 So, first of all I'd like to welcome everyone to this virtual international day of the mid-wifes at such a fantastic session and, you know, really a special thing that we do in New Zealand and around the world so we're really quite excited about it. I'd like to thank the sponsors, the University College at Lilibet and also the Association of Radical Midwives for supporting this amazing conference. How should I move the slide? And of course that college is in Denmark and of course the Association of Radical Midwives is around the world. So just in case you're wanting to do some setting up as well, you can go to the meeting and work your way through the audio setup wizard. It's up on the black ribbon at the top, under meeting, in the dropdown from meeting and that will enable you to work through and test out your sound and test out your ability to speak if that's something you may like to do later in the session. And the chat window down here which most of you seem to have found and people are chatting away in it now. You can make comments in the chat box. But please keep the comments relevant so that they're not going to distract the speaker. So keep them on message. If you need to talk to other participants, you can use the private chat and that's by hooking on that little, what is it, a waffle or something at the top there on the right hand side. So to give us feedback, you can go to the top of your screen and you'll see there's the icon of the person with their hand up and that's if you're wanting to ask a question. Also if you agree with what the speaker is saying, you can click agree or disagree. If you need to step away, you can click the one on step away and so on. Or you can prompt them to speak louder or speak softer. And I'll be keeping an eye on those for Robin. Robin has suggested that unless she takes a break in some part of her presentation, that she would like us to keep the question for the end so that she's not too distracted and she doesn't run out of time. So we'll do that today. If you want to ask a question or make a comment, you can use the chat window. Connect your microphone. Once the host has given you the microphone, you will see a symbol of a mic next to your name in the attendee's box. So to speak, you just click on that mic symbol at the top next to speaker symbol and allow to flash player. You know you can speak because the mic will turn from white to green. If people tell you they cannot hear in the chat box, click on the microphone symbol and that will adjust your microphone volume. When you've finished speaking, disconnect your microphone otherwise we're likely to get feedback. Right. That's for me. Turning on the recording. I don't have the option to turn it on. It's up here. Is it already meeting with being recorded? Okay. Yeah, it's already meeting with being recorded. Ah, thanks. That threw me. Right. So now it gives me great pleasure to welcome Robin Mord. Robin is a senior lecturer at the Graduate School of Nursing Midwifery and Health at Victoria University of Wellington in New Zealand. And Robin continues to provide lead maternity care for a small case load of women birthing in hospital and at home. Robin's research interests are largely clinically focused on activities that promote and protect the normal physiological births. These include fetal heart monitoring and fetal movement, water immersion and water birth, medical legal aspects of the provision of care, knowledge translation, knowledge to action process, quality improvement and clinical effectiveness, continuity of midwifery care, standards of midwifery practice, models of midwifery, midwifery leadership and the use, and now the use of probiotics and pregnancy. So that's quite a list, Robin. So welcome and we're really looking forward to hearing from you. Thank you. Hi, Jean and hi everybody. I hope you can hear me but if you are having trouble just make sure you put a message there so I can bring myself closer to the microphone. Jean can everyone hear me or can you hear me now? I can hear you, Robin. Lovely. We did have a bit of trouble at the beginning getting it sorted out so I hope that you can hear me and I'll talk nice and loud. So thank you for allowing me to present this piece of research today which is about the use of probiotics and pregnancy. I'm just going to take you through a fairly sort of formal slide set up around how to report on a piece of research that's been done and I hope that you'll enjoy it and I hope at the end that you'll be able to ask me some questions about it but not too many tricky questions. Welcome to everyone and happy international day of the midwife. We've had a lovely day here in Wellington, New Zealand. It's sunny and we had a lovely picnic and rally down on the steps of our parliament which was well attended by mothers and babies in midwives so happy midwives day everybody. So to begin with I'll talk about the probiotic and pregnancy trial. So the World Health Organization has defined probiotics as live micro-organisms which when administered in adequate amounts confer health benefits to the host. And there's emerging evidence for a modulating effect of probiotics on gut microbiota and inflammatory responses. With a recent meta-analysis suggesting that probiotics can favorably influence glucose metabolism. And that's what I'm going to be focusing on today in terms of this presentation. So some of the background to this is that we know lifestyle factors such as changes in the patterns of food consumption with economic development have led to the well-recognized and increasing problems of obesity and associated diseases including gestational diabetes mellitus both here in New Zealand and around the world. Pre-pregnancy overweight