Exactly 10 weeks before her due date, Shannon Frick woke up bleeding. She was scared, but, by now, she was used to being scared. Her entire pregnancy had been fraught with terror. Although Shannon initially conceived twins, one baby boy died in utero when she was 18 weeks pregnant. Survival was far from certain for his brother because Shannon맥스카지노�s body wasn맥스카지노�t making enough amniotic fluid. 맥스카지노�We had been told that if he made it to birth, there would be an 80 percent chance of severe neurological and pulmonary defects,맥스카지노� recalls Shannon, who is now 34 and lives with her family in Holden, Massachusetts. 맥스카지노�It was devastating. We were grieving the loss of one baby and having to think about how far we would go to save this one.맥스카지노�Shannon rushed to the University of Massachusetts Memorial Hospital, where her bleeding was diagnosed as a partial placental abruption, a condition in which the placenta rips loose from the uterus, which can be fatal for both mother and child. Liam was delivered via emergency Caesarean section at 30 weeks gestation. He weighed just two pounds, 10 ounces, but he was breathing on his own. The baby was whisked away to the neonatal intensive care unit (NICU) before Shannon got a chance to hold him. Still, she and her husband, Michael, allowed themselves to hope. But, within a few hours, Liam began struggling for air. Doctors rushed to put him on a ventilator, and then a high-frequency oscillator, a kind of souped-up ventilator that forces air into a patient's lungs by shaking them violently. The baby맥스카지노�s oxygen continued to drop. Shannon was still in her recovery room when a neonatologist came in to explain that Liam맥스카지노�s circulatory system wasn맥스카지노�t adapting well to life outside the womb; his blood pressure was spiking and his heart rate was erratic. Shannon is a nurse, so she was aware of the risks of this condition, known as persistent neonatal pulmonary hypertension. 맥스카지노�That term scared the ever-living hell out of me,맥스카지노� she says. 맥스카지노�I asked the doctor, 'Are you sure you can handle this?'맥스카지노� 맥스카지노�I know I can,맥스카지노� the neonatologist told her. But they would need to try treating Liam with nitric oxide, an inhaled medication that relaxes muscles in the lungs to improve respiratory function. The doctor explained that the Food and Drug Administration had approved nitric oxide for use in full-term babies—but it wasn맥스카지노�t approved for preemies like Liam. There just wasn맥스카지노�t enough data to go on. The FDA doesn맥스카지노�t regulate a doctor맥스카지노�s ability to prescribe drugs to an unapproved patient population, but going 맥스카지노�off label맥스카지노� would mean they had no idea of the potential side effects or complications. Then he added: 맥스카지노�But if we don맥스카지노�t do it, Liam probably won맥스카지노�t live through the next 24 hours.맥스카지노� Shannon didn맥스카지노�t hesitate. 맥스카지노�I don맥스카지노�t care that it hasn맥스카지노�t been tested,맥스카지노� she said. 맥스카지노�If my other option is walking out of this hospital without a baby, we need to do it.맥스카지노� Their gamble appeared to pay off. Liam began to stabilize over the next few hours, and he was able to wean off the ventilator four days later. But the next morning, an X-ray showed that the baby had developed a small brain bleed. Shannon and Michael knew it was likely a nitric oxide side effect. They looked at each other over Liam맥스카지노�s incubator, both thinking the same thing: Oh God. This is our fault. The Fricks were working off little information, but they were lucky to know as much as they did about their doctor맥스카지노�s decision. 맥스카지노�Neonatalogists and pediatricians have become so accustomed to prescribing a drug off-label, they hardly even think about it,맥스카지노� says Robert Ward, M.D., emeritus professor and former director of the University of Utah School of Medicine맥스카지노�s pediatric pharmacology program. 맥스카지노�And they usually don맥스카지노�t tell the parents what they맥스카지노�re doing.맥스카지노� That맥스카지노�s because 90 percent of the medications used in NICUs, as well as the majority used across all pediatric medicine, have never been tested for safety or efficacy in babies, especially those born before full gestation. If doctors stuck solely to on-label prescribing, they wouldn맥스카지노�t be able to treat most of the patients admitted to their care. Liam recovered from the brain bleed. But Shannon and Michael couldn맥스카지노�t stop asking each other: Did we do the right thing? There was no way to know for sure. Liam spent 10 weeks in the hospital맥스카지노�s NICU. Now 3 years old, he is small for his age, continues to have respiratory issues, and is still catching up on speech and other milestones. 