PM.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28486362

Additional information of El Mondo:
Find more information/studies on cancer and pregnancy right here.
 

Objectives:
The potential glucose-lowering effects of pomegranate have been reported in animal and observational studies, but intervention studies in humans have generated mixed results. Therefore, this review article (meta-analysis) has been conducted.

What are the effects of pomegranate supplementation on measures of glucose control, insulin levels and insulin sensitivity in humans?

Study design:
This review article included 16 RCTs with 538 subjects. 14 trials adopted parallel study designs and the 2 remaining trials used crossover designs.
The total number of subjects included in each study ranged from 14 to 74 subjects.
The mean age of participants in each trial ranged from 30 to 70 years, with differing age ranges in most studies.
11 studies used pomegranate juice as a supplement (the dosage ranged from 120 to 500 ml/day).
2 studies used pomegranate seed oil as treatments (the dosage ranged from 400 to 2000 mg/day).
3 studies utilized pomegranate extract as the intervention (the dosage ranged from 710 to 1420 mg/day).  
The duration of the pomegranate intervention varied from 1 to 12 weeks (median: 5.5 weeks).

Overall, significant heterogeneity was detected for FBI and HOMA-IR, but subgroup analysis could not identify factors significantly influencing these parameters.
No significant publication bias was found.

Results and conclusions:
The investigators found that pomegranate did not significantly affect the measures of:
-FBG (fasting blood glucose) [WMD = -0.6 mg/dL, 95% CI = -2.79 to 1.58, p = 0.59, I2 = 0%];
-FBI (fasting blood insulin) [WMD = 0.29 μIU/mL, 95% CI = -1.16 to 1.75, p = 0.70, I2 = 60.4%];
-HOMA-IR (homeostatic model assessment of insulin resistance) [WMD = -0.04, 95% CI = -0.53 to 0.46, p = 0.88, I2 = 59.8%] or;
-HbA1c (glycated haemoglobin) [WMD = -0.11%, 95% CI = -0.39 to 0.18, p = 0.46, I2 = 0%].
These results were robust in sensitivity analysis.

The investigators found meta-regression analysis showed that the factor (dose of pomegranate juice supplementation) was not associated with the treatment effects on FBG level [coefficient = -0.006, 95% CI = -0.023 to 0.011, p = 0.46].

The investigators found no significant difference in the FBG-lowering effect between trials that were conducted in subjects with cardiovascular disease risk [WMD = 0.30 mg/dL, 95% CI = -2.36 to 2.97, p = 0.82] and those that were conducted in healthy individuals [WMD = -2.53 mg/dL, 95% CI = -6.36 to 1.30, p = 0.19].

The investigators found no statistically significant differences in the pooled effects of pomegranate on FBG in the subgroups stratified by study designs, intervention durations, types of intervention, baseline BMI and baseline FBG levels (FBG levels at the beginning of the studie).

The investigators concluded pomegranate supplements have no favourable effect on improvements in glucose and insulin metabolism. The current evidence suggests that daily pomegranate supplementation is not recommended as a potential therapeutic strategy in glycemic management. Further large-scale RCTs with longer duration are required to confirm these results.

Original title:
Lack of efficacy of pomegranate supplementation for glucose management, insulin levels and sensitivity: evidence from a systematic review and meta-analysis by Huang H, Liao D, […], Zhu Y.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629805/

Additional information of El Mondo:
Find more information/studies on fruit consumption and diabetes right here.
 

Objectives:
Whether iron is associated with the development of gestational diabetes mellitus (GDM) is not clear. Therefore, this review article (meta-analysis) has been conducted.

Do increased dietary intake of iron and body iron status increase risk of gestational diabetes mellitus in pregnant women? 

Study design:
This review article included 12 case-control  studies, 9 cohort studies and  2  randomized  controlled  studies (RCT) with in total, 3,034 gestational diabetes mellitus pregnant women and 26,344 non-gestational diabetes mellitus pregnant women.

Results and conclusions:
The investigators found high dietary intake of heme iron was significantly associated with a 65% gestational diabetes mellitus risk [RR = 1.65, 95% CI = 1.28 to 2.12, I2 = 0%].

