CAT: based on OB PICO 2 

Clinical Scenario: As in the past, please briefly outline the scenario and state your clinical question as concisely and specifically as possible  

 KB is a 32 year old female with no past medical history who is 23 weeks pregnant with her first child. She states that her mother had gestational diabetes when she had her so is now concerned about her own pregnancy. She is overweight but states that she has been keeping a healthy diet, and wants to avoid any long term medication. She read online about how probiotics can help prevent gestational diabetes and asks for your advice.   

Search Question: Clearly state the question (including outcomes or criteria to be tracked) 

In pregnant females, what are the benefits of probiotics in preventing and reducing the risk of gestational diabetes?  

Question Type: What kind of question is this? (boxes now checkable in Word) 

  

☐Prevalence ☐Screening ☐Diagnosis 

☐Prognosis Treatment ☐Harms 

 

PICO Search Elements: 

P	I	C	O
females	Probiotics	No probiotics	Decrease progression to gestational diabetes
Females who are pregnant	Probiotic supplements	Standard treatment	Disease prevention
Females wanting to avoid long term medication	Dietary supplements	diet/medication	Reduce risk of gestational diabetes
Overweight females

 

 

Search Strategy: 

Cochrane Review	Science Direct	Google Scholar	Wiley Online	Springer Link
Search terms used	Search terms used	Search terms used	Search terms used	Search terms used
a. Gestational diabetes prevention: 35	a. Gestational diabetes prevention: 22,272	a. Gestational diabetes prevention: >300,000	a. Gestational diabetes prevention: 23,002	a. Gestational diabetes prevention: 11,780
b. Gestational diabetes prevention + probiotics: 24	b. Gestational diabetes prevention + probiotics: 1,333	b. Gestational diabetes prevention + probiotics: 10,008	b. Gestational diabetes prevention + probiotics: 846	b. Probiotics for gestational diabetes prevention: 512
c. Gestational diabetes prevention + probiotics + last 10 years: 22	c. Gestational diabetes prevention + probiotics + last 10 years + research articles: 107	c. Gestational diabetes prevention + probiotics + last 2 years: 3,021	c. Gestational diabetes prevention + probiotics + last 10 years + RCT: 89	c. Probiotics for gestational diabetes prevention + last 5 years: 203
Selection criteria	Selection criteria	Selection criteria	Selection criteria
Cochrane review is a great source to find meta-analysis and systematic reviews. The way I narrowed my search here was to only look at reviews that discussed the relationship between probiotics and GDM in the past 10 years.	Science Direct is one of my favorite databases to use. It always has a good mix of articles and chapters on the topics. I looked up research articles that were done in the past 10 years.	Google scholar is always the first place I go to when I am looking for a topic. It allows me to search a topic broadly and get inspired by some of the articles it shows. I narrowed the search to the past 2 years and still have over 3,000 articles. For this reason, I really use google scholar as a base to know what to search on other databeases rather then a source itself.	Wiley is also a great source to use. I started looking up just gestational diabetes prevention and found way too many, so then when I narrowed it to probiotics and in the past 10 years, I was able to come to a much smaller number.	This was a new search engine for me, but I thought it was very helpful. It had so many articles on the specific topic I was looking at and I was able to even narrow it done further by looking at probiotics for GDM prevention articles that were written in the past 5 years.

  

  

Articles Chosen At least 6 articles for Inclusion (please copy and paste the abstract with link): 

Please pay attention to whether the articles actually address your question and whether they are the highest level of evidence available. (Be aware that the instructor may also do a search and should not be able to find better articles that you overlooked).  
If after reviewing you cannot find high quality articles, be prepared to explain the extensiveness of your search and why there aren’t any better sources available. If you are having trouble finding better sources, please reach out to the librarian or one of the instructors for help with this.  

1. Probiotics for preventing gestational diabetes

Barrett  HL, Dekker Nitert  M, Conwell  LS, Callaway LK. Probiotics for preventing gestational diabetes.Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD009951. DOI: 10.1002/14651858.CD009951.pub2. Accessed 27 August 2021.  

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009951.pub2/full 

Abstract: 

Background 

Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. 

Objectives 

To assess the effects of probiotic supplementation when compared with other methods for the prevention of GDM. 

Search methods 

We searched the Cochrane Pregnancy and childbirth Group’s Trials Register (31 August 2013) and reference lists of the articles of retrieved studies. 