and obesity have been shown to account for about 46% of GDM with excess weight gain during the pregnancy. Previous GDM or a family history of diabetes, polycystic ovary syndrome, older age and high parity are also identified as risk factors. GDM itself increases the risk of preeclampsia, miscarriage, preterm, labour, macrosomia, induction of labour and caesarean section. GDM also increases the risk for later maternal and child obesity and subsequent type 2 diabetes. A previous Finnish study showed that probiotic supplementation containing lactobacillus ramnosus GG and Bifidobacterium Lactis BB12 taken from the first trimester of pregnancy reduced the prevalence of GDM. So this study that we have just recently completed aimed to investigate whether the probiotic lactobacillus ramnosus HN001 taken by women during pregnancy would reduce the prevalence of GDM by the 26-28 weeks gestation. The main trial was geared to investigate the rates of infant eczema and atopic sensitisation by one year. But we included secondary outcome measures which included maternal gestational diabetes, bacterial vaginosis, group B streptococcal, and depression and anxiety postpartum. So this trial was a double, a two-cented double-blinded randomised placebo-controlled parallel trial. My God, that's a mouthful. There were two study groups of 423 pregnant women and the intervention was the lactobacillus ramnosus HN001 and the placebo which was a maltodextrin mixture. One capsule was delivered to the women at 14-16 weeks gestation and continued on right until six months postpartum if breastfeeding. We did not include any alteration to the maternal diet in this particular trial. The participants were pregnant women from Wellington and Auckland in New Zealand and as I said earlier they were enrolled very early in their pregnancies from 14-16 weeks and this certainly created quite a challenge for us to be able to access those women or to get the information to those women early enough in their pregnancies. So we did engage the use of scanning people that provide early pregnancy scans, GPs, midwives, and a range of other people to help us to recruit. There were 423 women randomized, as I said, 212 in the provided group and 211 in the placebo group. The eligibility criteria for women, keeping in mind that this trial was about reducing eczema and asthma and atopy, was that the mother or the infant's biological father had a history of diagnosed asthma, eczema, or hada fever treated by a doctor, that the woman intended to breastfeed, that there were no serious immunological disorders or immune suppressant medication or heart valve disease, that the woman did not require IVF to establish pregnancy and did not intend to use other probiotics nor continuous antibiotic or steroid medication. We excluded anyone who had had a transplant or HIV infection and so that was the group. The power calculation was done on an assumption of a 15% prevalence of GDM, a 63% reduction due to probiotic as was found in the Finnish study, which gave a sample size of 195 in each group. The baseline information that we collected from the women were these things here on the screen. Amongst women with previous pregnancy is greater than 20 weeks. We also collected a history of previous GDM and the birth weights of their previous babies. In terms of the assessment for GDM, we used the international guidelines, which are there in the first column of that, second column of that chart you can see now. But we also used the New Zealand cut-offs, which you can see are slightly different. And those cut-offs come from the Ministry of Health in New Zealand and the international ones are the International Association of Diabetes and Pregnancy Study Group's consensus panel. So the assessment for GDM was conducted at 24 to 30 weeks gestation following a 12-hour overnight fast using a glucose tolerance test undertaken at the community laboratories. Only women without pre-pregnancy diabetes were invited to undertake the study GTT. Women who received a GTT-based diagnosis of GDM prior to the study GTT were included in the study outcomes only if there was evidence of earlier negative results, negative tests confirming that diabetes was gestational. When repeated GTTs were performed later in pregnancy for clinical purposes, the tests completed at 24 to 30 weeks gestation determined their status around GDM. So women with GDM were asked to have a postpartum HbA1c at three months after birth. A postpartum HbA1c level of greater than or equal to 6.5% or 45 millimoles per microliter, or a postpartum fasting glucose of greater than 7%, was used to indicate the presence of coexisting type 2 diabetes. If women meet these criteria, they are excluded from the GTM analysis. We collected other outcomes at four to seven days postbirth, including maternal weight, waist circumference, gestation in weeks of the birth, prematurity, infant at gas scores at five minutes and birth weight, infant length, ponderal index, head circumference type of birth and admission to the neonatal intensive care unit. Analysis was performed using intention to treat relative rates were used to assess effects of the study group on gestational diabetes and birth outcomes. Continuous variables, differences between the study groups were compared with the Wilcoxon rank sum tests and T tests, and a p-value of less than 0.05 was considered statistically significant. So, some of the results that we have found so far. And for all of these factors, we saw that there was no substantial difference between the study group in any of these characteristics and enrollment. So, the groups were very, very similar in terms of age, ethnicity, parity, weight, et cetera, which is always a good place to start. The