The investigators found for each 1 mg/day increment of dietary heme iron intake a significantly 38% gestational diabetes mellitus risk [RR = 1.38, 95% CI = 1.19 to 1.61, I2 = 0%].

The investigators found higher body iron stores, as represented by serum ferritin level, were correlated with a significantly increased gestational diabetes mellitus risk of 64% [RR = 1.64, 95% CI = 1.27 to 2.11, I2% = 7%].

The investigators found no association between gestational diabetes mellitus and the intakes of nonheme iron, total iron or supplemental iron.

The investigators concluded increased dietary intake of heme iron (at least 1 mg/day) and body iron status are positively associated with the risk of gestational diabetes mellitus development in pregnant women. Future studies are warranted to better understand the role of iron in gestational diabetes mellitus development.

Original title:
Dietary intake of heme iron and body iron status are associated with the risk of gestational diabetes mellitus: a systematic review and meta-analysis by Zhao L, Lian J, [...], Wang F.

Link:
http://apjcn.nhri.org.tw/server/APJCN/26/6/1092.pdf

Additional information of El Mondo:
Find more information/studies on iron, pregnancy and review article/significant/95% CI right here.

Gestational diabetes mellitus is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes mellitus affects between 2% and 5% of pregnant women.

Objectives:
Do patients with type 2 diabetes benefit from a low carbohydrate diet?

Study design:
This review article included a total of 9 RCTs with 734 patients with type 2 diabetes.

Results and conclusions:
The investigators found that low carbohydrate diet significantly reduced HbA1c level [WMD = -0.44, 95% CI = -0.61 to -0.26, p= 0.00] of patients with type 2 diabetes.

The investigators found that low carbohydrate diet significantly reduced triglycerides concentration [WMD = -0.33, 95% CI = -0.45 to -0.21, p = 0.00] of patients with type 2 diabetes.

The investigators found that low carbohydrate diet significantly increased HDL cholesterol concentration (WMD = 0.07, 95% CI = 0.03 to 0.11, p = 0.00] of patients with type 2 diabetes.

The investigators found that low carbohydrate diet was not associated with decreased level of total cholesterol and LDL cholesterol.

The investigators found subgroup analyses showed that short term intervention of low carbohydrate diet was effective for weight loss [WMD = -1.18, 95% CI = -2.32 to -0.04, p = 0.04] in patients with type 2 diabetes.

The investigators concluded there is a beneficial effect of low carbohydrate diet intervention on glucose control in patients with type 2 diabetes. The low carbohydrate diet intervention also has a positive effect on triglycerides and HDL cholesterol concentrations, but without significant effect on long term weight loss.

Original title:
Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: A systematic review and meta-analysis of randomized controlled trials by Meng Y, Bai H, […], Chen L.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28750216

Additional information of El Mondo:
Find more information/studies on carbohydrates and diabetes right here.

A low carbohydrate diet is a diet that is largely made up of meals/products with 20-40 En% carbohydrate. Practically, this means that all meals/products that you eat on a daily basis should on average contain 20-40 En% carbohydrate.
20-40 En% carbohydrate means that the total amounts of carbohydrate make up for a 20-40% of the total kcal of the diet. Check here which products contain 20-40 En% carbohydrate.

Objectives:
Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation. Therefore, this review article (meta-analysis) has been conducted.

Does alpha-linolenic acid dietary intake reduce diabetes risk?

Study design:
This review article included a total of 8 RCTs involving 212 participants with type 2 diabetes.
5 trials (62.5%) were parallel designs and 3 (37.5%) were crossover designs.
Participants were generally middle-aged (median age  =  54 years, range  =  47-64 years) and overweight or obese (median BMI  =  30.7, range  =  28.0-33.2).
Overall, participants had controlled diabetes (median HbA1c = 6.8%, median FBG = 7.95 mmol/L) and the majority of studies indicated the use of hypoglycemic drugs or other medications, although all studies excluded the use of insulin therapy.
The dose of ALA ranged from 1.5 to 7.4 g/day with a median assigned dose of 4.4, 5.4 and 5.4 g/day of ALA for trials that reported HbA1c, FBG and FBI, respectively.
The median duration of the treatment was 3 months, ranging from 2 to 12 months.
7 studies (87.5%) were considered high quality (MQS ≥8).