Selection criteria 

Randomised and cluster‐randomised trials comparing the use of probiotic supplementation with other methods for the prevention of the development of GDM. Cluster‐randomised trials were eligible for inclusion but none were identified. Quasi‐randomised and cross‐over design studies are not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results would also have been excluded. 

Data collection and analysis 

Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included study. Data were checked for accuracy. 

Main results 

Eleven reports (relating to five possible trials) were found. We included one study (six trial reports) involving 256 women. Four other studies are ongoing. 

The included trial consisted of three treatment arms: probiotic with dietary intervention, placebo and dietary intervention, and dietary intervention alone; it was at a low risk of bias. The study reported primary outcomes of a reduction in the rate of gestational diabetes mellitus (risk ratio (RR) 0.38, 95% confidence interval (CI) 0.20 to 0.70), with no statistical difference in the rates of miscarriage/intrauterine fetal death (IUFD)/stillbirth/neonatal death (RR 2.00, 95% CI 0.35 to 11.35). Secondary outcomes reported were a reduction in infant birthweight (mean difference (MD) ‐127.71 g, 95% CI ‐251.37 to ‐4.06) in the probiotic group and no clear evidence of increased risk of preterm delivery (RR 3.27, 95% CI 0.44 to 24.43), or caesarean section rate (RR 1.23, 95% CI 0.65 to 2.32). The primary infant outcomes of rates of macrosomia and large‐for‐gestational age infants were not reported. The following secondary outcomes were not reported: maternal gestational weight gain, pre‐eclampsia, and the long‐term diagnosis of diabetes mellitus; infant body composition, shoulder dystocia, admission to neonatal intensive care, jaundice, hypoglycaemia and long‐term rates of obesity and diabetes mellitus. 

Authors’ conclusions 

One trial has shown a reduction in the rate of GDM when women are randomised to probiotics early in pregnancy but more uncertain evidence of any effect on miscarriage/IUFD/stillbirth/neonatal death. There are no data on macrosomia. At this time, there are insufficient studies to perform a quantitative meta‐analysis. Further results are awaited from four ongoing studies. 

 

2. 2.Impactof Probiotics in Women with gestational diabetes mellitus on metabolic health: a randomized control trail.   

Karen L. Lindsay, Lorraine Brennan, Maria A. Kennelly, Orla C. Maguire, Thomas Smith, Sinead Curran, Mary Coffey, Michael E. Foley, Mensud Hatunic, Gergus Shanahan, Fionnuala M. McAuliffe , Impact of probiotics in women with gestational diabetes mellitus on metabolic  health: a randomized controlled trial, American Journal of Obstetrics and Gynecology, 

Volume 212, Issue 4, 2015 

https://www.sciencedirect.com/science/article/pii/S0002937815001301?casa_token=YJYS6QTP7AUAAAAA:SXB566TZBnBqs3VxahSsAPSm9juDsIHum67YetoS-n62mauzIdrJeu6_ef6RhgyTC9sNxDM43-A 

Abstract: 

Objective 

Probiotics are live microorganisms that may confer health benefits on the host. Recent trials of probiotic use among healthy pregnant women demonstrate potential for improved glycemic control. The aim of this study was to investigate the effects of a probiotic capsule intervention on maternal metabolic parameters and pregnancy outcome among women with gestational diabetes. 

Study Design 

This double-blind placebo-controlled randomized trial recruited pregnant women with a new diagnosis of gestational diabetes or impaired glucose tolerance following a 3-hour 100-g glucose tolerance test. Women were randomized to a daily probiotic (Lactobacillus salivarius UCC118) or placebo capsule from diagnosis until delivery. Fasting blood samples were collected at baseline and 4-6 weeks after capsule commencement for analysis of glucose, insulin, c-peptide, and lipids. The primary outcome was difference in fasting glucose postintervention, first analyzed on an intention-to-treat basis and followed by per-protocol analysis that excluded women commenced on pharmacological therapy (insulin or metformin). Secondary outcomes were changes in insulin, c-peptide, homeostasis model assessment and lipids, requirement for pharmacological therapy, and neonatal anthropometry. 

