In this episode of WiGH, Lucia Arico-Muendel speaks with Dr. Valerie Flaherman about her research on how breastfeeding and formula-feeding regimens affect infant growth during the first month of life, mainly in low-income countries such as Guinea Bissau and Uganda.
Dr. Flaherman is a pediatrician and global health researcher at the University of California, San Francisco. Her research focuses on breastfeeding, breastmilk, lactation, and infant nutrition, overall aiming to improve health outcomes in at-risk infants through targeted interventions. She travels to Uganda, Guinea Bissau, Pakistan, and Nepal to set up studies with partner institutions.
Transcript (via Sonix)
Lucia Arico-Muendel: [00:00:02] So I’m here with Valerie Flaherman, who’s an M.D., M.P.H., at UCSF, and we’re just going to be talking a bit about her research and some COVID complications. As with everything else, these last few years have been more difficult due to COVID. So just to get started, I would love to hear about your research. Everyone at Columbia who listens to this podcast is interested in public health and public health research techniques. So how did you settle on your your focus, what inspired your project and Uganda and Guinea-Bissau? How long have you been doing this work?
Dr. Valerie Flaherman: [00:00:55] Well, thank you so much for having me here today. It’s good to be here and to talk about this. And one of the topics I’m really passionate about is newborn feeding and growth, because I think there are so many barriers to infants in low and middle income countries, even if they’re born healthy. There are so many barriers to having them grow and develop in a healthy way. And I’m really passionate about taking babies from that point of birth to hopefully grow to be healthy children and adults. And so populations that are really at risk are in these low and low middle income countries where nutrition can be very poor and health care may be very minimal or even, you know, potentially basically nonexistent. And so my recent research has focused on newborns in these areas. And in 2019, I started the study that I’m still working on now, which is called preventing infant malnutrition with early supplementation or PRIMES. Mm-hmm. And the goal of PRIMES is was first to just look at how newborns grow. First, we define the newborn month as the first month after birth, and over that time, what people don’t always realize is that newborns typically lose weight before they start to grow. But how that happens in low and middle income countries had really not been described. So PRIMES started our project in Guinea Bissau and Uganda in 2019, following babies over the first 30 days, weighing and measuring them multiple times and asking their mothers about their health and their feeding to see if we could figure out how babies grow. Healthy babies grow in low and middle income countries and hopefully figure out what might be contributing to their poor growth.
Dr. Valerie Flaherman: [00:03:10] Yeah. And so we started in Guinea Bissau in Uganda, and we actually completed those projects in 2019. Mm-hmm. And it took a little longer to get started in our South Asian sites, which were in Karachi, Pakistan and in Douala account in Nepal. Ok. When we in Pakistan, we started in November 2019 and we actually were able to wrap up that first phase of the project by February 2020, not realizing what was right around the corner. But in Nepal, we started our project in December 2019 and they rolled it out a little bit slowly so that they had just finished enrollment of their target of 100 infants in mid-March 2020. Mm-hmm. And that’s when the shutdown started to roll across South Asia. So what we found is that the the plan for our study had been that we would weigh babies, weigh and measure them multiple times over the course of the first month. In addition to asking their mothers, how is their health, how are they feeding? How are they doing? You know, and what wound up happening is that we, our teams, were not able to actually go visit the mothers anymore because of the shutdown. So the mothers were not able to come to the medical center and the medical center teams were not able to go to the mother’s homes as planned to do these measurements. And so they were able to call the moms and just ask them, Are the babies sick or are they well? What’s happening, but we weren’t able to get those crucial measurements.
Lucia Arico-Muendel: [00:05:06] That must have been challenging. Ok, wow. Very interesting stuff, so I’m just curious about some crucial steps in the research process. So you are interested in lower and middle income countries. How did you settle on Uganda, Guinea-Bissau, Nepal and was it Afghanistan? Pakistan?