Results and conclusions:
The investigators found compared to a control diet, a median dose of 4.4 g/day of alpha-linolenic acid intake for a median duration of 3 months did not affect HbA1c (%) of patients with type 2 diabetes [MD =  -0.01, 95% = -0.32 to 0.31, p  =  0.96].

The investigators found compared to a control diet, a median alpha-linolenic acid dose of 5.4 g/day did not lower fasting blood glucose (FBG) of patients with type 2 diabetes [MD  = 0 .07, 95% CI = -0.61 to 0.76, p  = 0 .84] or fasting blood insulin (FBI) of patients with type 2 diabetes [MD  =  7.03, 95% CI = -5.84 to 19.89, p  = 0 .28].

The investigators found summary effect estimates were generally compromised by considerable and unexplained heterogeneity [I2 ≥ 75%].

The investigators found in the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA.

The investigators found further adjustment for publication bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of 0.25 [95% CI = -0.38 to -0.12, 0.001) for HbA1c (%).

The investigators concluded alpha-linolenic acid-enriched diet with a median alpha-linolenic acid dose of 4.4 g/day during 3 months has no effects on HbA1c, FBG or FBI in patients with type 2 diabetes. The scarce number of existing RCTs and the presence of heterogeneity in the meta-analysis limit the ability to make firm conclusions about alpha-linolenic acid in type 2 diabetes management. The potential for alpha-linolenic acid to have dose-dependent effects warrants further research in this area.

Original title:
The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials by Jovanovski E1, Li D, […], Vuksan V.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457843/

Additional information of El Mondo:
Find more information/studies on PUFA and diabetes right here.

4.4 g/day alpha-linolenic acid can be achieved by taking 1 to 2 tablespoons of flax or salba-chia seeds or about 12 whole walnuts per day.

 

Objectives:
The association between vitamin D deficiency and early spontaneous pregnancy loss (SPL) is unclear. Therefore, this review article (meta-analysis) has been conducted.

Does a vitamin D deficiency increase risk of early spontaneous pregnancy loss?

Study design:
This review article included 5 studies (case-control and cohort studies), including 10,630 pregnant women.

Results and conclusions:
The investigators found no significant association between a low 25(OH)D level (vitamin D level in blood) and an increased risk of early spontaneous pregnancy loss.

However, the investigators found in subgroup analysis, an extremely low 25(OH)D level (20 ng/mL) was significantly associated with an 124% increased risk of early spontaneous pregnancy loss in the first trimester [relative risk = 2.24, 95% CI = 1.15-4.37, I2 = 0.0%, p = 0.355].

The investigators concluded that severe vitamin D deficiency (20 ng/mL) could be detrimental to early embryonic development and increases risk of early spontaneous pregnancy loss.

Original title:
Meta-analysis of the effect of the maternal vitamin D level on the risk of spontaneous pregnancy loss by Zhang H, Huang Z, [...], Wei Y.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28500757

Additional information of El Mondo:
Find more information/studies on vitamin D, pregnancy and review article/significant/95% CI right here.

Objectives:
Are there differences in serum ceruloplasmin levels between patients with preeclampsia and healthy controls?

Study design:
This review article included 15 studies, with a total number of 1927 women.

Results and conclusions:
The investigators found that maternal serum ceruloplasmin concentration was significantly higher in preeclamptic than in the healthy pregnant women [MD = 12.57 mg/dL, 95% CI = 8.81 to 16.33].

The investigators found that ceruloplasmin levels were significantly higher both in mild [MD = 13.8 mg/dL, 95% CI = 2.64 to 23.53] and severe [MD = 21.84 mg/dL, 95% CI = 0.97 to 42.71] preeclampsia, when compared to the control group.

The investigators found that the severity of the disease did not significantly affect the levels of protein [MD = -9.34 mg/dL, 95% CI = -20.93 to 2.26].

The investigators concluded that serum ceruloplasmin may be a useful screening and follow-up tool for the evaluation of pregnant women with an indicative history of developing preeclampsia. Future studies are needed to evaluate the levels of this specific protein throughout the pregnancy course and provide data on its sensitivity and specificity by introducing cut-off values.