Results 

Of 149 women recruited and randomized, there were no differences between the probiotic and placebo groups in postintervention fasting glucose (4.65 ± 0.49 vs 4.65 ± 0.53 mmol/L; P = 373), requirement for pharmacological therapy (17% vs 14%; P = .643), or birthweight (3.57 ± 0.64 vs 3.60 ± 0.57 kg; P = .845). Among 100 women managed with diet and exercise alone, fasting plasma glucose decreased significantly within both the probiotic (4.76 ± 0.45 to 4.57 ± 0.42 mmol/L; P < .001) and placebo (4.85 ± 0.58 to 4.58 ± 0.45 mmol/L; P < .001) groups, but the levels between groups did not differ (P = .316). The late gestation-related rise in total and low-density lipoprotein (LDL) cholesterol was attenuated in the probiotic vs the placebo group (+0.27 ± 0.48 vs +0.50 ± 0.52 mmol/L total cholesterol, P = .031; +0.08 ± 0.51 vs +0.31 ± 0.45 mmol/L LDL cholesterol, P = .011). No differences were noted between groups in other metabolic parameters or pregnancy outcome. 

Conclusion 

A probiotic capsule intervention among women with abnormal glucose tolerance had no impact on glycemic control. The observed attenuation of the normal pregnancy-induced rise in total and LDL cholesterol following probiotic treatment requires further investigation, particularly in this obstetric group at risk of future metabolic syndrome. 

 

3. The effect of probiotic supplementation on the risk of gestational diabetes mellitus among high-risk pregnant women: A parallel double-blind, randomized, placebo-controlled clinical trial

 

Ali Shahriari, Elham Karimi, Mohammadali Shahriari, Neda Aslani, Maryam khooshideh, Arman Arab, 

The effect of probiotic supplementation on the risk of gestational diabetes mellitus among high-risk pregnant women: A parallel double-blind, randomized, placebo-controlled clinical trial, Biomedicine & Pharmacotherapy,Volume 141, 2021, 

 

The effect of probiotic supplementation on the risk of gestational diabetes mellitus among high-risk pregnant women: A parallel double-blind, randomized, placebo-controlled clinical trial – ScienceDirect (cuny.edu) 

 

Abstract: 

Background 

Based on a comprehensive search, we realized that the findings of the available literature are contradictory, and also limited data are available on Middle Eastern populations in terms of probiotic supplementation during the pregnancy. Therefore, the current double-blind, randomized, placebo-controlled clinical trial was carried out to investigate the effects of probiotic supplementation during pregnancy on the risk of gestational diabetes mellitus and also other maternal and neonatal outcomes. 

Materials and methods 

The pregnant women were randomized to either received probiotic supplement (n = 271) or placebo (n = 271) from the first half of the second trimester (14 weeks of pregnancy) up to 24 weeks when pregnant women routinely evaluated regarding the GDM. During the 24–28 weeks of pregnancy, mothers were evaluated regarding the presence of GDM using a 75 g oral glucose tolerance test (OGTT). The fasting blood glucose (FBG) was also evaluated within OGTT processes. Each 500 mg probiotic capsule was a mixture of Lactobacillus acidophilus LA1 (>7.5 × 109 CFU), Bifidobacterium longum sp54 cs (>1.5 × 109 CFU), and Bifidobacterium bifidum sp9 cs (>6 × 109 CFU). 

Results 

Overall, 507 pregnant women make up our study population with a mean age of 32.03 years and a Body Mass Index (BMI) of 30.20 kg/m2. There was no significant difference between the intervention and the control group regarding FBG (88.68 vs. 89.61 mg/dL; P = 0.338), OGTT-1h (163.86 vs. 166.88; mg/dL; P = 0.116), and OGTT-2h (138.39 vs. 139.27; mg/dL; P = 0.599). The incidence of GDM in the intervention group was 41.9% which was not significantly different from the control group (40.2%) (P = 0.780). Likewise, no significant difference was detected in terms of other studied parameters. 

Conclusions 

It seems that probiotics supplementation of pregnant women from the first half of the second trimester up to 24 weeks of pregnancy does not reduce the risk of GDM, or improve other neonatal and maternal outcomes. 

 

 

4. 4.Probiotics for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Women: FindingsFrom the SPRING Double-Blind Randomized Controlled Trial 

Callaway, Leonie K., et al. “Probiotics for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Women: Findings from the Spring Double-Blind Randomized Controlled Trial.” Diabetes Care, American Diabetes Association, 1 Mar. 2019, care.diabetesjournals.org/content/42/3/364.short. 

https://care.diabetesjournals.org/content/42/3/364.short 

Abstract: 

OBJECTIVE Given the role of gut microbiota in regulating metabolism, probiotics administered during pregnancy might prevent gestational diabetes mellitus (GDM). This question has not previously been studied in high-risk overweight and obese pregnant women. We aimed to determine whether probiotics (Lactobacillus rhamnosus and Bifidobacterium animalis subspecies lactis) administered from the second trimester in overweight and obese women prevent GDM as assessed by an oral glucose tolerance test (OGTT) at 28 weeks’ gestation. Secondary outcomes included maternal and neonatal complications, maternal blood pressure and BMI, and infant body composition. 

