Institute Activities and Advances
Many organizational units within the NICHD conduct and support research in pharmacology to advance knowledge and improve treatments for various diseases and conditions within the Institute's mission.
The Obstetric and Pediatric Pharmacology and Therapeutics Branch (OPPTB) promotes research to improve the safety and effectiveness of medications for pregnant women and their fetuses and children. Recent studies include, but are not limited to, the following:
- Ibuprofen use for treatment of a congenital heart defect. NICHD researchers found that ibuprofen may be used to treat infants with patent ductus arteriosus. This heart defect occurs when the blood vessel (ductus arteriosus) that should close after birth stays open. This opening puts strain on the heart and increases blood pressure in the lungs.
- Multiple studies on the safety of medications during pregnancy include research on the use of clonidine to treat high blood pressure and the use of metformin for the treatment of diabetes.
The Pregnancy and Perinatology Branch (PPB) has recently conducted studies on:
- Prenatal steroids to improve survival rate in preterm infants. NICHD researchers found that prenatal steroids appear to boost survival and reduce brain injury in infants born as early as 23 weeks. This new finding may change the currentguidelines, which recommend these steroid hormones for infants between the 24th week and 34th week of pregnancy. These drugs improve the maturation of the lungs. Furthermore, in this study, 33% fewer deaths were reported than occurred using a comparison drug or placebo. In addition, those who survived had 20% fewer complications, from fewer cases of blindness and hearing problems to fewer developmental issues.
- New medication to reduce risk of preterm delivery. Studies conducted through the Maternaland Fetal Medicine Units (MFMU) Network resulted in approval by the Food and Drug Administration (FDA) of a new drug called 17 alpha-hydroxyprogesterone caproate (17P). A synthetic version of the hormone progesterone, this drug reduced the chance of women delivering early by about one-third. See the NICHD News Release FDA Approves Drug to Reduce Preterm Birth Risk for more information.
Researchers supported by the National Center for Medical Rehabilitation Research are studying pharmacologic therapies for patients with traumatic brain injury. Phases I and II clinical trials using single-drug therapy were unsuccessful, and researchers are now studying multiple pharmacological agents. Current studies include the combination of cyclosporine and dietary supplementation with choline and the use of vitamin D supplementation plus progesterone.
With support from the Contraceptive Discovery and Development Branch (CDDB), researchers may have discovered a compound that will lead to the creation of a nonsteroidal male birth control pill that causes nonpermanent sterility. Studies on mice were successful in inhibiting spermatogenesis and fertility using low levels of a compound that achieved male sterility in 1 to 2 weeks. The effects were reversible and removal of the compound resulted in the reversal of sterility.
Researchers in the Section on Growth and Obesity, part of the Division of Intramural Research, recently found that metformin, a diabetes drug known to decrease obesity and obesity-related comorbid conditions in adolescents, had similar effects on younger children. Children ages 6-12 years who were prescribed the medication had significant decreases in body mass index, body weight, and fat mass.
In addition, the Maternal and Pediatric Infectious Disease Branch supports a great deal of research on therapies related to reducing the spread of HIV. For example, the Branch's Therapeutic Research in HIV Infection in Infants, Children, Adolescents, and Pregnant and Non-Pregnant Women program evaluates the pharmacokinetics and safety of new medications.
In 2011, researchers supported by the Pediatric Trauma and Critical Illness Branch published research on cardiac protection for severely burned children. Severe burns over a large portion of a child’s body can speed up normal metabolic processes to alarming levels. This “hypermetabolic” response causes dangerous acceleration in a child’s heart rate and cardiac output, as well as other physiological problems that, unless checked, can interfere with the body’s ability to use oxygen, glucose, and other essential factors. Over time, young patients may experience losses in lean body mass, bone mineral content, and density, as well as nutritional problems that interfere with growth. The drug propanolol has been shown to decrease cardiac stress in children and to lessen other harmful effects of the hypermetabolic response, but little was known about how much of the drug was actually necessary to lower this pathological stress in young burn patients. Further, nothing was known of how a child’s distinctive physiology may affect drug action within the body, which would help guide dosing recommendations. To establish the correct dosing regimen for this important drug, scientists conducted a controlled clinical trial of propanolol in over 300 pediatric burn patients. Researchers established how much of the drug was necessary to lower pediatric burn patients’ heart rates by 15%. They determined that the drug acted quickly, achieving effective levels within 30 minutes to one hour. They also found that the dose should be increased significantly over the first 10 days to maintain the benefits of the treatment. (PMID: 20598332)
To better understand drug-resistant bacteria, a serious and growing threat to public health, researchers from the NICHD’s Cell Biology and Metabolism Program studied how a small protein interacts with a cellular pump known as AcrAB-TolC complex found in the common bacterium Escherichia coli.The three components of the E. coli AcrAB-TolC complex—AcrA, AcrB, and TolC—have been studied for their roles in multidrug resistance. This complex pumps out agents, such as drugs, that threaten the survival of bacterial cells. In addition to the complex, E. coli contains about 60 small proteins that scientists have not studied as closely. The roles of these proteins are largely unknown, but because the proteins have remained stable over time and function under certain conditions, scientists think that they have important roles in the cell. Researchers conducted a study to examine small proteins and found that a certain E. coli small protein (AcrZ), which is found in the inner membrane, interacts with the AcrAB-TolC complex and plays a role in resistance to antibiotics by helping to recognize and export certain drugs out of the cell. These findings lay the foundation for future research in determining how small proteins play a role in antibiotic resistance, which could then help scientists develop improved interventions to combat bacterial drug resistance. (PMID: 23010927)
Other Activities and Advances
To achieve its goals related to pharmacology research, the NICHD supports a variety of programs, networks, and centers to further research and to advance training opportunities.
- The Biological Testing Facility, funded by the CDDB, is currently studying more than 150 tests and procedures for the evaluation of new drugs, formulations, and delivery systems for research in contraception and reproductive health.
- The Obstetric-Fetal Pharmacology Research Units Network, supported by the OPPTB, provides expertise and infrastructure for conducting clinical trials of medications to treat conditions in pregnancy, such as gestational diabetes, severe nausea, high blood pressure, and preterm labor.
- The CDDB-funded Contraceptive Clinical Trials Network includes 12 research sites studying contraceptive methods and devices for women, and 2 sites for men. It focuses on preventing pregnancy and on reducing the spread of sexually transmitted infections.
- The OPPTB leads the NICHD's efforts related to the Best Pharmaceuticals for Children Act, which was passed to increase research on drugs used in children. The goal of the Act and of the Branch's activities related to the Act are to improve pediatric therapeutics through preclinical and clinical drug trials that lead to changes in drug labeling.
- The Pediatric Trials Network (PTN) program , initiated in 2010 and funded by the OPPTB, is an alliance of clinical research sites located around the United States that are cooperating in the design and conduct of pediatric clinical trials to improve health care for the youngest patients.
The Specialized Centers in Research in Pediatric Developmental Pharmacology, also funded through the OPPTB, began in 2010 with the goal of studying the safety and efficacy of medications from birth through adolescence, and providing research opportunities for scientists in this area. Currently, medications for Duchenne muscular dystrophy, pediatric cancer, retinopathy of prematurity, and bacterial infections in children are being studied.
- The PPB also supports the Maternal and Fetal Medicine Units (MFMU) Network. Established in 1986, the network focuses on clinical issues in maternal-fetal medicine and obstetrics, including maternal health, fetal health and development, gestational diabetes, asthma, thyroid disorders, and preterm labor including studies of pharmacology for treating or preventing these conditions.