Original title:
Serum ceruloplasmin levels in preeclampsia: a meta-analysis by Bellos I, Papantoniou N and Pergialiotis V.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28605950

Additional information of El Mondo:
Find more information/studies on copper, pregnancy and review article/significant/95% CI right here.

Ceruloplasmin carries 65% to 90% of the copper found in blood.

Objectives:
It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. Therefore, this meta-analysis (systematic review) has been conducted.

Do probiotics supplements improve clinical outcomes in type 2 diabetic patients?

Study design:
This review article included 12 RCTs involving 684 type 2 diabetic patients.

Results and conclusions:
The investigators found a significant decreased glucose level in the probiotics group [pooled standardized mean difference = -0.18 mg/dL, 95% CI = -0.35 to -0.01, p = 0.04, I2 = 64%, p = 0.004] compared to the control group.

The investigators found a significant reduction in HbA1c in the probiotics group [pooled standardized mean difference = -0.38%, 95% CI = -0.62 to -0.14, p = 0.002, I2 = 0%, p = 0.72] compared to the control group.

The investigators found a significant reduction in fasting insulin level in the probiotics group [pooled standardized mean difference = -0.38, 95% CI = -0.59 to -0.18, p = 0.003, I2 = 0%, p = 0.81] compared to the control group.

The investigators found a significant reduced HOMA-IR level in the probiotics group [pooled standardized mean difference = -0.99, 95% CI = -1.52 to -0.4, p = 0.0002, I2 = 86%, p 0.00001] compared to the control group.

The investigators found a significant reduced CRP level in the probiotics group [pooled standardized mean difference = -1.34 mg/L, 95% CI = -1.76 to -0.92, p 0.00001, I2 = 90%, p 0.00001] compared to the control group.

The investigators found a non-significant reduction in both triglyceride levels [SMD = -0.23, 95% CI = -0.48 to 0.02, p = 0.07, I2 = 52%, p = 0.03] and cholesterol levels [total cholesterol: SMD = -0.18, 95% CI = -0.42 to 0.06, p = 0.14, I2 = 47%, p = 0.05 and LDL-cholesterol: SMD = -0.03, 95% CI = -0.20 to 0.14, p = 0.73, I2 = 3%, p = 0.41] in the probiotics group compared to the control group.

The investigators concluded that probiotics supplementation is associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. These results may provide evidence for encouraging use of probiotics in patients with type 2 diabetes mellitus. However, more randomized placebo-controlled trials with larger sample sizes are warranted to confirm these findings.

Original title:
Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials by Yao K, Zeng L, [...], Zou X.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491138/

Additional information of El Mondo:
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Objectives:
Epidemiological studies evaluating the associations between serum copper and ratios of copper/zinc (Cu/Zn) and the preeclampsia (PE) risk in Asian population have produced inconsistent results. Therefore, this review article (meta-analysis) has been conducted.

Do a higher serum copper and ratios of Cu/Zn increase the preeclampsia risk in Asian population?

Study design:
This review article included relevant studies up to November 2016.
Pooled standardized mean difference (SMD) was calculated with random effects model.

Results and conclusions:
The investigators found that preeclampsia patients significantly had a higher serum copper level [SMD = 1.05, 95% CI = 0.34 to 1.77, I2 = 96.9%, p 0.0001] compared with healthy pregnancy controls.

The investigators found in subgroup analyses, a higher serum copper level in preeclampsia patients was observed in case-control studies [SMD = 1.39, 95% CI = 0.44 to 2.34]. However, no significant difference was found between preeclampsia patients and healthy pregnancy controls for ratios of Cu/Zn [SMD = 0.26, 95% CI = -0.77 to 1.29, I2 = 95.8%, p 0.0001].

The investigators concluded that a higher serum copper level is associated with an increased risk of preeclampsia in Asian population. However, further studies are needed to confirm these results.

Original title:
High serum copper level is associated with an increased risk of preeclampsia in Asians: A meta-analysis by Song X, Li B, [...], Zhang D.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28385285

Additional information of El Mondo:
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Objectives:
Zinc sulfate may be a promising approach to treat neonatal jaundice. However, the results remain controversial. Therefore, this review article (meta-analysis) has been conducted.