RESEARCH DESIGN AND METHODS This was a double-blind randomized controlled trial of probiotic versus placebo in overweight and obese pregnant women in Brisbane, Australia. 

RESULTS The study was completed in 411 women. GDM occurred in 12.3% (25 of 204) in the placebo arm and 18.4% (38 of 207) in the probiotics arm (P = 0.10). At OGTT, mean fasting glucose was higher in women randomized to probiotics (79.3 mg/dL) compared with placebo (77.5 mg/dL) (P = 0.049). One- and two-hour glucose measures were similar. Preeclampsia occurred in 9.2% of women randomized to probiotics compared with 4.9% in the placebo arm (P = 0.09). Excessive weight gain occurred in 32.5% of women in the probiotics arm (55 of 169) compared with 46% in the placebo arm (81 of 176) (P = 0.01). Rates of small for gestational age (<10th percentile) were 2.4% in the probiotics arm (5 of 205) and 6.5% in the placebo arm (13 of 199) (P = 0.042). There were no differences in other secondary outcomes. 

CONCLUSIONS The probiotics used in this study did not prevent GDM in overweight and obese pregnant women. 

 

5. TheEffects of Probiotic Supplementation on Genetic and Metabolic Profiles in Patients with Gestational Diabetes Mellitus: a Randomized, Double-Blind, Placebo-Controlled Trial 

 

Babadi, M., Khorshidi, A., Aghadavood, E. et al. The Effects of Probiotic Supplementation on Genetic and Metabolic Profiles in Patients with Gestational Diabetes Mellitus: a Randomized, Double-Blind, Placebo-Controlled Trial. Probiotics & Antimicro. Prot. 11, 1227–1235 (2019). https://doi-org.york.ezproxy.cuny.edu/10.1007/s12602-018-9490-z 

Abstract: 

This study was carried out to evaluate the effects of probiotic supplementation on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM) who were not on oral hypoglycemic agents. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 patients with GDM. Participants were randomly divided into two groups to intake either probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum (2 × 109 CFU/g each) (n = 24) or placebo (n = 24) for 6 weeks. Probiotic intake upregulated peroxisome proliferator-activated receptor gamma (P = 0.01), transforming growth factor beta (P = 0.002) and vascular endothelial growth factor (P = 0.006), and downregulated gene expression of tumor necrosis factor alpha (P = 0.03) in peripheral blood mononuclear cells of subjects with GDM. In addition, probiotic supplementation significantly decreased fasting plasma glucose (β, − 3.43 mg/dL; 95% CI, − 6.48, − 0.38; P = 0.02), serum insulin levels (β, − 2.29 μIU/mL; 95% CI, − 3.60, − 0.99; P = 0.001), and insulin resistance (β, − 0.67; 95% CI, − 1.05, − 0.29; P = 0.001) and significantly increased insulin sensitivity (β, 0.009; 95% CI, 0.004, 0.01; P = 0.001) compared with the placebo. Additionally, consuming probiotic significantly decreased triglycerides (P = 0.02), VLDL-cholesterol (P = 0.02), and total-/HDL-cholesterol ratio (P = 0.006) and significantly increased HDL-cholesterol levels (P = 0.03) compared with the placebo. Finally, probiotic administration led to a significant reduction in plasma malondialdehyde (P < 0.001), and a significant elevation in plasma nitric oxide (P = 0.01) and total antioxidant capacity (P = 0.01) was observed compared with the placebo. Overall, probiotic supplementation for 6 weeks to patients with GDM had beneficial effects on gene expression related to insulin and inflammation, glycemic control, few lipid profiles, inflammatory markers, and oxidative stress. 

 

6. Doprobiotics effectively ameliorate glycemic control during gestational diabetes? A systematic review 

 

Dallanora, S., Medeiros de Souza, Y., Deon, R.G. et al. Do probiotics effectively ameliorate glycemic control during gestational diabetes? A systematic review. Arch Gynecol Obstet 298, 477–485 (2018). https://doi-org.york.ezproxy.cuny.edu/10.1007/s00404-018-4809-2 

Abstract: 

Background 

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The aim of this work was to systematically review all studies in which probiotic supplements were used during pregnancy and analyse the effects on GDM. 