맥스카지노�But he맥스카지노�s here,맥스카지노� says Shannon today. Without the nitric oxide treatment, she맥스카지노�s sure he wouldn맥스카지노�t be. Yet she맥스카지노�s still shaken by their high-stakes decision. 맥스카지노�Why isn맥스카지노�t this medication studied so it can be approved for use in these babies?맥스카지노� she says.We're used to thinking that the United States offers the most cutting-edge healthcare in the world, yet countries like Lithuania and Bosnia have a lower infant mortality rate than we do. While the reasons for that are complex, a prime one is a higher rate of illness at birth. And our renowned medical experts are often working on their tiniest, most vulnerable patients without a net—relying on little more than raw intuition about which medicine to prescribe.The FDA hasn맥스카지노�t approved a new drug specifically for neonatal use in 17 years. Christina Bucci-Rechtweg, M.D., head of pediatric and maternal health policy for Novartis Pharmaceuticals, is quick to acknowledge the 맥스카지노�desperate need맥스카지노� for better research on pediatric drugs, but she맥스카지노�s also blunt about why it맥스카지노�s not happening: money. 맥스카지노�This makes me sad to talk about, but it맥스카지노�s very expensive to develop a therapy that맥스카지노�s only a very small population,맥스카지노� she explains. 맥스카지노�You might not see a return on your investment, been one of the main things keeping industry away from this field.맥스카지노� In other words: You can sell erectile dysfunction drugs to tens of millions of adult men, but there맥스카지노�s no profit in medications that save the lives of a few hundred thousand preterm babies. 맥스카지노�It breaks my heart,맥스카지노� says Shannon. 맥스카지노�We맥스카지노�re talking about tiny, little humans who have done nothing wrong but might not get a fighting chance because companies don맥스카지노�t support this research.맥스카지노� And because companies are reluctant to invest in new drug research, most of the drugs used in NICUs today are older and off patent, meaning any manufacturer can make them. Pharmaceutical companies profit off new drugs, which they can patent and sell exclusively for three to seven years, according to FDA regulations. So there맥스카지노�s no financial incentive to get better safety data on older drugs, when companies are already selling them as cheaply as possible. But advocates for neonatal drug research argue that the pharmaceutical business model shouldn맥스카지노�t trump public-health math. When a healthy baby leaves the NICU, the cost of his or her treatment can then be amortized over a 70-year lifespan—while treating the heart condition of a 60-year-old will extend their life by maybe 10 or 15 years, tops. 맥스카지노�I맥스카지노�ve tried to make the case to both drug companies and the FDA that the lifetime impact should elevate the importance of this research,맥스카지노� says Francis Sessions Cole, M.D., director of the division of newborn medicine at the Washington University School of Medicine in St. Louis, Missouri. But pharmaceutical companies aren맥스카지노�t as interested in 6-month-olds who are decades away from being a part of the larger drug-buying public. 맥스카지노�The argument doesn맥스카지노�t wash when there맥스카지노�s no money to be made,맥스카지노� Cole notes. 맥스카지노�And yet these babies are all unbelievably sick, and we need to do something.맥스카지노�When we don맥스카지노�t, the worst can happen. In 2006, three premature babies died in a single week after they were accidentally given adult-sized doses of heparin, a blood thinner used to flush catheters and prevent blood clots, at Methodist Hospital in Indianapolis, Indiana. The FDA notes that the safety and efficacy of heparin in pediatric patients 맥스카지노�has not been established,맥스카지노� and even includes a specific warning about the special risks it can pose when used in newborns. (News outlets reported that adult-sized doses of the drug had mistakenly been stored in the NICU맥스카지노�s drug cabinet; the hospital issued a statement offering to provide counseling and restitution to the families.)These kinds of horror stories are why Rob and Alicia Furman of Raymore, Missouri, were anxious every time a medication arrived in the NICU for their daughter. Briella was born at just 23 weeks gestation on March 28, 2016, at Saint Luke맥스카지노�s Hospital in Kansas City, Missouri, weighing only 12 ounces. 