Dr. Valerie Flaherman: [00:05:31] Yeah, I think I think there were like a few. A key reason was that these teams had the the skills and infrastructure to access this population because our research actually involved enrolling and weighing babies when they were less than six hours old. Right. So to be able to to contact mothers in that very early time after birth requires a really specialized team that not only has the skills to even hold the baby that age, right, because that’s like a skill by itself, but also have the connections at the birthing facilities. Or in some cases, they were very. You wouldn’t really call it a health care facility, it would be maybe a health care worker in a room to have the connection and the trust with that person that they would be able to recruit someone in that very vulnerable time. And and because that work is really difficult to do, almost all the research on newborn weight in low and middle income countries will do something like they’ll report a newborn weight that happens sometime in the first month, or maybe if you’re lucky, sometime in the first week. But the thing is, babies actually on average.
Dr. Valerie Flaherman: [00:07:09] We now know now that we did times and looked at our data. They actually gain about 30 percent of their birth weight just over those first 30 days. And actually, before they gain weight, they actually start by losing weight. So on average, they lose seven percent of their birth weight. And then if you think about it, they basically gain thirty seven percent because they have to regain their seven percent to get back to birth weight, and then they end the month 30 percent up. So depending on when you weigh them there, if you’re trying to make if you’re trying to understand newborn birth weight and growth, if you’re not clearly specifying a time when you’re weighing them, you know your population is going to be, there’s going to be a lot of misclassification. So, so so the difficulty is, I think, why there was this lack of literature describing this time and and we were able to identify these teams that had the connections and had the skills to be able to approach to handle babies that approach moms at this early time. Ok.
Lucia Arico-Muendel: [00:08:22] So you partnered with a medical center in one city per country or multiple cities per country?
Dr. Valerie Flaherman: [00:08:31] Yeah, it was really well done in Uganda. We partnered with an academic team at Macquarie University that worked with three different health centers. Two were in Kampala, which is a very big, sprawling city. And one was in mono, which is sort of adjacent to Kampala. And then we had our collaborators in Karachi. Pakistan used two different hospitals in Karachi. One was an academic medical center that served a relatively more wealthy population and one was a public center, that health center that served a relatively more indigent population in Nepal. It was just the team was from that medical center and and recruited at their medical center. And then in Guinea Bissau, our team is non-medical. So these are really special people that Guinea-Bissau has particularly low levels of medical expertise. And a few people, I should say, not levels, but like the number of trained medical professionals is few and and so they have many different responsibilities that people that are trained medical professionals. So our team is non-medical but had developed the research skills needed to actually weigh and measure the babies. And they actually recruited from multiple different locations, including very small village health centers or even home births. Wow. So yeah, they are really, really special team.
Lucia Arico-Muendel: [00:10:31] So you really had a range of living experiences represented. Yes, across the different countries. That’s very cool.
Dr. Valerie Flaherman: [00:10:40] Very much so. Yes, in Karachi, we even had people that I think didn’t have any food insecurity or, you know, very protected. Part of that population was very protective. Interestingly, though, that population in Karachi still the newborns had still major problems with growth. In fact, that hospital maybe had, I believe, had the if I’m remembering correctly had the highest prevalence of underweight at at 30 days of age of any of the locations. Wow.
Lucia Arico-Muendel: [00:11:20] Fascinating. Yeah. Have you gotten to dig into that statistic a little bit like why it could be the case?
Dr. Valerie Flaherman: [00:11:27] Sure, I think part of it is their birth weight, the weight that they’re born, their actual birth weight because birth weight in our PRIMES study in the South Asian infants, birth weight was 200 grams lower than the African infants, and the African infants mean birth weight was 300 grams lower than U.S. infants have a mean birth weight of about 2400 grams.
