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

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.

Non-invasive fetal RHD genotyping for RhD negative women stratified into RHD gene deletion or variant groups: comparative accuracy using two blood collection tube types.

Non-invasive fetal RHD genotyping in Australia to reduce anti-D usage will need to accommodate both prolonged sample transport times and a diverse population demographic harbouring a range of RHD blood group gene variants. We compared RHD genotyping accuracy using two blood sample collection tube types for RhD negative women stratified into deleted RHD gene haplotype and RHD gene variant cohorts. Maternal blood samples were collected into EDTA and cell-free (cf)DNA stabilising (BCT) tubes from two sites, one interstate. Automated DNA extraction and polymerase chain reaction (PCR) were used to amplify RHD exons 5 and 10 and CCR5. Automated analysis flagged maternal RHD variants, which were classified by genotyping. Time between sample collection and processing ranged from 2.9 to 187.5 hours. cfDNA levels increased with time for EDTA (range 0.03-138 ng/µL) but not BCT samples (0.01-3.24 ng/µL). For the 'deleted' cohort (n=647) all fetal RHD genotyping outcomes were concordant, excepting for one unexplained false negative EDTA sample. Matched against cord RhD serology, negative predictive values using BCT and EDTA tubes were 100% and 99.6%, respectively. Positive predictive values were 99.7% for both types. Overall 37.2% of subjects carried an RhD negative baby. The 'variant' cohort (n=15) included one novel RHD and eight hybrid or African pseudogene variants. Review for fetal RHD specific signals, based on one exon, showed three EDTA samples discordant to BCT, attributed to high maternal cfDNA levels arising from prolonged transport times. For the deleted haplotype cohort, fetal RHD genotyping accuracy was comparable for samples collected in EDTA and BCT tubes despite higher cfDNA levels in the EDTA tubes. Capacity to predict fetal RHD genotype for maternal carriers of hybrid or pseudogene RHD variants requires stringent control of cfDNA levels. We conclude that fetal RHD genotyping is feasible in the Australian environment to avoid unnecessary anti-D immunoglobulin prophylaxis.

How have the lives of pregnant women changed in the last 30 years?

BACKGROUND: To what extent have the characteristics and needs of pregnant women changed over time? This cross-sectional, comparative study describes some socio-demographic, mental health and lifestyle characteristics of two samples of pregnant women assessed 30 years apart. METHODS: We recruited two samples of pregnant women who were attending their first clinic visit at the same large Queensland maternity hospital 30 years apart between 1981 to 1984 (Sample A, N=6753) and 2011-2012 (Sample B, N=2156). The women were compared using the same survey tool. Descriptive statistics are presented. Pearson's chi-square tests were undertaken (significance at <0.05) to determine how the characteristics and needs of pregnant women may be changing over time. FINDINGS: Women, recently sampled, were older, more highly-educated and were more likely to be living with, but not married to, their partners, as well as having their first baby, than were women 30 years ago. As well, recently sampled, pregnant women were more likely to be non-smokers, to have higher body mass indexes and more symptoms of anxiety, but were less likely to be having an unplanned pregnancy. CONCLUSION: This study found a number of differences between the socio-demographic characteristics, lifestyles and mental health of two samples of pregnant women assessed 30 years apart. Our findings suggest the need for ongoing monitoring of pregnant women to determine changing health priorities. Being more educated, today's women may be more amenable to health education interventions. Higher body mass indexes for recently sampled women, highlights an emerging problem that needs to be addressed.

Strategy for managing maternal variant RHD alleles in Rhesus D negative obstetric populations during fetal RHD genotyping.

OBJECTIVES: Fetal RHD screening programs that aim to reduce unnecessary antenatal anti-D prophylaxis are being introduced into clinical practice. Strategies to manage women serologically typed as Rhesus D negative who have maternal RHD variants are needed. This study describes maternal RHD allelic variants detected in nonselected and alloimmunised Rhesus D negative obstetric populations and explores a mathematical approach to identify these variants. METHODS: Fetal RHD status was defined by testing cell-free fetal DNA in maternal plasma. Women at risk of an RHD variant were identified by selection for C and E haplotypes or by recognition of low polymerase chain reaction cycle threshold on fetal RHD typing. Maternal RHD alleles were defined by SNP profiling or sequencing. RESULTS: The prevalence of RHD variants in nonselected and alloimmunised groups was 1% (6/603) and 5.5% (6/110), respectively (p < 0.001). An inverse association between RHD cycle threshold values and gestational age was described by a linear model (p < 0.001). Standard residual values with a Z score threshold of -3.00 would have detected all maternal variants with one (1/713) false positive. CONCLUSIONS: The prevalence of maternal RHD variants was significantly higher in alloimmunised cases. The causative mechanism for this needs further investigation. Mathematical modeling simplifies the detection of maternal RHD variants.

SPRING: an RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women.

BACKGROUND: Obesity is increasing in the child-bearing population as are the rates of gestational diabetes. Gestational diabetes is associated with higher rates of Cesarean Section for the mother and increased risks of macrosomia, higher body fat mass, respiratory distress and hypoglycemia for the infant. Prevention of gestational diabetes through life style intervention has proven to be difficult. A Finnish study showed that ingestion of specific probiotics altered the composition of the gut microbiome and thereby metabolism from early gestation and decreased rates of gestational diabetes in normal weight women. In SPRING (the Study of Probiotics IN the prevention of Gestational diabetes), the effectiveness of probiotics ingestion for the prevention of gestational diabetes will be assessed in overweight and obese women. METHODS/DESIGN: SPRING is a multi-center, prospective, double-blind randomized controlled trial run at two tertiary maternity hospitals in Brisbane, Australia. Five hundred and forty (540) women with a BMI > 25.0 kg/m(2) will be recruited over 2 years and receive either probiotics or placebo capsules from 16 weeks gestation until delivery. The probiotics capsules contain > 1x10(9) cfu each of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB-12 per capsule. The primary outcome is diagnosis of gestational diabetes at 28 weeks gestation. Secondary outcomes include rates of other pregnancy complications, gestational weight gain, mode of delivery, change in gut microbiome, preterm birth, macrosomia, and infant body composition. The trial has 80% power at a 5% 2-sided significance level to detect a >50% change in the rates of gestational diabetes in this high-risk group of pregnant women. DISCUSSION: SPRING will show if probiotics can be used as an easily implementable method of preventing gestational diabetes in the high-risk group of overweight and obese pregnant women.