Does zinc sulfate supplementation reduce neonatal jaundice?

Study design:
This review article included 5 RCTs involving 645 patients.

Results and conclusions:
The investigators found overall, compared with placebo, zinc sulfate supplementation failed to significantly reduce total serum bilirubin on 3 days [mean difference = 0.09 mg/dL, 95% CI = -0.49 to 0.67, p = 0.77]. Non-significant because p-value of 0.77 was greater than p-value of 0.05.

The investigators found overall, compared with placebo, zinc sulfate supplementation failed to significantly reduce total serum bilirubin on 7 days [mean difference= -0.37 mg/dL, 95% CI= -98 to 0.25, p  = 0.25].

The investigators found overall, compared with placebo, zinc sulfate supplementation failed to significantly reduce the incidence of hyperbilirubinemia [OR = 1.14, 95% CI = 0.74 to 1.76, p = 0.56].

The investigators found overall, compared with placebo, zinc sulfate supplementation showed no influence on phototherapy requirement [OR = 0.90, 95% CI = 0.41 to 1.98, p = 0.79]. Non-significant because OR of 1 was found in the OR of 0.41 to 1.98. OR of 1 means no risk/association.

The investigators found overall, compared with placebo, zinc sulfate supplementation significantly decreased duration of phototherapy [mean difference = -16.69 h, 95% CI = -25.09 to -8.3 h, p 0.000].

The investigators concluded zinc sulphate supplementation does not reduce the total serum bilirubin on 3 days and 7 days, the incidence of hyperbilirubinemia and phototherapy requirement, but significantly decreases duration of phototherapy.

Original title:
The influence of zinc sulfate on neonatal jaundice: a systematic review and meta-analysis by Yang L, Wu, [...], Tang J.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28372469

Additional information of El Mondo:
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Neonatal jaundice occurs when a baby has a high level of bilirubin in the blood. Bilirubin is a yellow substance that the body creates when it replaces old red blood cells. The liver helps break down the substance so it can be removed from the body in the stool.

A high level of bilirubin makes a baby's skin and whites of the eyes look yellow. This is called neonatal jaundice.

Jaundice is a common and usually harmless condition in newborn babies.
The symptoms of neonatal jaundice usually develop 2 to 3 days after the birth and tend to get better without treatment by the time the baby is about 2 weeks old.

Objectives:
Does diabetes increase risk of incident dementia and mild cognitive impairment?

Study design:
This review article included 19 prospective longitudinal studies including 6184 subjects with diabetes and 38530 subjects without diabetes. All subjects were without dementia or mild cognitive impairment at baseline (=at the beginning of the study).

There was no publication bias.

Results and conclusions:
The investigators found persons with diabetes had a significant increased risk of 46% for Alzheimer's disease [RR = 1.46, 95% CI = 1.20-1.77]. Significant means that there is an association with a 95% confidence.

The investigators found persons with diabetes had a significant increased risk of 148% for vascular dementia [RR = 2.48, 95% CI = 2.08-2.96].

The investigators found persons with diabetes had a significant increased risk of 51% for any dementia [RR = 1.51, 95% CI = 1.31-1.74]. Significant because RR of 1 was not found in the 95% CI of 1.31 to 1.74. RR of 1 means no risk/association.

The investigators found persons with diabetes had a significant increased risk of 21% for mild cognitive impairment [RR = 1.21, 95% CI = 1.02-1.45].

The investigators concluded diabetes is a risk factor for incident dementia (including Alzheimer's disease, vascular dementia and any dementia) and mild cognitive impairment.

Original title:
Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies by Cheng G, Huang G, [...], Wang H.

Link:
http://onlinelibrary.wiley.com/doi/10.1111/j.1445-5994.2012.02758.x/epdf

Additional information of El Mondo:
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Objectives:
Previous meta-analyses identified an inverse association of coffee consumption with the risk of type 2 diabetes. However, an updated meta-analysis is needed because new studies comparing the trends of association for caffeinated and decaffeinated coffee have since been published. Therefore, this review article has been conducted.

Does coffee intake reduce type 2 diabetes risk in a dose-response manner?

Study design:
This review article included 28 prospective cohort studies with 1109272 study participants and 45335 cases of type 2 diabetes. The follow-up duration ranged from 10 months to 20 years.