Methods 

The data were collected using the medical subheading (MeSH) terms: (“diabetes, gestational”[MeSH Terms] OR (“diabetes”[All Fields] AND “gestational”[All Fields]) OR “gestational diabetes”[All Fields] OR (“gestational”[All Fields] AND “diabetes”[All Fields])) AND (“probiotics”[MeSH Terms] OR “probiotics”[All Fields]). The search included original articles written in English/Portuguese and published between 2012 and 2017. 

Results 

Of the 31 articles identified, seven met the inclusion criteria and were included in this review. In these studies, the sample size ranged from 60 to 373 women with GDM, which was between 24 and 40 weeks of pregnancy (second and third trimesters). Results demonstrated that probiotics used during pregnancy in women with GDM may improve glycaemic control and reduce VDL cholesterol, triglycerides, and inflammatory markers. 

Conclusions 

The present systematic review highlights the importance of probiotics for glycemic control and decrease of inflammatory markers in GDM. Further long-term studies should be conducted to elucidate this interaction. 

 

FOR THE DRAFT & FINAL CAT (ROTATIONS 8 & 9) – YOU WILL INCLUDE THE PARTS ABOVE AND COMPLETE THE REMAINING PARTS BELOW: 

Summary of the Evidence: 

 

Randomised and cluster-randomised trials comparing the use of probiotic supplementation with other methods for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies are not eligible forinclusion in this review 