맥스카지노�We were lucky to be at the only hospital in our area that stocks small enough breathing tubes,맥스카지노� says Rob. 맥스카지노�If we맥스카지노�d been somewhere else, they might not have even tried to resuscitate her.맥스카지노� Nearly every one of the 156 days Briella spent in the NICU brought a new fight to keep her alive. Every time the Furmans asked Briella맥스카지노�s doctors about the potential risks of a treatment, they say they received the same unsettling answer: 맥스카지노�There맥스카지노�s just no research on that.맥스카지노� The powerful opiate fentanyl was one under-researched drug prescribed to Briella for pain management. Fentanyl is not FDA-approved for use in patients under age 2 because there are no studies establishing its safety and efficacy, and the Furmans were alarmed to see the hospital pharmacy send the drug over in an adult-sized, 50-cc syringe. "The dose for Briella was only half a cc," says Alicia. "Our medical team was incredible, but every time they gave it to her, I thought about how it would be so, so easy to mis-dose these tiny babies."That맥스카지노�s assuming doctors know the right dose to give in the first place. Every morning, Malgorzata Michalowska-Suterska attends rounds in intensive care units of Maria Fareri Children맥스카지노�s Hospital at Westchester Medical Center in Valhalla, New York, where she works as a clinical pharmacy specialist. Residents balance laptops and coffee mugs; attending physicians study X-rays and fire off questions. Michalowska-Suterska follows with an iPad, making meticulous notes about every change in a patient's medication list.Often a doctor will pause to ask her which type of diuretic or mood stabilizer Michalowska-Suterska thinks would be the best match for that particular child. All she can do is make her best guess.맥스카지노�When my colleagues come over from the adult side of the hospital, they can맥스카지노�t believe this is how we do things,맥스카지노� she says. 맥스카지노�When an adult is put on a new medication, we know how well it will work because we have these wonderful randomized, placebo-controlled, double-blind studies done on 2,000 patients.맥스카지노� She맥스카지노�s referring to the 맥스카지노�gold standard맥스카지노� research trials required by the Food and Drug Administration for any new drug to hit the market: Large rosters of patients are randomly assigned to groups that receive either the medication in question or a placebo as a control. The trials are known as double-blind, because neither patients nor doctors will know which pill they맥스카지노�re taking, which lets researchers analyze their results without bias. If patients taking the drug fare better than patients taking a placebo (while meeting other study targets, like a low rate of side effects), the drug is likely to be approved for use in patients like those in the study.Meanwhile, in the pediatric wards: 맥스카지노�We have case reports with two patients,맥스카지노� says Michalowska-Suterska. 맥스카지노�Or very small studies. If you can find a trial with 15 patients, you think, Wow, this is great.맥스카지노� When a doctor asks her to recommend a drug, she looks at research done on adults, and then estimates how to titrate a dose for a one- or two-pound preemie. But estimates only get you so far. About one third of infants experience what doctors and pharmacists euphemistically call a pharmokinetic surprise, where they develop side effects not usually seen in adult patients—or the drug simply doesn맥스카지노�t work because the dose wasn맥스카지노�t strong enough, says Matthew Laughon, M.D., a neonatologist and professor of pediatrics at the University of North Carolina at Chapel Hill. This 맥스카지노�surprise맥스카지노� rate is so high because babies are not tiny adults: Every system in their body is still developing, and they circulate and metabolize drugs in unpredictable ways. Whether you맥스카지노�re 20, 40, or 60, an adult's kidneys clear drugs out of the body in more or less the same way—and much more effectively than the still-developing kidneys of a newborn. 맥스카지노�When you맥스카지노�re talking about babies born 10 or 14 weeks early, maturation after birth is unpredictable,맥스카지노� says Laughon. The Furmans say they understand why most of the medications given to baby Briella had no relevant research: 맥스카지노�The odds of survival when you맥스카지노�re born at 23 weeks are just 25 percent,맥스카지노� says Rob. 맥스카지노�Even if you could find four babies like her to study, three of them aren맥스카지노�t going to make it. There goes your data.