Biology fascinates me. It is elegant and complex and high-stakes. It is highly conserved among all life on Earth, yet parts of it remain a mystery to us. Thinking about what it takes to actually create life and to sustain it provides some perspective on our place in the world.
But I never thought it would be so hard to actually participate in it. I’ve been studying biology now in some capacity for over a decade, and my experiences in research have run the gamut from molecular to landscape. I haven’t hit the ecosystem level yet, but I’m sure it’s coming. But far and away the hardest thing I have had to wrap my head and heart around has been my own participation in human reproduction. You see, I’m expecting my first baby in July, and pregnancy has been a cruel bitch. I was elated to find out I was pregnant. I think I danced on cloud nine for three solid days, rejoicing in the exciting news with my husband, Chris. We did the math, figured out the due date, and downloaded the app that every week gives you a fruit or vegetable to envision the relative size of your growing fetus. And we also check the Daddy-to-be edition, which dumbs the same thing down to common household items. You know, because men don’t know the size of an eggplant or a mango. The gendered stereotypes in pregnancy are real. But that’s not what this is really about. This is about how not all pregnancies are filled with “glow” and gentle fluttery kicks and the glorious buildup to the miracle of childbirth. Instead, my pregnancy has been a (so far mostly successful) battle with Hyperemesis Gravidarum—or HG for short. I knew HG existed, having watched my good friend battle the same condition during both of her pregnancies. I was a 22 year old kid, fresh out of college, without an inkling of thought for family planning aside from prevention, and I vividly remember her lying on the floor of our back office moaning that she felt so shitty. She brought oatmeal to work for dinner, and barely picked at it. But Matteo was born, strong and healthy, and she bounced back quickly. During her second pregnancy, I covered for her at work for many weeks when she had to go to the emergency room for fluids and electrolytes. And then Diego was born and he was strong and healthy, too, and she was fit as a fiddle and back at work in no time. And selfishly, I never thought that the same would happen to me. Only about 60% of pregnant women have any nausea at all, and many of them don’t ever throw up. For those who do, the vast majority of them feel much better after the rapid embryonic growth and development of the first trimester. HG pregnancies account for only about 0.5% of live births. The illness is characterized by extreme vomiting, sometimes lasting the whole pregnancy, that in mild cases results in weight loss and dehydration and in severe cases can cause extreme nutritional deficiencies and even maternal death. HG is loosely associated with low birth weight, preterm labor, and potential behavioral conditions, but on the whole, it is a disease of the pregnant mother. High levels of human chorionic gonadotrophin (hCG) are to blame for standard morning sickness, known more accurately as “nausea and vomiting of pregnancy”. hCG is the hormone you test for with a pregnancy test. It is produced by the developing placenta and peaks at around 12 weeks. At this point, there is very limited blood flow from the mother to the baby, but the hCG coming from the placenta plays a vital role. Maintaining a pregnancy requires elevated levels of progesterone, which will eventually come from the placenta. However, in early pregnancy, the placenta is neither big nor vascular enough to produce enough progesterone, which means the corpus luteum—which is formed on the ovary after a follicle ovulates—needs to pick up the slack. In the absence of pregnancy, the corpus luteum will stick around for about a week, and when it starts to deteriorate, progesterone levels fall, which leads to menstruation. Most women know and appreciate that that’s the body’s sick sense of revenge for not getting pregnant every month. But my bigger point here is that we understand how these general things work. The hormone profile changes are predictable and can be used to successfully diagnose pregnancies, predict risk for miscarriage, and otherwise assess a woman’s reproductive health. When it comes to HG, we don’t know any these things. According to the one published literature on hyperemesis, Valberg et al. (2005) say point blank that “both the aetiology and pathogenesis of HG remain unknown.” This is fancy doctor speak for we don’t know the cause of the disease (aetiology) or how it is developed (pathogenesis). They’ve studied all the common steroid hormones, as well as others like leptin, prolactin, and those produced in the thyroid gland, and nothing has been shown to be conclusive. In short, we have no idea. More frustratingly, there doesn’t seem to be much interest in actually figuring it out. I searched far and wide for a team working on tackling this problem, and while one researcher at UCLA has committed to focusing on HG, the published literature is sparse. Instead, teams are conducting small, retrospective studies with findings that are correlative at best and inherently biased at worst (McCarthy et al. 2014). Given that HG costs for care and treatment tally up to over $200 million a year in the US alone, and that it affects women of all socioeconomic and racial backgrounds, why haven’t we figured out what causes it? Given what I’ve read and what I’ve experienced, I’ve got a few musings on that question. Firstly, HG was thought of as a psychological condition until only a few decades ago. Women were accused of using it as an excuse to avoid sex during pregnancy and some crazies even suggested it was an unconscious way of women trying to expel unwanted fetuses. It’s not just in cases of HG where women’s complaints of pain and suffering have been undermined. Conditions such as fibromyalgia are notorious examples of women being told they were making it all up, only to have advancements in neurological sciences corroborate the excruciating pain of overactive nerve endings. In my own experience, people expect pregnant mothers to be so over-the-moon at their pending bundle of joy that they’re willing to be that sick for that long. But people don’t really get it—HG is not one singular sickness event or occasional nausea. It is relentless, stomach-clearing