Author (Date)	Level of Evidence	Sample/Setting  (# of subjects/ studies, cohort definition etc. )	Outcome(s) studied	Key Findings	Limitations and Biases
1. Probiotics for preventing gestational diabetes  Barrett  HL, Dekker Nitert  M, Conwell  LS, Callaway LK  2021	Systtematic review	-They looked at randomized and cluster randomized trails  -quasi randomized trails were excluded  -they focused on one complete RCT that had 256 women who were followed for 12 months.	-Primary outcomes were: maternal GDM, infants who were large for gestational age and who had macrosomia, and those n which GDM lead to death.   -Minor outcomes were: mothers with preeclampsia and preterm and C-section deliveries. As well as infants with jaundice, shoulder dystocia and NICU admission.	-when started on Probiotics early in pregnancy, there is a high chance of reduction in the cases of GDM.   -There is no data on macrosomia or risk of miscarriage or still birth.	-one limitation is that they focused on one study rather then many, as you would normally see in a RCT.   -since this was a double blind study, they were able to thoroughly limit any biases in the results, as both the subject and experimenter were blind.   -since they looked at one study, there was not enough info present to assess the risk reduction of macrosomia, miscarriages or neonatal death.
2. Impact of Probiotics in Women with gestational diabetes mellitus on metabolic health: a randomized control trail.    Karen L. Lindsay, Lorraine Brennan, Maria A. Kennelly, Orla C.  2015	RCT-double blind	-149 pregnant women were enrolled with a new diagnosis of gestational diabetes.  -those were were eligible included those who were 18 years old and under 35 weeks pregnant, with a single pregnancy and were able to speak and understand English.	-primary outcome: the difference in postintervention maternal fasting glucose levels in those that were given the probiotic vs those that were given a placebo.   -other outcomes included metabolic parameters, gestational weight gain, HTN, delivery complications and neonatal outcomes.	-a probiotic capsule had no impact on the glycemic control in these pregnant women.  -there was no differences noted in neonatal outcomes  -subtle positive effects of probiotics were noted in the metabolic aspect, as those women taking the probiotic had a less total increase in total and LDL cholesterol compared to the placebo group.	-one limitation is that the sample size is small, and is unable to assess the effect of the probiotic fully.   -Also there was a 18% dropout in the patients since the start of this trail, this was mainly due to lack of follow up visits.   -since this was a double blind RCT, they were able to limit any possible bias.
3. The effect of probiotic supplementation on the risk of gestational diabetes mellitus among high-risk pregnant women: A parallel double-blind, randomized, placebo-controlled clinical trial    Ali Shahriari Et Al  2021	Double blind RCT	-507 pregnant women were enrolled, in which 271 were given a probiotic supplement and 271 were given a placebo for weeks 14-24 of their pregnancy.	-primary outcome included that overall effect of probiotic supplementation on the risk of gestational diabetes.   -secondary outcomes included neonatal effects such as abnormal growth, need to go to ICU etc. As well as maternal outcomes such as need for C-section, and risk of HTN etc.	-they found that probiotic supplementation of pregnant women, during the first half of their second trimester to the end of it (14-24 weeks) has no effect on the reduction of risk of GDM.  -probiotics did not seem to improve maternal or neonatal outcomes.	-since they only looked at the effect of probiotics for 14-24 weeks during the pregnancy, more studies will be needed that look at the effects of probiotics for a longer period of time.   -since thye only looked at the effect of one specific probiotic (with a mixture of Lactobacillis acidophilus, bifidobacterium longum, and bifidobacterium bifidum), more studies using other probiotics are needed.
4.. Probiotics for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Women: Findings From the SPRING Double-Blind Randomized Controlled Trial  Callaway, Leonie K., et al.  2019	Double blind RCT	-a total of 411 pregnant women completed this study, 204 were in the placebo group and 207 were in the probiotic group.	-Primary outcome looked at was the frequency of GDM in women 28 weeks pregnant (by a 75 OGTT).   -secondary outcomes included gestational weight gain, preeclampsia, hypertensive disorders, c-section, and gestational age at delivery.	-they found that supplementation with probiotics did not seem to prevent the risk of gestational diabetes in women who were obese or overweight.   -they found that there was a reduction in infants with SGA being born to women taking probiotics.   -it is possible, that if these probiotics were started prior to pregnancy or in early pregnancy there could have been a more positive outcome.	-one limitation is that they looked at women only in their second trimester, so the effects of probiotics given early on were not counted for.  -Also there was some slow recruitment, and some women were recruited after 20 week gestation, giving only a 4 week window of treatment, which is not enough to see a response.   -They also did not have regular OGTT testing in order to assess for subtle differences throughout the study
5. The Effects of Probiotic Supplementation on Genetic and Metabolic Profiles in Patients with Gestational Diabetes Mellitus: a Randomized, Double-Blind, Placebo-Controlled Trial  Babadi, M., Khorshidi, A., Aghadavood, E. et al.  2019	Double Blind RCT	-48 women who were diagnosed with GDM at 24-28 weeks of gestation. Those with other factors such as preeclampsia, kidney or liver disease and those taking other probiotic products such as yogurt or kefir were excluded from the study.   -24 in the probiotic group and 24 in the placebo group	-Primary outcome was the expression of PPAR-Y gene (which enhances glucose metabolism)  -other metabolic and genetic profiles were considered secondary outcomes.	-they found that probiotics upregulated the expression of PPAR-y gene (which enhances glucose metabolism)   -decreased fasting plasma glucose and insulin resistance and increased insulin sensitivity.   -probiotics also decreased triglycerides and increased HDL cholesterol.   -Had overall beneficial effects on inflammation, glycemic control, and oxidative stress.	-one limitation was the sample size of 48 people, which was small.  -another limitation was that they did not measure the fecal bacteria load in the patients before and after the probiotic supplementation to see the effects.   -Overall, there was minimum bias due to the design of the study.
6. Do probiotics effectively ameliorate glycemic control during gestational diabetes? A systematic review    Dallanora, S., Medeiros de Souza, Y., Deon, R.G. et al  2018	Systematic Review	-out of the 31 articles that were identified, 7 of them met the inclusion criteria of being an RCT.  -these articles had a sample size of 60-373 women with GDM that was identified between 24-40 weeks of pregnancy.	-the primary outcome was the effect of probiotics on glycemic control  -the secondary outcome was the effect probiotics had on other metabolic factors.	-found that probiotics used during the pregnancy in women with GDM were able to improve their overall glycemic control and reduce metabolic factors such as VDL, triglycerides and other inflammatory markers	-one major limitation of this study is that there is not a lot of published work on these topic. Hence some information may be lacking in this review, due to the fact that they did not include any unpublished data or reviews in their meta-analysis

  

Conclusion(s): 

Briefly summarize the conclusions of each article, then provide an overarching conclusion.  

Article 1: This article was a systematic review that focused on one RCT in particular that included 256 women. They found that if probiotics are given early in pregnancy, it greatly reduce the risk of gestational diabetes. However they found that there was not enough evidence to speak on the effects of probiotics and the rates of neonatal stress including miscarriages, still birth, death, ICU admissions, and macrosomia. More research is needed to formulate a thorough metanalysis on this topic.  