Lucia Arico-Muendel: [00:11:55] Do you know what around what that is? In fact,
Dr. Valerie Flaherman: [00:11:57] It’s about seven pounds. Yeah, yeah, exactly. So that’s like the healthy baby. And in in Uganda, you know, and I don’t want to I always try to be careful not to sound like I’m making a statement about the whole country because we only enrolled about two hundred babies in Uganda. Two hundred babies in Guinea Bissau. So this does not represent the countries or their birth, but mean birth weight was 30 100 grams for those babies. And then in South Asia, it was two thousand nine hundred grams. So that’s mean birth weight. So at birth, many, like almost half of the population that we enrolled in South Asia, was already low birth weight at the time they were born. So really, they were already behind the curve, you know, at the time of their birth. Ok. And what we also saw was that especially in South Asia, for some reason, male infants are supposed to grow faster than female infants. Hmm. But for whatever reason, in South Asia, they actually didn’t seem to grow that much faster. And so since the World Health Organization child growth standards set range for normal growth that where the males grow much faster than the females, right? The South Asian males were very, very likely to be below the World Health Organization child growth standards at 30 days of age. So really not wanting to extrapolate too much to the whole country, but it did look like there are really important issues that need to be addressed.
Lucia Arico-Muendel: [00:13:56] Yeah, definitely. Definitely. Ok, see a few more questions about just how you get a study like this started, because it’s it’s just so exciting to think about how how do you select the specific mother infant pairs to participate? I guess I have a little a small sense of this because I worked on the service.
Dr. Valerie Flaherman: [00:14:23] Oh yeah, yeah.
Lucia Arico-Muendel: [00:14:25] So it sounds really difficult, you know, sort of filtering out the babies who can’t participate for whatever reason. Would you mind explaining a bit about that?
Dr. Valerie Flaherman: [00:14:38] Yeah, I think that the key as you select your methods and be, you want, you want to make sure that you you make a plan in advance that selects them rather than just using the least scientific thing is for someone to just use their judgment at the time when the baby’s born. Because when people do that, sometimes they think like, Oh, it’s almost lunch time. I don’t want to enroll this baby, or, Oh, I’m bored now, I’ll enroll this baby. And that’s a really non-scientific way to select your population. So you want to make sure that you have, like, very clear criteria in advance. Definitely. And for for the study that I was just talking about, we tried to have very broad entry criteria for that particular study. We any baby two kilos are up. We would who was we would enroll unless they were acutely ill at the time of birth. So if they obviously if a baby is sick and needs medical care, we don’t want to be weighing and measuring them and stuff like that. We want them to get the medical care they need. But what we did with that project is we took that information and we designed a randomized trial of an intervention to improve feeding. And for that, as you were mentioning, we picked some really careful criteria. Hmm. And one of the most important is that in this intervention, we’re studying the use of formula and whether it get a little bit of formula can help breastfeeding infants grow better, right? And so. If when we think about giving formula to babies in low and middle income countries, one of the key issues is that we should never give formula to babies when their mothers are HIV positive because formula and breastfeeding to get me to actually let me take a step back.
Dr. Valerie Flaherman: [00:16:48] So in the U.S., if a mother is HIV positive, if, if, if she’s on effective antiretroviral therapy and her viral load is is undetectable, some mothers actually decide to go ahead and breastfeed. And that’s a whole separate question. There’s been a lot of work done on that. But in the U.S., it would very much be an option for an HIV positive mother to not breastfeed and give only formula. And if a mother does that, the baby does not get HIV. It’s it’s basically impossible, right? Because HIV, you know, is not you can’t you can’t infect someone through just hugging them or kissing them. Something has to be like breastfeeding or like some kind of, you know, bodily more bodily fluids. Yeah. So so Formula I formula can be a very good choice for HIV, but babies of HIV positive moms. But in in the settings where we’re working in Africa, it our populations really can’t afford formula as like a substitute for breast feeding. Ok, so they would have to breastfeed with formula, and that is something that we really discourage for babies of HIV positive moms because combining breast combining breastfeeding from an HIV positive mom with formula actually makes it much more likely for the baby to get HIV. So we really don’t want to do that. So that was a major exclusion criteria for our our trial.