GTM assessments were completed by February 2015, and the final infant was born in May 2015. Here is the first result. And this one looks at the HN001 effects of GDM prevalence using the international and the New Zealand cut-offs. Oops. Oh, here we go. There it is. I was looking for my circle, and I found that a total of 194 or 92% of the women in the HN001 group and 295% in the placebo group participated in the GTT assessments, all of whom were able to contribute data to the analysis on the basis of the New Zealand guideline. Result one shows that the prevalence of GDM using the international criteria in the HN001 group were lower than in the placebo group. But this difference was not statistically significant. As you can see, the P value at the bottom there being 0.08. However, if you use the New Zealand cut-offs, there was a significant finding, and the prevalence of GDM was slightly lower in the probiotic group. The probiotic group showed a reduction in GDM prevalence. Using the New Zealand guidelines, that reduction was 68%. Using the international guidelines, the prevalence was reduced by 40%. Now looking at the second result, and there are three aspects to the second result, and the first one is the effect of the probiotic stratified by maternal age. Using the international guidelines, the protective effect of the probiotic was significant in women aged 35 and over. In the older group, the probiotic was associated with a threefold reduction in the prevalence of GDM compared to the prevalence among women in the placebo group. In women aged less than 35, I haven't got one for that, sorry I'll go back there, in the women aged less than 35, the prevalence in each of the study groups was similar. There were no significant differences in effect dependent on whether BMI was greater than 30 or less than 30. The second finding in this part relates to the effects of the probiotic stratified by history of GDM. GDM did not occur in any of the probiotic participants who had a previous history of GDM, and that's quite an important finding. Among those with a history of GDM, the probiotic protected against the recurrence of GDM, and for those without previous diabetes. And here's the next result in this section, and this is the effects of the probiotic stratified by antibiotic use. And as we know, certainly in New Zealand, and I'm sure that it's the case around the world, the use of antibiotics in pregnancy and labour now seems to be soaring, and we really do have to take care and think about the effects of this. So as the probiotic is susceptible to a range of antibiotics, we examine the effect of the probiotic on GDM by use of antibiotic between study enrolment and the GTT. The probiotic effect on GDM was significantly protective among participants who had not used antibiotics between study enrolment and the GTT test, but there was no significant effect of the probiotic for those women who had used antibiotics during the same period, which you can see in the result on the left-hand side of the screen. So that's an important finding. Similarly, amongst those not using antibiotics, fasting mean blood glucose levels were significantly lower in the probiotic group compared to that in the placebo group. Looking at the results in this part now, there was no significant difference in the measurements, in the effect on infant or maternal anthropometric, well that's hard to say, measurements. And those are the things such as BMI waste measurements during section gestational age, infant birth weight, infant length, ponderol index or NICU admission. So no significant differences there. However, there was a significant difference in the 5-minute APGAS scores, which were significantly higher in the probiotic group. And you can see the results there. So 98.5% of babies in the probiotic group had a 5-minute APGAS score of greater than or equal to 7, and that was a P score of 0.04. So there was a lot of discussion to be had around this, and it was interesting for us to have these particular findings. We come up with a conclusion that says probiotic HN001 supplementation in pregnancy may reduce the prevalence of GDM amongst, particularly amongst women aged 35 and over, and for those who have had prior GDM. There's no doubt that at this stage we don't actually have any thoughts around why the APGAS score should be different. However, in the paper that we've written around this, it says that it could well be due to the chance given to the number of comparisons performed. So it may be something that has to be looked at in future research that happens around the use of probiotic. So the lack of any deleterious effect on the birth outcome supports that the probiotic has a safe intervention to take from early pregnancy, which may also be beneficial to the baby, as reflected in the APGAS score. And these findings are important, given the small amount of data available on the effects of early pregnancy probiotic intervention. So we thank the women and also the medwives who generously gave their time to the study. I'd like to show you that this paper has been published in the British Journal of Nutrition this year. It's available on open access. And the key author there, the lead author, is Kristen Wickens. And the study group are all stated there. So you can download this article, this publication for free and read the full paper looking at the different findings. Also coming is a publication that has shown the effects of the same lactobacillus ramnosis HN001 used in this trial on postpartum symptoms of depression and anxiety. So look for that paper that will be coming out soon this year. And also a paper that will be written that has been submitted to talk about the effects on eczema and atopy. So