Article 2: This article was a double-blind RCT that was done on 149 women. They looked at the effects of probiotic supplementation on both glycemic control as well as its metabolic effects. They found that probiotics had not significant impact on the glycemic control of patients with GDM. However they found that probiotics had a significant impact on the reduction of the pregnancy induced rise in total and LDL cholesterol. However, this is not enough to make a solid judgement on the effects of probiotics for women with GDM, and further randomized trails are needed to assess its validity.  

Article 3: This article was a double blind RCT with a total of 507 participants. This study focused on the effect of probiotics on pregnant women that were in their first half of their second trimester (14 weeks) up until 24 weeks. They found that probiotics at this time does not reduce the risk of GDM or show improvements in neonatal outcomes. However this article addresses the need for further studies using different species of probiotics, at different doses and given in different intervals.  

Article 4: This article was a double blind RCT that was done n a total of 411 pregnant women. This study mainly focused on women that were obese or overweight. They found that probiotics given throughout the second trimester of pregnancy does not reduce the frequency of GDM at 28 weeks gestation. They also found that probiotics did not seem to improve secondary outcomes as well. However, they did find that there was a significant reduction in SGA (small for gestational age) in the babies that were born to the women that were taking the probiotics.  

 Article 5: This article was a double bling RCT that was done on a total of 48 patients using the probiotic capsule containing “Lactobacillus acidophilus, Lactobacillus case, Bifidobacterium bifidum, Lactobacillus fermentum.” In this study they gave the experiential group probiotics for 6 weeks and assessed their effects. They found that the patients taking the probiotics had beneficial effects on gene expression (PPAR-Y), that is related to inflammation, insulin and glycemic control. They also found that probiotics had a beneficial effect on lipid profiles and oxidative stress.  

Article 6: This article was a systematic review of 7 articles that had sample sizes from 60-373 pregnant women with GDM. This study found that probiotics were helpful in improving glycemic control and reducing inflammatory markers in women with GDM. They also found probiotics helped reduce VDL cholesterol, triglycerides, and total cholesterol. Further studies are needed on this topic.  

 

Clinical Bottom Line: 

Weight of the evidence: summarize the weaknesses/strengths of the articles 

Article 1: This study of 256 women shows a 60% decrease in the rate of diagnosis of gestational diabetes mellitus in women taking probiotics from early pregnancy Strengths of this article include that it is a systematic review, that focused an RCT that had a total of 256 patients. However, this is also a weakness, in that for it to be a strong systematic review, it should have included more then just one article. Also another weakness is that it only looked at the effects of probiotics in the reduction of cases of GDM, and did not assess other outcomes such as macrosomia, risk of miscarriage or still birth.  

Article 2: This article showed that the probiotic did not appear to have any beneficial glycemic effect or benefits to pregnancy outcomes, it dud however have subtle positive effects on cholesterol levels. Strengths of this article include the fact that it was a double blind RCT, this allows there to be limited bias since both the patient and experimenter are blind to whether they are receiving the probiotic or placebo. Another strength is that they looked at outcomes other then GDM, that can also have a significant effect on mother’s health, including metabolic factors. Even though they didn’t see a clinical significance in probiotics helping GDM, they did see that probiotics lead to a decrease of total and LDL cholesterol. Weakness include a sample size of only 149 patients, and a high dropout rate of 18%. 

Article 3: This study shows that the incidence of GDM in the intervention group/ probiotic was 41.9%, and the incidence in the control group was 40.2%, which is not significantly different. Strengths of this article include the fact that it is a double blind RCT, allowing for reduction in bias and increased focus on the treatment in question. Also this study have a very large sample size, this allows for a more accurate depiction of the results. This also assessed both risk of GDM as well as other maternal and neonatal factors such as abnormal growth, ICU admission and need for C-section. However, one weakness is that they only looked at how probiotics would effect the patient if they were given for a short period of time (14-24) weeks, which is not enough time to comment on the effectiveness of the treatment.   

Article 4: The results of this study showed that out of a total of 411 patiens, which were then spilt into 204 in the placebo group and 207 in the probiotic group,  GDM occurred in 12.3% of the patients in the placebo arm and 18.4% of the patients in the probiotics arm. This shows that the probiotics used in this study did not prevent GDM in overweight pregnant females.  Strengths of this article include that it was a double blind RCT for the similar reasons as mentioned above. Also this study had a large sample size of 411 patients, giving a more accurate picture of their findings. A weakness was that they only looked at the effects of probiotics for a short period of time, from the second trimester up until the 24th week mark. Also, some women were recruited after 20 weeks of gestation, giving them a 4 week treatment window which does not allow sufficient time to see a response.  

