Nutrition and health

Objectives:
Leg cramps are one of the common symptoms during pregnancy. About 30%-50% of pregnant women experience leg cramps twice a week. Leg cramps may cause severe pain and sleep disturbance, hinder performance of daily activities and may lengthen the duration of pregnancy and the type of childbirth. Therefore, this review article has been conducted.

Does oral magnesium supplementation reduce leg cramps during pregnancy?

Study design:
This review article included 4 RCTs with a total of 332 pregnant women.

Results and conclusions:
The investigators found the frequency of leg cramps during pregnancy was not significantly decreased in the magnesium group compared to the control group (group without magnesium) [WMD = -0.47, 95% CI = -1.14 to 0.20, p = 0.167].

The investigators found oral magnesium supplementation did not significantly improved the recovery from leg cramps during pregnancy compared to the control group [OR = 0.47, 95% CI = 0.14 to 1.52, p = 0.207].

The investigators found oral magnesium supplementation had no significant side effects in the treatment group (group with magnesium) compared to the control group [OR = 1.82, 95% CI = 0.90 to 3.69, p = 0.094].

The investigators concluded that oral magnesium supplementation is not effective in the treatment of leg cramps during pregnancy.

Original title:
Effect of oral magnesium supplementation for relieving leg cramps during pregnancy: A meta-analysis of randomized controlled trials by Liu J, Song G, [...], Meng T.

Link:
https://pubmed.ncbi.nlm.nih.gov/34247796/

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Objectives:
The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus (GDM) have not been well established. Therefore, this review article has been conducted.

Does vitamin and mineral supplementation improve glycemic control (like, fasting plasma glucose, serum insulin, homeostasis model assessment-insulin resistance and homeostasis model of assessment for β cell function) and decrease risk of inflammation and oxidative stress in women with gestational diabetes mellitus?

Study design:
This review article included 12 RCTs with 698 patients.

Patients included were in the age range of 18-40 years and all reported gestational diabetes mellitus screening was conducted between 24 weeks and 28 weeks gestation.

All trials gave vitamin and mineral supplementation orally.

Types, doses, dose regimens and duration of vitamin and mineral supplementation were as follows: magnesium (100-250 mg), zinc (4-233 mg), selenium (200 μg), calcium (400-1000 mg) and vitamin E (400 IU) every day for 6 weeks, vitamin D (200-50000 IU) every day or every 2 or 3 weeks for 6 weeks. Magnesium, zinc, selenium, calcium, vitamin D or E was given separately or in different combinations: magnesium and vitamin E; zinc and vitamin E; calcium and vitamin D; magnesium, zinc, calcium and vitamin D.

All trials used placebo as control intervention.

Among the 12 trials, 8 were judged to be at low risk of bias and 4 as being at unclear risk of bias. Unclear risks were related to attrition bias and other bias.

No significant publication bias was found for the effect of vitamin and mineral supplementation on all 8 outcomes.

Results and conclusions:
The investigators found magnesium, zinc, selenium, calcium, vitamin D and E (alone or in combination) supplementation significantly improved glycemic control in women with gestational diabetes mellitus compared to those receiving placebos:
-fasting plasma glucose (FPG) [MD = - 9.02, 95% CI = -12.09 to -5.96, p   0.00001];
-serum insulin [MD = -4.33, 95% CI = -5.35 to -3.32, p  0.00001];
-homeostasis model assessment-insulin resistance (HOMA-IR) [MD = -1.34, 95% CI = -1.60 to -1.07, p  0.00001] and;
-homeostasis model of assessment for β cell function (HOMA-B) [MD = - 15.58, 95% CI = -23.70 to -7.46, p = 0.0002].
Significantly because the calculated p-value of 0.0002 was less than the p-value of 0.05.

The investigators found vitamin and mineral supplementation (magnesium, zinc, selenium, calcium, vitamin D and E (alone or in combination)) significantly decreased risk of inflammation and oxidative stress through decreasing high-sensitivity C-reactive protein (hs-CRP) [MD = -1.29, 95% CI = -1.82 to -0.76, p  0.00001], malondialdehyde (MDA) [MD = -0.71, 95% CI = -0.97 to -0.45, p  0.00001] and increasing total antioxidant capacity (TAC) [MD = 45.55, 95% CI = 22.02 to 69.08, p = 0.0001].

The investigators concluded that vitamin and mineral supplementation improves glycemic control and decreases risk of inflammation and oxidative stress in women with gestational diabetes mellitus.

