MOMS Trial

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The MOMS Trial was a clinical trial that studied treatment of a birth defect called myelomeningocele , which is the most severe form of spina bifida. The study looked at prenatal (before birth) and postnatal (after birth) surgery to repair this defect. The first major phase concluded that prenatal surgery had strong, long-term benefits and some risks. [1]

Contents

The name of the trial stands for Management of Myelomeningocele Study. It was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and was done by The Children's Hospital of Philadelphia, the University of California, San Francisco, Vanderbilt University Medical Center in Nashville and the George Washington University in Washington, D.C.

Introduction

Spina bifida, or myelomeningocele, is a type of open neural tube defect that can occur with problems with the early development of a fetus. Most researchers believe that both genetic and environmental factors (such as diet) play a role. During the first 28 days of a pregnancy, the brain and spinal cord form in the developing fetus. The causes of human Spina bifida are not proven. The majority of babies with open spina bifida have a variety of medical problems including nerve damage and problems with motor function, this may include some amount of paralysis of the lower part of their body (this ranges from very mild to quite severe), loss of control of their bowels and bladder, and abnormalities of the brain. Closed spina bifida is probably more common than is currently recognised and includes a range of subtle abnormalities where the neural tube is closed. This is sometimes referred to as spina bifida occulta.

Historically, spina bifida was not detected before birth. Maternal serum screening of elevated alpha-fetoprotein at 16 to 18 weeks of gestation, followed by amniocentesis allowed detection of a minority of cases. A better option is the assessment of Acetyl choline Esterase form amniotic fluid. Today, detection rate is 98% at the time of an anatomical screen ultrasound at 20 weeks of gestation.

For decades the standard treatment has been to close the spinal defect soon after the baby is born. This is called postnatal surgery. It can also be treated through an experimental operation performed while the baby is still in the mother's womb, called prenatal surgery. The benefits of prenatal surgery remain unproven.

History

1980 - Fetal surgical techniques using animal models were first developed at the University of California, San Francisco by Dr. Michael R. Harrison, Dr. N. Scott Adzick and colleagues.

1994 - The surgical model that is most similar to simulating the human disease is the fetal lamb model of myelomeningocele (MMC) introduced by Meuli and Adzick in 1994. The MMC-like defect was surgically created at 75 days of gestation (term 145 to 150 days) by a lumbo-sacral laminectomy. Approximately 3 weeks after creation of the defect a reversed latissimus dorsi flap was used to cover the exposed neural placode and the animals were delivered by cesarean section just prior term. Human MMC-like lesions with similar neurological deficit were found in the control newborn lambs. In contrast, animals that underwent closure had near-normal neurological function and well-preserved cytoarchitecture of the covered spinal cord on histopathological examination. Despite mild paraparesis, they were able to stand, walk, perform demanding motor test and demonstrated no signs of incontinence. Furthermore, sensory function of the hind limbs was present clinically and confirmed electrophysiologically. Further studies.showed that this model when combined with a lumbar spinal cord myelotomy leads to the hindbrain herniation characteristic of the Chiari II malformation and that in utero surgery restores normal hindbrain anatomy. [2] [3] [4] [5]

Surgeons at Vanderbilt University, led by Dr. Joseph Bruner, attempted to close spina bifida in 4 human fetuses using a skin graft from the mother using specialized telescope called a laparoscope. Four cases were performed before stopping the procedure - two of the four fetuses died. [6]

1998 - Dr. N. Scott Adzick and team at The Children's Hospital of Philadelphia performed open fetal surgery for spina bifida in an early gestation fetus (22-week gestation fetus) with a successful outcome. [7]

Surgeons at Vanderbilt University, led by Dr. Noel Tulipan, made an incision in the mother's uterus to obtain better exposure to fetuses of 28 to 30 weeks gestation. All 4 fetuses were born premature but with evidence of reversal of their chiari II malformation. Only 2 of the 4 required ventricular shunts after birth. Fetal surgery after 25 weeks has not shown benefit in subsequent studies [8]

Subsequently, 4 medical centers conducted 253 open spina bifida repairs prior to the MOMs trial. The outcomes were mixed and the only comparison groups were other children that had not undergone repair after birth in the past. [9]

In February 2003, the National Institutes of Health began the Management of Myelomeningocele Study (MOMS). Three centers (Vanderbilt University, Children's Hospital of Philadelphia and the University of California at San Francisco) were chosen to participate in the study of 183 fetuses which were randomized, 91 for fetal repair and 92 for postnatal repair. The study took 8 years to complete at a cost of $22.5 million. [10] Of the 1,087 fetuses and mothers initially screened for the study, 183 met all the inclusion criteria. The Children's Hospital of Philadelphia treated 77 patients, University of California at San Francisco treated 54 and Vanderbilt University treated 52.