Article 5: This study showed that overall probiotic supplementation for 6 weeks to patients with GDM had beneficial effects on their gene expression related to insulin and inflammation, improved glycemic control, few lipid profiles, and oxidative stress. Strengths of this study included that it’s a double blind RCT allowing for the focus on the treatment as well as limiting bias. Also this article focused the genetic and metabolic profiles of probiotics and GDM, such as how probiotics effected the expression of PPAR-Y gene, which influences glycemic metabolism. They also focused on how probiotics effects other metabolic factors such as cholesterol, inflammatory markers, and oxidative stress. A major weakness of this study was the small sample size of only 48 patients, as this does not allow for accurate measure of the results.  

Article 6: The 7 articles looked at in this systemic review highlight the importance of probiotics for glycemic control  and prevention of GDM and decrease of inflammatory markers in those females who already have GDM. strengths of this study include that it’s a systematic review, that looked at 7 articles. This allows for a better more complete picture of the treatment process. Also the studies had sample sizes ranging from 60-373 women, which allows for a large sample size to see accurate results. A weakness is that there still needs to be more studies done on this topic in order to formulate a better meta-analysis.  

Overall:  

Over all, there was a split amongst these articles about the beneficial effects of probiotics on glycemic control and the reduction of GDM in pregnant women. Some of the studies found that the probiotics did in fact reduce the risk of developing new onset GDM or even improving the glycemic control in those women that already had GDM. However some of the studies showed that there was no impact of probiotics. However, it is to be noted that a majority of these studies found that probiotics did influence metabolic factors that could lead to secondary adverse effects such as HTN, complicated birth, etc. They found the probiotics were able to reduce the total and LDL cholesterol as well as reduce inflammatory markers and oxidative stress. Since probiotics help improve overall gut microbiota, I think that it is something beneficial that pregnant women can add to their prenatal care, as it can only hep them and not adversely effect them. I also think that if added with a healthy diet and exercise regimen, this can show a significant impact. 

 

Magnitude of any effects 

I believe that the magnitude of effect was significant enough to allow for the discussion of the use of probiotics for the prevention and management of gestational diabetes. Articles 1, 5, and 6 showed that probiotics had a direct impact on the reduction and improvement of gestational diabetes. 2 of these articles were systematic reviews, and one was a double blind RCT that had a small sample size, this doesn’t allow for a complete picture of the benefits of the treatment. Articles 2, 3, and 4 had a much larger sample size and concluded that even though probiotics did not have a significant effect on GDM, they did help with other maternal metabolic factors such as improving glycemic control, reducing VDL, LDL and total cholesterol, controlling inflammatory markers, and also reducing the risk of infants being born with SGA. This is important because even though, it did not a direct cause and effect, the probiotics do effect other helpful aspects of maternal wellbeing, and thus should be something that can be added as a regular supplementation while pregnant. It is also important to note that they will have the best outcome, when they are started early in gestation. However, more studies are needed on various species of probiotics, along with various doses and intervals.  

 

 Clinical significance  

I believe that this PICO topic has great clinical significance, because of the increased rates of pregnant women in the US getting diagnosed with gestational diabetes everyday. This not only effects the pregnancy adversely, but can also have adverse effects on the mother and infant in the long run, and needs to be addressed early on in order to reduce the risk of getting it or improve the glycemic control in those that already have it. I also think that especially in pregnancy, a lot of women are very cautious of the medications they takes anything can adversely effect the growing fetus. After trying diet and exercise, another safe place to turn to is supplements and probiotics, as they have great benefits with little to no side effects. In our day to day lives we are encouraged to take probiotics to improve out gut health and microbiota, so it is logical to think that it can have an impact on improving metabolic factors and glycemic control in order to better manage the risk of gestational diabetes.  

 

Any other considerations 

I thought this PICO question was very interesting, because in the past few years the use of vitamins, supplements probiotics has increased significantly as a lot of people are trying to heal and prevent ailments more organically rather then traditional medication. However, certain other considerations include that a lot of the studies looked at one specific type of probiotic (with a mixture of Lactobacillus acidophilus, Bifidobacterium longum, and Bifidobacterium bifidum), rather then testing out several other types to see how they would effect the rate of GDM. Also a lot of the studies also looked at only given the probiotic at a particular time in gestation (such as early on, or during the second trimester). Supplements can have different effects if they are given at different times and in different intervals, and I believe the future studies need to be done that address those issues, in order to create a more thorough conclusion.