Original title:
The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus by Li D, Cai Z, [...], Zhang J.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145819/

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Objectives:
Do high maternal or neonatal DHA and/or EPA levels increase offspring birth weight and weight in childhood?

Study design:
This review article included 27 RCTs with 6,408 infants and 14 observational studies.

Results and conclusions:
The investigators found in RCTs that >650 mg/day DHA and/or EPA supplementation significantly increased birth weight [MD = 87.5g, 95% CI = 52.3 to 122.6, n = 3,831 participants, moderate quality].

The investigators found in RCTs that >650 mg/day DHA and/or EPA supplementation significantly increased combined BMI and BMI z score at 5-10 years [SMD = 0.11, 95% CI = 0.04 to 0.18, n = 3,220 participant, moderate quality].

The investigators found results from the observational studies were generally inconsistent. High trans fatty acids levels during pregnancy seemed to be associated with lower birth weight.

The investigators concluded this review and meta-analysis support a relationship between high maternal or neonatal DHA and/or EPA levels and higher offspring birth weight and weight in childhood. More high-quality long-term studies are still needed.

Original title:
Systematic Literature Review and Meta-Analysis of the Relationship Between Polyunsaturated and Trans Fatty Acids During Pregnancy and Offspring Weight Development by Ren X, Vilhjálmsdóttir BL, […], Specht  IO.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027310/

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Objectives:
Does intake of folic acid during pregnancy reduce risk of offspring's autism spectrum disorders?

Study design:
This review article included 10 studies with 23 sub-studies (9,795 autism spectrum disorders cases).

Results and conclusions:
The investigators found folic acid supplementation during early pregnancy significantly reduced risk of offspring's autism spectrum disorders with 43% [OR = 0.57, 95% CI = 0.41 to 0.78].

The investigators found the consumption of a daily amount of at least 400 μg folic acid from dietary sources and supplements significantly reduced risk of offspring's autism spectrum disorders with 45% [OR = 0.55, 95% CI = 0.36 to 0.83].

The investigators concluded that the consumption of a daily amount of at least 400 μg (400 mcg) folic acid from dietary sources and supplements during pregnancy reduces risk of offspring's autism spectrum disorders.

Original title:
Prenatal Folic Acid Supplements and Offspring's Autism Spectrum Disorder: A Meta-analysis and Meta-regression by Liu X, Zou M, [...], Chen WX.

Link:
https://pubmed.ncbi.nlm.nih.gov/33743119/

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Objectives:
Does vitamin A supplementation reduce risk of bronchopulmonary dysplasia (BPD) in premature infants?

Study design:
This review article included 9 RCTs with 709 infants received vitamin A treatment (intervention group) and 700 infants did not receive vitamin A treatment (control group).
The dose of vitamin A regimens varied from 1500 to 10,000 IU (450 to 3,003 micrograms) and the treatment durations generally lasted for 4 weeks.

The funnel plots for all synthesized outcomes remained symmetrical, indicating that there was no significant publication bias.

Results and conclusions:
The investigators found when compared to the control group, vitamin A supplementation significantly reduced the incidence of bronchopulmonary dysplasia in premature infants with 33% [OR  =  0.67, 95% CI = 0.52 to 0.88].
The sensitivity analyses were performed by excluding single RCT one by one. The results of sensitivity analysis of all outcomes had indicated no substantial result changes among the overall estimates.

The investigators concluded that vitamin A supplementation is beneficial to reduce bronchopulmonary dysplasia in premature infants.  

Original title:
Vitamin A supplementation prevents the bronchopulmonary dysplasia in premature infants: A systematic review and meta-analysis by Ding Y, Chen Z and Lu Y.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837939/

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Bronchopulmonary dysplasia is a form of chronic lung disease that develops in preterm neonates treated with oxygen and positive-pressure ventilation.
 

Objectives:
Does a high dietary cholesterol intake increase risk of gestational diabetes mellitus?

Study design:
This review article included 3 cohort studies, 4 cross-sectional studies and 2 case-control studies involving 30,123 participants and 3,237 women with gestational diabetes mellitus (diabetes mellitus in pregnancy).

Results and conclusions:
The investigators found comparing highest versus lowest category of dietary cholesterol intake, that the highest dietary cholesterol intake significantly increased risk of gestational diabetes mellitus with 49% [pooled RR = 1.49, 95% CI = 1.18 to 1.88].

The investigators found in dose-response analysis that the risk of gestational diabetes mellitus significantly increased by 32% [RR = 1.32, 95% CI = 1.20 to 1.45] for every increase of 100 mg per day in dietary cholesterol intake.