Lucia Arico-Muendel: [00:18:37] So mothers with HIV were excluded entirely.
Dr. Valerie Flaherman: [00:18:41] Ok? Yes, yes. And I think I think that is whenever you exclude a population, you have to think to yourself, is it ethical to exclude these people because we know that mothers with HIV are their children are at risk, right? We know their risk of health problems of not growing. But this particular trial is studying formula, which is an intervention that we specifically think will be not healthy for babies of HIV positive mothers. So I would love to to, uh, to go back to some of the populations that we’ve worked with and see if we can think of interventions that are effective for these babies of HIV positive mothers. And you know, for me, I’ve just learned a lot from doing this work that in the future I might actually design a different study, but this is the study we’re doing now. So you have to do it as ethically as you can.
Lucia Arico-Muendel: [00:19:49] Absolutely. Yeah. So going off of that, well, I guess first, what what aspects of the study of the infant and mothers lives did you control? What were the treatment groups? And then, yeah, what were the ethical considerations that come that came along with that?
Dr. Valerie Flaherman: [00:20:11] Yeah, yeah. I mean, I think so. There were two. Our study has two treatment groups and babies get mothers and babies get randomly assigned to one or the other. Mm hmm. One treatment group is recommendation to breastfeed exclusively, and exclusive breastfeeding is the standard of care. World Health Organization recommendation right now, right? Where really all around the world, unless there are very rare contraindications, the recommendation is that babies should get breast milk and nothing else other than vitamins, minerals and medications until they’re about six months of age when they can begin what’s called complementary feeding, which is typically like, you know, pureed meats or grains or fruits or vegetables or something, typically not formula or any kind of milk substitute and continue breastfeeding through one to two years of age, depending on there’s various not not total alignment of the guidelines about total duration of breastfeeding. Mm hmm. So that was one group. Mm hmm. And then the. The group had almost the same instructions to breastfeed exclusively, not use any other feeding, except the other group, which was the intervention group, was offered formula once a day for 30 days. Ok. Ok. And they could take as much as they well up to fifty nine miles, which is that’s two ounces. That’s actually a lot for for a newborn, you. So as much as they wanted up to fifty nine
Lucia Arico-Muendel: [00:21:56] Months, is that a typical bottle, half a bottle?
Dr. Valerie Flaherman: [00:22:00] It’s like I would say, it’s half of what you think of as a small bottle. Ok, like a small what you might think of as a small baby bottle with about four ounces. Ok, so behalf of that, but we actually had special bottles that are made for new. Ok, so they just contain the two ounces and you know, the babies would drink anywhere from just a teaspoon or a few sit sometimes, not sometimes. They weren’t hungry after breastfeeding. They drank nothing to drinking the whole bottle, and they would just do that once a day. Ok, so they were still getting most of their milk for breast milk, but a little something extra from that from the supplementary feeding.
Lucia Arico-Muendel: [00:22:45] I see. And was this formula that mothers in those countries would typically have access to? Or was it provided by your team?
Dr. Valerie Flaherman: [00:22:54] Yes, it was provided by the team from the United States, which I think is it’s that’s an issue that experts of all kinds often bring up because clearly a program is not sustainable, where it involves bringing in sealed bottles of formula from the United States to, you know, across the Atlantic Ocean, you know? But the the way our study was envisioned is as a pilot proof of concept study to see if if this would work. And one of the things that we’ve been very focused on is the concern that some of the scientific literature suggests that combining formula and breastfeeding might be riskier for infants in terms of causing more pneumonia or gastroenteritis. And the so we’re going to carefully be looking at all those results, the as we go forward and we have several kind of pre-specified time points to check the data and make sure that we’re not seeing anything concerning in that way. But that’s all part of the scientific process to do it rigorously and be very careful. Hmm. Yeah.