those ones will be coming out. That will be in the Journal of Allergy and Clinical Immunology that's been submitted this year as before as well. So there was a last slide that shall I use it? Okay, so the previous study, this group of people have been developing a sort of platform of study around the use of this particular lactobacillus. And the previous study, which was done back in 2009-2010, shows that when this probiotic was taken by pregnant women from 35 weeks gestation to six months postpartum of breastfeeding and given daily to the baby from birth to the age of two had a significant reduction in the prevalence of eczema at the age of two, four and six. So they concluded that a protective effect against atopic sensitisation did not become significant until six years of age. But the protective effect against eczema and asthma was quite strong. So there's a whole body of research that is building around the use of this particular lactobacillus. However, you know that there are lots of other lactobacillus around. So that's where I finish and I'm very happy to take questions. The long is the easy one. Thank you, Robin. That was great. A very interesting study to be involved in. I haven't seen any questions come up yet, so I hope you get busy with your questions because Robin's got plenty of time to respond to them. I've just got one. I'm really interested in the A-typey one. That's interesting that it didn't have any protective, well, not significant protection given during pregnancy, but it seems to be something where you're signalling that given to, is it to the baby? Breastfeeding. Yeah, and so that direct injection of microbiome to the baby. That's interesting. And I'm just wondering what sort of, well, how do they test your biome if they want to know if this was an appropriate mix of lactobacillus to offer you? Is there some way? Because some people have got better ones than others. Yeah, well, it's interesting because part of the samples that we took from mother and baby included breast milk samples from about day three to day five. We took fecal samples from both the mother and the baby. And those are undergoing testing even now so that we can look at not only the mechanism of what happens, but also there's some really interesting epigenetic studies that can be done, but that requires more funding at this stage. We also took cord blood and cord tissue samples, and those are currently sitting in minus 80 degrees waiting for more funding. And they will particularly be looking at the epigenetic effects, but the mechanisms are determined through things like fecal samples and the breast milk samples, which are really interesting. And a lot of that is outside of what my understanding is, but still incredibly interesting to think what can be achieved by looking at those particular samples. While I've got your attention, Robin, in terms of coming back to this, there's been a lot of material in the nutrition journals and filtering down to listeners and things like that about the different foods that people eat and how that affects their biome. And I wonder if there was any kind of record of the participants' diet apart of this study as well? Yes, it was. Thanks, Jean. The women were asked to keep food diaries, and so those food diaries went for a period of time and they were part of the analysis. And there's many more papers that will come out of this, but certainly analysing their food intake was definitely part of the data that was collected. I think that's really interesting. I think that's resolved most of my questions. I haven't seen any others come up. Has someone got a question for Robin? There must be heaps of them sitting out there. Aval's typing. So it looks like you've got a job for life, Robin. I think that, you know, on a sort of a sidebar, really, for a midwife, a midwife researcher, to be able to get involved with a team of people who have a strong platform of study is a really interesting thing. And this probiotic RCT was probably outside what I was ever thinking that I might be able to get involved with. But I became involved as a midwifery advisor so that I could link the team with midwives and really to moderate how they develop their protocol, particularly thinking about how midwifery and how women and midwives work in partnership here. So a really excellent opportunity for me to learn such a lot by becoming part of a study team. And the team are called the Wellington Asthma Research Group. So that's really where the focus of their attention is. But as we are starting to see more and more research around the use of probiotic, and as we're starting to understand more and more about the gut microbiota and how that affects, you know, our immune systems and our brain and just about everything else you can think of, it's probably a really important area for us to be involved with. And I know, you know, from my practice as a midwife... Sorry, Jean. No, I was just going to say how, you know, why do you've got all those really close-to-practice interests that we talked about in your bio? I mean, your bio. My bio? What your bio? I mean, it really does fit, doesn't it? Because this is something that might make a huge difference that is low-key and a natural product that would make such a big difference. And it was really interesting in the early stages of trying to recruit when we knew that, you know, there are increasing numbers of women who are hearing the story about probiotic, and so they are already taking probiotic. And of course some of the women, because these women recruited on the history of asthma, eczema and atopy, they were saying, just tell me what the name of the probiotic is so I can get on with it. So that made it quite difficult for us