Medical information on the mothers and babies were gathered throughout the study and follow-up of their progress continued until the child reached at least two and a half years of age. Two outcomes were considered. The first, at 12 months, was death or need for a ventricular shunt. The second, measured at 30 months, was a composite score of standardized tests for mental and motor development.

Outcomes of the Trial

An interim analysis conducted in December 2010, made public in February 2011, and released in the New England Journal of Medicine in March 2011, showed a statistically significant benefit to the surgery and closed the trial. [1] The trial demonstrated that outcomes after prenatal spina bifida treatment are improved to the degree that the benefits of the surgery typically outweigh the maternal risks.

Based on these outcomes, fetal repair of spina bifida is now considered a standard of care at some fetal centers. However, prenatal repair is a complex and challenging procedure, requiring the most expert, comprehensive care for both mother and fetus. [11] The surgical team's level of experience in all aspects of care surrounding the operation are of paramount importance. Therapy that is highly dependent on the provider is of limited benefit to the wider population. [12]

See also

Related Research Articles

<span class="mw-page-title-main">Spina bifida</span> Birth defect of the spinal cord

Spina bifida /ˌspaɪnə ˈbɪfɪdə/ is a birth defect in which there is incomplete closing of the spine and the membranes around the spinal cord during early development in pregnancy. There are three main types: spina bifida occulta, meningocele and myelomeningocele. Meningocele and myelomeningocele may be grouped as spina bifida cystica. The most common location is the lower back, but in rare cases it may be in the middle back or neck.

<span class="mw-page-title-main">Iniencephaly</span> Rare neural tube defect characterised by fusion of the occiput with the spine

Iniencephaly is a rare type of cephalic disorder characterised by three common characteristics: a defect to the occipital bone, spina bifida of the cervical vertebrae and retroflexion of the head on the cervical spine. Stillbirth is the most common outcome, with a few rare examples of live birth, after which death invariably occurs within a short time.

<span class="mw-page-title-main">Prenatal testing</span> Testing for diseases or conditions in a fetus

Prenatal testing is a tool that can be used to detect some birth defects at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of the zygote, embryo, or fetus, either before gestation even starts or as early in gestation as practicable. Screening can detect problems such as neural tube defects, chromosome abnormalities, and gene mutations that would lead to genetic disorders and birth defects, such as spina bifida, cleft palate, Down syndrome, trisomy 18, Tay–Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X syndrome. Some tests are designed to discover problems which primarily affect the health of the mother, such as PAPP-A to detect pre-eclampsia or glucose tolerance tests to diagnose gestational diabetes. Screening can also detect anatomical defects such as hydrocephalus, anencephaly, heart defects, and amniotic band syndrome.

<span class="mw-page-title-main">Omphalocele</span> Rare abdominal wall defect in which internal organs remain outside of the abdomen in a sac

Omphalocele or omphalocoele also called exomphalos, is a rare abdominal wall defect. Beginning at the 6th week of development, rapid elongation of the gut and increased liver size reduces intra abdominal space, which pushes intestinal loops out of the abdominal cavity. Around 10th week, the intestine returns to the abdominal cavity and the process is completed by the 12th week. Persistence of intestine or the presence of other abdominal viscera in the umbilical cord results in an omphalocele.

A hysterotomy is an incision made in the uterus. This surgical incision is used in several medical procedures, including during termination of pregnancy in the second trimester and delivering the fetus during caesarean section. It is also used to gain access and perform surgery on a fetus during pregnancy to correct birth defects, and it is an option to achieve resuscitation if cardiac arrest occurs during pregnancy and it is necessary to remove the fetus from the uterus.