Results and conclusions:
The investigators found for compared with no or rare coffee consumption, a significant reduced risk of type 2 diabetes of:
8% [RR = 0.92, 95% CI = 0.90-0.94] for 1 cup/day;
15% [RR= 0.85, 95% CI = 0.82-0.88] for 2 cups/day;
21% [RR = 0.79, 95% CI = 0.75-0.83] for 3 cups/day;
25% [RR = 0.75, 95% CI = 0.71-0.80] for 4 cups/day;
29% [RR = 0.71, 95% CI = 0.65-0.76] for 5 cups/day and;
33% [RR = 0.67, 95% CI = 0.61-0.74] for 6 cups/day.

The investigators found a significant decreased risk of type 2 diabetes of 9% [RR = 0.91, 95% CI = 0.89-0.94] for an increasement of 1 cup/day caffeinated coffee and 6% [RR = 0.94, 95% CI = 0.91-0.98] for an increasement of 1 cup/day decaffeinated coffee [p for difference = 0.17].

The investigators concluded coffee consumption is inversely associated with the risk of type 2 diabetes in a dose-response manner. Both caffeinated and decaffeinated coffee is associated with reduced diabetes risk.

Original title:
Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis by Ding M, Bhupathiraju SN, […], Hu FB.

Link:
http://www.ncbi.nlm.nih.gov/pubmed/24459154

Additional information of El Mondo:
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Objectives:
The prevalence of obesity and diabetes is increasing among children, adolescents and adults. Although estimates of the efficacy of exercise training on fasting insulin and insulin resistance have been provided for adults, similar estimates have not been provided for youth. Therefore, this review article has been conducted.

Study design:
This review article included 24 trials.

Results and conclusions:
The investigators found a small to moderate effect for exercise training on fasting insulin and improving insulin resistance in youth [Hedges’ d effect size = 0.48, 95% CI = 0.22-0.74, p 0.001 and 0.31, 95% CI = 0.06-0.56, p 0.05, respectively].

The investigators concluded there is evidence to support the use of exercise training in the prevention and treatment of type 2 diabetes in youth.

Original title:
Exercise and Insulin Resistance in Youth: A Meta-Analysis by Fedewa MV, Gist NH, […], Dishman RK.

Link:
http://www.pediatricsdigest.mobi/content/133/1/e163.abstract

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Objectives:
Reported associations between protein intake from different sources and type 2 diabetes (T2D) have been inconsistent.Therefore, this review article has been conducted.

Study design:
This review article included 11 prospective cohort studies with 505,624 participants and 37,918 type 2 diabetes cases (follow-up range: 5-24 years).

Results and conclusions:
The investigators found for the comparison of the highest with lowest categories of total protein intakes a significant higher risk of 9% for type 2 diabetes [RR = 1.09, 95% CI = 1.06 to 1.13]. Significant means that there is an association with a 95% confidence.

The investigators found for the comparison of the highest with lowest categories of animal protein intakes a significant higher risk of 19% for type 2 diabetes [RR = 1.19, 95% CI = 1.11 to 1.28].

The investigators found for the comparison of the highest with lowest categories of plant protein intakes a non-significant reduced risk of 5% for type 2 diabetes [RR = 0.95, 95% CI = 0.89 to 1.02]. Non-significant means it cannot be said with a 95% confidence that a daily higher intake of plant protein really reduced risk of type 2 diabetes with 5%.

The investigators found for the comparison of the highest with lowest categories of plant protein intakes a significant reduced risk of 7% for type 2 diabetes among women [RR = 0.93, 95% CI = 0.85 to 1.00].

The investigators found for the comparison of the highest with lowest categories of plant protein intakes a significant reduced risk of 9% for type 2 diabetes among US populations [RR = 0.91, 95% CI = 0.84 to 0.97].

The investigators concluded that a higher intake of total and animal protein are both associated with an increased risk of of type 2 diabetes. However, a higher intake of plant protein decreases risk of type 2 diabetes among women and US populations.