to recruit. Averill... Yeah, Averill's got a question right on target there, and I'm just going to say to you, Averill, there's no such thing as a silly question. And good on you for being a first-year student, so we'd love to hear from you. The particular probiotic that was tested in this trial is called lactobacillus ramnosus HN001. And it's produced by Fonterra. If you were to look at the label of probiotics that are available in shops, you would see very clearly the names of some of the probiotics that are used. There is one probiotic on the market in New Zealand that does contain this particular strain of lactobacillus. Of course, the other strain that was tested by the Finnish team was the lactobacillus ramnosus GG. So in New Zealand, you can purchase this particular probiotic. Hope that helps. Sorry, Ginger, I'm interested to know that two... as not being in New Zealand, what is available? Yeah. I'm not sure where you live, Ginger, but again, it would be about carefully looking at the label and seeing what they say. Are probiotics available in Uganda? Okay, fair enough. We'll be looking for these particular strains then. Bacillus ramnosus HN001 is the one that was used in this study. As I say, there's such a lot of emerging data now about the use of probiotic, not just for this, but this is exciting because this specifically has an impact on the prevalence of GDM. And I think coming back to what this presentation is about, it's actually about how do we reduce some of those conditions that are really impacting on how we attempt to keep this normal for women who have issues with diabetes and obesity. So if we can also help women understand their nutrition and modify their diets and maybe reduce their use of antibiotic and maybe increase their use of probiotic, then I believe we can probably help to stem some of the prevalence of obesity and high BMI. So for women over 35 who have not even had GDM in the past, this is effective in terms of preventing GDM. There's a question there from Tammy from New Zealand Home Birth Midwife. Most of my clients actively take probiotics with many using their own probiotics in home produced foods such as saucrot, which also helps with morning sickness. So this is what you were talking about, really, Robyn, isn't it about some adjustments to diet and so on? Yeah, and we're aware of that, Tammy, that certainly there are a lot of women and midwives who actively have those discussions about home produced foods that do contain things like probiotic. And certainly probably one of the next trials we will look at is a combination of prebiotic and probiotic. And prebiotic is those found in the home produced foods such as saucrot and oats and those sorts of things that are used to modify diet. So the next trial probably will contain both prebiotic and probiotic to see if that has an effect as well. I didn't ask, Robyn. Yeah, go on. There you go. A question I didn't ask about the study was what was the rationale for choosing those two intervals to give it and that particular dosage? Was there anything that supported that? The interval, getting it early was to, because it was used earlier in the Finnish study, they did that in the first trimester. The previous study conducted by this group was administering that 35 weeks through to six months. So there was a hypothesis generated that if you gave it earlier to women during pregnancy that it may have a bigger effect on the reduction of asthma and eczema and atopy by passing through the placenta during those times. So this trial was deliberately to try seeing if it would have a greater effect being administered earlier and it also gave us an opportunity to include those maternal outcomes as well. Excellent. Are there any further questions? I'm just conscious we've got two or three minutes left. Is there any burning questions for Robyn? Avril's typing. I was wondering about those there, Avril. I've got that written down. I've got that written down. Let me just find it for you. Lactobacillus Ramnosus 18001, and this is really complicated, Avril. It's 9.15 by 10 to the power of 9 coliform forming units per capsule. So that's managed by the producers and they do the testing around that to make sure that there is that degree of live coliform forming units available in each of the capsules. So because they are live obviously and it needs to be checked. So very high rates. Yeah, and I think Avril you're saying so that is just standard and they do it. In terms of the trial, they produce the bacteria and they manage to keep it live and to keep it consistent across all of the capsules and they check it on a regular basis. They check any capsules that get returned at the end of the trial that haven't been used to see that they've maintained that same level of potency. So yeah, I see Ginger is going, and I know that that's very complex, but the degree of potency is significant and you have to have some consistency around that and that's managed by the people in the trial. Well, it's been really, really interesting Robin. Is there any final, just one minute to go if you've got a burning question and then we need to thank Robin and get ready for the next speaker. Thank you for listening to me everybody. I hope that it was interesting to you and I hope that you will access those journal articles and have a read so it makes a little bit more sense. But the take home message is this particular probiotic has an effect that is positive for reducing gestational diabetes in women who are over 35 and that's a good thing, that's a good thing to know. So thank you for listening. Thank you very much and I'm sorry Robin it was such a hassle for you at the very outset that we'll finish the recording now. Do I just pause?