맥스카지노� Every year, only 500,000 infants are born prematurely in the United States. When you start sorting them by medical diagnoses, the lists get even shorter. In addition to slicing into drug company profits, that makes it hard to find a truly representative sample of babies with the same type of congenital heart defect, or the same type of postnatal respiratory issue. And many parents are understandably skeptical about the premise. Ward recalls trying to study methadone as a painkiller in newborns; he knew from preliminary data that it has fewer side effects than many other pain medications. But over three years, he was only able to recruit seven children to participate in his study. 맥스카지노�Parents would literally back away from me,맥스카지노� he says. 맥스카지노�They would say, 맥스카지노�That will make my child an addict.맥스카지노�맥스카지노� Researchers also have to decide how to control for a long list of variables: How was the mother맥스카지노�s prenatal health care? What other drugs has the infant received? And they have to decide on a reasonable end point to the research—a difficult task when the goal is to save a baby맥스카지노�s life and give them a relatively normal lifespan. 맥스카지노�We맥스카지노�re always asking, how long is long enough?맥스카지노� says Jonathan Davis, M.D., chief of newborn medicine at the Floating Hospital for Children at Tufts Medical Center in Boston. Depending on the drug, researchers may need to follow their trial subjects for years to show that a medication given at birth doesn맥스카지노�t impact how they learn to walk, talk, or do long division. And the longer a study runs, the more expensive it becomes. Of course, physicians and pharmacists can draw on their own clinical experience for these decisions. Shannon Frick says she felt reassured when Liam맥스카지노�s neonatologist revealed he had successfully used nitric oxide in a baby with similar problems just the week before. But a doctor맥스카지노�s anecdotal experience always involves a smaller sample size and a higher degree of confirmation bias than a well-run trial. And when researchers are finally able to look closely at frequently used drugs, they often discover problems. Laughon points to cisapride, a medication used to treat gastric reflux by moving stomach contents along the digestive tract, which was removed from the market after decades of use when a study finally revealed that it could cause sudden death in babies. 맥스카지노� multiple situations where we맥스카지노�ve gone back to study drugs after we맥스카지노�ve used them and found out that, lo and behold, they맥스카지노�re really not safe,맥스카지노� says Davis. 맥스카지노�And it맥스카지노�s shame on us that we didn맥스카지노�t really study it in the first place.맥스카지노�Davis has been fighting for those studies for most of his career. He now chairs the Neonatal Advisory Committee for the FDA맥스카지노�s Office of Pediatric Therapeutics, implementing what he calls 맥스카지노�a system of carrots and sticks맥스카지노� created as a result of several laws passed over the past 15 years and made permanent under the FDA Safety and Innovation Act of 2012. The 맥스카지노�carrot맥스카지노� dangled before pharmaceutical companies is a six-month extension on the exclusivity of any new drug patent if they study the drug in pediatric patients. 맥스카지노�An extra six months on patent can translate to millions of dollars in exclusive sales,맥스카지노� says Ward. 맥스카지노�That can more than offset the cost of the research.맥스카지노� The 맥스카지노�stick맥스카지노� is that the FDA can now require drug makers to study a medication in children any time they submit an adult application. And they have to consider testing their new drugs specifically in newborns (not just older kids, who are easier and cheaper to study). 맥스카지노�If you맥스카지노�re not studying the drug in a neonatal population, you have to be able to say why on your application,맥스카지노� says Susan McCune, M.D., director of the FDA맥스카지노�s Office of Pediatric Therapeutics. As a direct result of this legislation, 675 medications have had their labels updated to reflect new research on the correct dosing guidelines for pediatric patients. But only a fraction of those drugs will help treat newborns, counters Ward. The rest are geared toward older infants and children. He and many others argue that the current regulations don맥스카지노�t go far enough. 맥스카지노�To some extent, the law has prompted drug companies to focus on developing drugs that don맥스카지노�t have any use in children,맥스카지노� says Cole. 맥스카지노�That lets them avoid the issue all together.