The investigators concluded a high dietary cholesterol intake (at least 100 mg per day) increases risk of gestational diabetes mellitus.

Original title:
Dietary Cholesterol Intake and Risk of Gestational Diabetes Mellitus: A Meta-Analysis of Observational Studies by Gao F and Cui CY.

Link:
https://pubmed.ncbi.nlm.nih.gov/33416437/

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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

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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

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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:
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

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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

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

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

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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

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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:
Is supplementation of formula milk with LCPUFA (long-chain polyunsaturated fatty acids) both safe and beneficial for full-term infants, while focusing on effects on visual function, neurodevelopment and physical growth?

Study design:
This review article included 15 RCTs (n = 1889).
9 studies assessed visual acuity, 6 of which used visual evoked potentials (VEP), 2 Teller cards and 1 both. 4 studies reported beneficial effects and the remaining 5 did not.
GRADE analysis of the outcomes indicated that the overall quality of evidence was low.

Results and conclusions:
The investigators found a meta-analysis of 3 RCTs (n = 244) showed significant benefit for sweep VEP acuity at 12 months (log of the minimum angle of resolution) [MD = -0.15, 95% CI = -0.17 to -0.13, I2 = 0%, low-quality of evidence].
However, the meta-analysis of 3 other RCTs (n = 256) showed no benefit for visual acuity measured with Teller cards at 12 months (cycles/degree) [MD = -0.01, 95% CI = -0.12 to 0.11, I2 = 0%, low-quality of evidence].

The investigators found meta-analysis of 4 RCTs (n = 661) revealed no significant differences between LCPUFA and placebo groups in BSID Mental Developmental Index scores at 18 months [MD = 0.06, 95% CI = -2.01 to 2.14, I2 = 75%, low-quality of evidence] and no significant differences in BSID Psychomotor Development Index scores at 18 months [MD = 0.69, 95% CI = -0.78 to 2.16, I2 = 61%, low-quality of evidence].

There were also no significant differences between the two groups in BSID-II scores at one year and two years of age.

The investigators found meta-analysis of 5 RCTs (n = 521) showed that the supplemented group had lower weight (z scores) at one year of age [MD = -0.23, 95% CI = -0.40 to -0.06, I2 = 83%, low-quality of evidence] and that the two groups showed no significant differences with respect to length and head circumference (z scores).

The investigators found meta-analysis at 18 months and at two years revealed no significant differences between the two groups with respect to weight (kg), length (cm) and head circumference (cm).

The investigators concluded there are no beneficial effects or harms of LCPUFA supplementation on neurodevelopmental outcomes of formula-fed full-term infants and no consistent beneficial effects on visual acuity. Therefore, routine supplementation of full-term infant milk formula with LCPUFA cannot be recommended at this time.

Original title:
Long chain polyunsaturated fatty acid supplementation in infants born at term by Jasani B, Simmer K, […], Rao SC.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28281303

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Objectives:
Is a low maternal circulating 25 hydroxyvitamin D (25-OHD) associated with an increased risk of preterm birth or spontaneous preterm birth and can vitamin D supplementation alone during pregnancy reduce risk of preterm birth?

Study design:
This review article included 6 RCTs and 18 observational studies.

Results and conclusions:
The investigators found maternal circulating 25-OHD deficiency significantly increased risk of preterm birth with 25% [pooled OR = 1.25, 95% CI = 1.13-1.38]. However, maternal circulating 25-OHD insufficiency was not associated with an increased risk of preterm birth [pooled OR = 1.09, 95% CI = 0.89-1.35]. Not associated because OR of 1 was found in 95% CI of 0.89 to 1.35. OR of 1 means no risk/association.

The investigators found vitamin D supplementation alone during pregnancy significantly reduced risk of preterm birth with 43% [pooled RR = 0.57, 95% CI = 0.36-0.91]. Significantly because RR of 1 was not found in 95% CI of 0.36 to 0.91. RR of 1 means no risk/association.

The investigators found maternal circulating 25-OHD 50 nmol/L significantly increased risk of spontaneous preterm birth with 45% [pooled OR = 1.45, 95% CI = 1.20-1.75]. 

The investigators concluded a maternal circulating 25-OHD 50 nmol/L increases risk of spontaneous preterm birth and vitamin D supplementation alone during pregnancy reduces risk of preterm birth. However, extrapolation of the results must be done with caution and there is urgent need for larger, better-designed RCT to confirm this effect.

Original title:
Vitamin D and risk of preterm birth: Up-to-date meta-analysis of randomized controlled trials and observational studies by Zhou SS, Tao YH, […], Tao FB.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/28150405

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