illness. There were periods during my first trimester when I couldn’t keep even a sip of water down for more than a few minutes, and I went for days without holding down any food. It has landed me in the emergency room once, but many women are in and out of the hospital for their entire pregnancies. And it’s not uncommon for women to be denied medication to treat the nausea. For decades, Zofran was the drug of choice for treating HG. For me, it has been a saving grace. But a study came out not too long ago, hinting that maybe in some cases it could cause heart defects. Rather than take these admonitions at face value, I read the paper. The paper investigates over 1.5 million births, of which 43,658 infants had congenital heart defects. Sounds impressive, but that’s not really what the paper is about, since the title is “Use of ondansetron during pregnancy and congenital malformations in the infant”. Of these 1.5 million births, only 1349 (yes, less than 0.08%) were exposed to Zofran (ondansetron is the generic name). The study doesn’t say whether these 1349 infants come from the full population of studied infants, or only from those with malformations, and this omission seems crucial. If the infants exposed to Zofran come from the entire population of 1.5 million babies, the statistical methods do not offer evidence of a control. If they come from the 43,658 infants with identified heart defects, the researchers are preemptively searching for foregone conclusions. Furthermore, the authors directly state that their “data do not support the idea that use of [Zofran] in early pregnancy is associated with a high risk of congenital malformations” but go on to say that “a risk …may exist and we suggest the drug should not be used…for nausea and vomiting in early pregnancy until further large prospective studies are available” (Daniellson et al. 2014). This is an unacceptable level of scientific pandering. Women who have HG and are taking Zofran for treatment of severe nausea and vomiting during pregnancy do not always have the time or the skills to weigh these kinds of guarded phrases. Furthermore, the nutritional deficiencies that arise from HG in early pregnancy might themselves be the cause of some of these conditions that are being correlatively linked to Zofran use (Fejzo et al. 2010). More problematic is the fact that these “findings” become weapons used against women who have their babies’ best interests at heart. I tend to stay off the Mommy Groups, but I’ve had my share of people questioning whether taking medicine to control my HG is safe for the baby or saying things like “I could never do that to my baby.” Many doctors and midwives use that study as leverage to refuse women prescriptions for Zofran, even when their medical need is severe. In fact, a recent (and empirically robust) study out of UCLA found conclusively that babies whose moms need Zofran to treat HG do just as well as babies whose moms don’t have HG and do comparably better in terms of birth weight and overall health than those whose moms have untreated HG (Fejzo et al 2016). Medicine works, and in general I believe that it solves more problems than it creates, but the guilt trips are strong in the Mommy Realm. I count myself lucky that I have the skills and the access to go to the primary literature and make decisions for myself, and that consequently I expect my doctors to be accurate in their interpretation of the science. But there’s an even better way to address this problem. The answer (as I usually propose) is more, better science. More than just trying to correlate cases of HG with certain demographics or ages or sexes of babies, we need to know what combination of hormones or microbes or antibodies is responsible for causing such devastation. By asking these ultimate questions, we can develop therapies that actually treat the causes of HG, not just the terrible symptoms. My faith in science is strong; with good methods and appropriate support, there’s nothing that evades our capacity to figure it out. HG, as well as many other pregnancy-related conditions, is worth figuring out. In this day and age, the excuse that women have always been dealing with HG or morning sickness or whatever ailment pregnancy throws at them is unacceptable. It doesn’t matter that the disease or discomfort itself may only last for a few weeks or a few months at a time. We have more women in the sciences than ever before, and we have advanced technologies and brilliant researchers who can solve this problem. We need to reframe the way we think about pregnancy. After all, just because something’s always been done that way doesn’t mean the status quo is the solution. High-quality science, effective communication, and a commitment to research-based best practices serves everyone. By understanding and promoting maternal health, we by default support healthy babies and healthy families. So, I’m excited to meet my baby, who I already love and sacrifice for. And I’m also excited to move past this HG, but I hope I don’t forget about it. Being aware of the problem is the first step towards solving it. So yes, I have HG, and yes I expect that in the end it will “all be worth it when I meet my baby”, but I also have hope. I have hope that we can stop judging women who suffer and struggle with pregnancy and instead support and nurture each other. I also have hope that we can employ good science to help move past the conversation to actual research-based therapies instead of telling women like me to just drink some ginger ale and get over it. References: Danielsson B, Wikner BN, Källén B. 2014. Use of ondansetron during pregnancy and congenital malformations in the infant. Reproductive Toxicology 50:134-137. Fejzo MS, Poursharif B, Korst LM, Munch S, MacGibbon KW, Romero R, Goodwin TM. 2010. Symptoms and pregnancy outcomes associated with extreme weight loss among women with hyperemesis gravidarum. Journal of Women’s Health 18(12):1981-1987. Fejzo MS, MacGibbon KW, Mullin PM. Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States. Reproductive Toxicology 62:87-91. McCarthy FP, Lutomski JE, Greene RA. 2014. Hyperemesis gravidarum: current perspectives. International Journal of Womens Health 6:719-725. Verberg MFG, Gillott DJ, Al-Fardan N. Grundzinkas JG. 2005. Hyperemesis gravidarum, a literature review. Human Reproduction Update 11:527-539.
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