맥스카지노� Bucci-Rechtweg of Novartis doesn맥스카지노�t disagree: 맥스카지노�The diseases of neonates pretty much don맥스카지노�t exist in adults,맥스카지노� she says. 맥스카지노�Very few new adult therapies are being developed that may the neonatal population.맥스카지노� But while the pharmaceutical industry parses their legislative mandates for loopholes, babies in every NICU and PICU in the country are being injected with under-researched medications. After Rachel Thomas맥스카지노�s water broke while 16 weeks pregnant with her son Zachary, she spent the next 10 weeks on bed rest, trying to stave off labor. 맥스카지노�I was advised to have an abortion, because the odds of his survival were so grim,맥스카지노� she says. 맥스카지노�We were in a world of hell.맥스카지노�Zachary was delivered via C-section at Inova Fairfax Hospital in Falls Church, Virginia, 14 weeks before his due date, and immediately taken away for intubation. Like Shannon, Rachel hadn맥스카지노�t even held Zachary when she was asked to consent to the use of nitric oxide within hours of his birth. Zachary stabilized on the ventilator but wasn맥스카지노�t able to breathe on his own; within a few days, his kidneys began to shut down. A doctor took Rachel and Chris aside and explained that there were drugs they could try. 맥스카지노�But you should know your rights as parents,맥스카지노� he added. 맥스카지노�If at any point you don맥스카지노�t want us to continue, it맥스카지노�s your right to tell us to stop and just give you time to hold him.맥스카지노� It was the moment that Rachel had spent her whole pregnancy trying not to imagine but knew would probably come—when she and Chris had to decide whether to keep fighting to save their baby or let him die in their arms. She looked at Chris and then at the doctor. 맥스카지노�Whatever drug you need to give him, just do it,맥스카지노� she said. "We're going to throw the kitchen sink at this.맥스카지노� During the seven months he spent in the hospital맥스카지노�s NICU, Zachary was prescribed 40 different drugs.Three years later, Rachel can맥스카지노�t remember which combination the doctors tried to treat her baby맥스카지노�s kidney failure—but she does remember feeling numb with relief when Zachary finally wet his diaper, a sign that his kidney function was returning. It was one of many days when she left his incubator to go to the NICU맥스카지노�s private breast pumping room and cry. 맥스카지노�When the decisions are that black or white, you don맥스카지노�t think about side effects or long-term risks,맥스카지노� she says now. 맥스카지노�And it맥스카지노�s hard to explain the fog we were moving through in those first few weeks; I was trying to stay in this positive state of denial to make it through my pregnancy, and now that was all crashing down.맥스카지노� She was recovering from a C-section, pumping breast milk around the clock, and trying to figure out how to be a mother to a baby she could barely touch. Now, when Rachel wades through the long list of Zachary맥스카지노�s prescriptions, she says, 맥스카지노�Most of these, I never even knew he was given.맥스카지노�That may be the crux of the matter. Parents thrown into catastrophic infant health crises need to feel informed and able to trust their medical teams to make evidence-based decisions. But they맥스카지노�re also operating through a haze of fear, exhaustion, uncertainty and grief—and they don맥스카지노�t know what they don맥스카지노�t know. 맥스카지노�I don맥스카지노�t parents upfront that there are major gaps in our understanding of drug metabolism in babies,맥스카지노� says Cole, noting that he doesn맥스카지노�t usually share that information until a baby experiences an adverse effect. 맥스카지노�Then we retroactively explain that we did this based on the best information we had.맥스카지노� The right information will require years of new research and millions of research dollars. In the meantime, hundreds of thousands of kids like Liam, Briella, and Zachary are growing up as survivors—the tiniest of babies who overcame incredible obstacles. 맥스카지노�But beating these kinds of odds comes with a price,맥스카지노� says Rachel. Four years later, Zachary is a sweet, curious boy. But he맥스카지노�s just beginning to speak in complete sentences. He also struggles with low muscle tone and significant feeding and motor-skill delays. Rachel often wonders which of her son맥스카지노�s challenges are related to his early birth, and which could be the lingering consequences of all of those drugs that saved his life. 맥스카지노�I mean, something caused these things,맥스카지노� she says. 맥스카지노�But I맥스카지노�ll just never know.맥스카지노