Original title:
Dietary protein intake and risk of type 2 diabetes: results from the Melbourne Collaborative Cohort Study and a meta-analysis of prospective studies by Shang X, Scott D, […], Sanders KM.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/27629053

Additional information of El Mondo:
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Objectives:
Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies. However, studies reporting hypoglycemic effects of garlic in humans are conflicting. Therefore, this review article (meta-analysis) has been conducted.

Has garlic supplementation lowering effects on glycemic control measurements such as fasting blood glucose (FBG), postprandial glucose (PPG) and glycated haemoglobin (HbA1c)?

Study design:
This review article included a total of 7 RCTs (parallel design) that involved 9 comparisons with 513 subjects. The trials varied in size from 33 to 180 subjects. The study duration varied from 4 to 24 week (median: 12 week). The trials enrolled male and female subjects, both healthy and with diabetes.

Doses of garlic in the treatment group ranged from 600 to 1500 mg/d.

Results and conclusions:
The investigators found pooled analyses showed that garlic supplementation resulted in a statistically significant lowering in fasting blood glucose [SMD = -1.67, 95% CI = -2.80 to -0.55, p = 0.004].

The investigators could not perform a pooled analyse for postprandial glucose (PPG) control and glycosylated haemoglobin (HbA1c) outcomes, because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables.

The investigators concluded that garlic supplementation (600 to 1500 mg/d) during 12 weeks results in a lowering in fasting blood glucose. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

Original title:
Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials by Hou LQ, Liu YH and Zhang YY.

Link:
http://apjcn.nhri.org.tw/server/APJCN/24/4/575.pdf

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Objectives:
What is the relationship between intake of 12 major food groups and risk of type 2 diabetes (T2D)?

Study design:
This review article included prospective cohort studies.
The 12 major food groups are whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat and sugar-sweetened beverages (SSB).

The meta-evidence was graded "low" for legumes and nuts; "moderate" for refined grains, vegetables, fruit, eggs, dairy and fish; and "high" for processed meat, red meat, whole grains and sugar-sweetened beverages.

Results and conclusions:
The investigators found 6 out of the 12 food-groups showed a significant relation with risk of type 2 diabetes; 3 of them a decrease of risk with increasing consumption (whole grains, fruits and dairy) and 3 an increase of risk with increasing consumption (red meat, processed meat and sugar-sweetened beverages) in the linear dose-response meta-analysis.

The investigators found evidence of a non-linear relationship between fruits, vegetables, processed meat, whole grains and sugar-sweetened beverages and type 2 diabetes risk.

The investigators found optimal consumption of risk-decreasing foods resulted in a 42% reduction and consumption of risk-increasing foods was associated with a threefold type 2 diabetes risk, compared to non-consumption.

The meta-evidence was graded "low" for legumes and nuts; "moderate" for refined grains, vegetables, fruit, eggs, dairy and fish; and "high" for processed meat, red meat, whole grains, and sugar-sweetened beverages. Among the investigated food groups, selecting specific optimal intakes can lead to a considerable change in risk of type 2 diabetes.

The investigators concluded that a higher consumption of whole grains, fruits and dairy products reduces type 2 diabetes risk, while a higher consumption of red meat, processed meat and sugar-sweetened beverages increases type 2 diabetes risk.

Original title:
Food groups and risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies by Schwingshackl L, Hoffmann G, […], Boeing H.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28397016

Additional information of El Mondo:
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Objectives:
Olive oil (OO) as food is composed mainly of fatty acids and bioactive compounds depending from the extraction method. Both had been discussed as health promoting with still open questions. Therefore, this meta-analysis (systematic review) has been conducted.

Does olive oil intake reduce risk of type 2 diabetes?

Study design:
This review article included 4 cohort studies including 15,784 type 2 diabetes cases and 29 intervention trials.

Results and conclusions:
The investigators found the highest olive oil intake category showed a 16% reduced risk of type 2 diabetes [RR = 0.84, 95% CI = 0.77, 0.92) compared with the lowest. The reduced risk was significant.

The investigators found evidence for a nonlinear relationship between olive oil intake and the reduced risk of type 2 diabetes.

The investigators found in patients with type 2 diabetes that olive oil supplementation resulted in a significantly more pronounced reduction in HbA1c [MD = -0.27%, 95% CI = -0.37 to -0.17] and fasting plasma glucose [MD = -0.44 mmol/L, 95% CI = -0.66 to -0.22] as compared with the control groups.

The investigators concluded that the intake of olive oil is beneficial for the prevention and management of type 2 diabetes. This conclusion regards olive oil as food and might not been valid for single components comprising this food.

Original title:
Olive oil in the prevention and management of type 2 diabetes mellitus: a systematic review and meta-analysis of cohort studies and intervention trials by Schwingshackl L, Lampousi AM, […], Boeing H1.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28394365

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Objectives:
Does iron supplementation during pregnancy improve maternal haematological status and birth weight?

Study design:
This review article included 48 RCTs (17,793 women) and 44 cohort studies (1,851,682 women).

The dose of iron in RCTs ranged from 10 mg to 240 mg daily. Duration of supplementation varied from 7 to 8 weeks up to 30 weeks during pregnancy.

Significant heterogeneity existed for several outcomes that could not be explained substantially by pre-specified subgroups.

Results and conclusions:
The investigators found iron supplementation during pregnancy increased maternal mean haemoglobin concentration by 4.59 g/L [95% CI = 3.72 to 5.46] compared with controls.

The investigators found iron with folic acid was associated with a significant increase in mean haemoglobin concentration of 10.41 g/L [95% CI = 5.36 to 15.46, I2 = 0%, 9 trials] and reduction in risk of anaemia in the third trimester or at delivery of 56% [95% CI = 0.37 to 0.53, I2 = 44%, 5 trials]. Significant means there is an association with a 95% confidence.

The investigators found iron supplementation during pregnancy significantly reduced the risk of anaemia with 50% [95% CI = 0.42 to 0.59] compared with controls.

The investigators found iron supplementation during pregnancy significantly reduced the risk of iron deficiency (of the mother) with 41% [95% CI = 0.46 to 0.79] compared with controls.

The investigators found iron supplementation during pregnancy significantly reduced the risk of iron deficiency anaemia with 60% [95% CI = 0.26 to 0.60] compared with controls.

The investigators found iron supplementation during pregnancy significantly reduced the risk of low birth weight (2500 g) with 19% [95% CI = 0.71 to 0.93] compared with controls.

However, the investigators found iron supplementation during pregnancy non-significantly reduced the risk of preterm birth with 16% [95% CI = 0.68 to 1.03] compared with controls. Non-significant means there is no association with a 95% confidence.

The investigators found in cohort studies that anaemia in the first or second trimester was significantly associated with a higher risk for low birth weight of 29% [adjusted odds ratio 1.29, 95% CI = 1.09 to 1.53] and preterm birth with 21% [adjusted odds ratio = 1.21, 95% CI = 1.13 to 1.30].

The investigators found in exposure-response analysis that for every 10 mg increase in iron dose/day, up to 66 mg/day, the relative risk of maternal anaemia was significantly 0.88 [95% CI = 0.84 to 0.92, p for linear trend 0.001].

The investigators found in exposure-response analysis that birth weight increased by 15.1 g [95% CI = 6.0 to 24.2, p for linear trend = 0.005] and risk of low birth weight significantly decreased by 3% [relative risk = 0.97, 95% CI = 0.95 to 0.98, p for linear trend 0.001] every 10 mg increase in dose/day.

Furthermore, the investigators found for each 1 g/L increase in mean haemoglobin, birth weight increased by 14.0 g [95% CI = 6.8 to 21.8, p for linear trend = 0.002]. However, mean haemoglobin was not associated with the risk of low birth weight and preterm birth.

The investigators found no evidence of a significant effect on duration of gestation, small for gestational age births and birth length and duration of iron use was not significantly associated with the outcomes after adjustment for dose.

The investigators concluded daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight and a linear decrease in maternal anaemia with higher doses of iron, up to 66 mg/day.

Original title:
Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis by Haider BA, Olofin I, […], Fawzi WW.

Link:
http://www.bmj.com/content/346/bmj.f3443

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Iron deficiency anaemia occurs when there isn't enough iron in the body. Anaemia is a condition where the amount of haemoglobin in the blood is below the normal level.
Iron deficiency anaemia has been defined as haemoglobin 110 g/L and serum ferritin 12 µg/L.