<span class="mw-page-title-main">Fetoscopy</span> Endoscopic procedure during pregnancy

Fetoscopy is an endoscopic procedure during pregnancy to allow surgical access to the fetus, the amniotic cavity, the umbilical cord, and the fetal side of the placenta. A small (3–4 mm) incision is made in the abdomen, and an endoscope is inserted through the abdominal wall and uterus into the amniotic cavity. Fetoscopy allows for medical interventions such as a biopsy or a laser occlusion of abnormal blood vessels or the treatment of spina bifida.

Prenatal development includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal development until birth.

<i>Hand of Hope</i> Photo of child in fetal surgery

Hand of Hope is a 1999 medical photograph taken by Michael Clancy during open fetal surgery, showing the hand of the fetus extending from the incision in the mother's uterus and seeming to grasp a surgeon's finger. Clancy was documenting a procedure being developed at Vanderbilt University to treat spina bifida. The photograph was taken on 19 August and the baby was safely delivered on 2 December.

<span class="mw-page-title-main">Neural tube defect</span> Group of birth defects of the brain or spinal cord

Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo begin to change shape and form the neural tube. When the neural tube does not close completely, an NTD develops.

<span class="mw-page-title-main">Fetal surgery</span> Growing branch of maternal-fetal medicine

Fetal surgery also known as antenatal surgery, prenatal surgery, is a growing branch of maternal-fetal medicine that covers any of a broad range of surgical techniques that are used to treat congenital abnormalities in fetuses who are still in the pregnant uterus. There are three main types: open fetal surgery, which involves completely opening the uterus to operate on the fetus; minimally invasive fetoscopic surgery, which uses small incisions and is guided by fetoscopy and sonography; and percutaneous fetal therapy, which involves placing a catheter under continuous ultrasound guidance.

<span class="mw-page-title-main">EXIT procedure</span>

The EXIT procedure, or ex utero intrapartum treatment procedure, is a specialized surgical delivery procedure used to deliver babies who have airway compression. Causes of airway compression in newborn babies result from a number of rare congenital disorders, including bronchopulmonary sequestration, congenital cystic adenomatoid malformation, mouth or neck tumor such as teratoma, and lung or pleural tumor such as pleuropulmonary blastoma. Airway compression discovered at birth is a medical emergency. In many cases, however, the airway compression is discovered during prenatal ultrasound exams, permitting time to plan a safe delivery using the EXIT procedure or other means.

<span class="mw-page-title-main">Ventriculomegaly</span> Increased size of the lateral ventricles

Ventriculomegaly is a brain condition that mainly occurs in the fetus when the lateral ventricles become dilated. The most common definition uses a width of the atrium of the lateral ventricle of greater than 10 mm. This occurs in around 1% of pregnancies. When this measurement is between 10 and 15 mm, the ventriculomegaly may be described as mild to moderate. When the measurement is greater than 15mm, the ventriculomegaly may be classified as more severe.

The Fetal Treatment Center at the University of California, San Francisco is a multidisciplinary care center dedicated to the diagnosis, treatment, and long-term follow-up of fetal birth defects. It combines the talents of specialists in pediatric surgery, genetics, obstetrics/perinatology, radiology, nursing, and neonatal medicine.

<span class="mw-page-title-main">Rachischisis</span> Neural tube defect in which the spinal cord is exposed

Rachischisis is a developmental birth defect involving the neural tube. This anomaly occurs in utero, when the posterior neuropore of the neural tube fails to close by the 27th intrauterine day. As a consequence the vertebrae overlying the open portion of the spinal cord do not fully form and remain unfused and open, leaving the spinal cord exposed. Patients with rachischisis have motor and sensory deficits, chronic infections, and disturbances in bladder function. This defect often occurs with anencephaly.

A fetus or foetus is the unborn offspring that develops from a mammal embryo. Following embryonic development, the fetal stage of development takes place. In human prenatal development, fetal development begins from the ninth week after fertilization and continues until the birth of a newborn. Prenatal development is a continuum, with no clear defining feature distinguishing an embryo from a fetus. However, a fetus is characterized by the presence of all the major body organs, though they will not yet be fully developed and functional and some not yet situated in their final anatomical location.

<span class="mw-page-title-main">Spinal disease</span> Diseases involving the vertebral column

Spinal disease refers to a condition impairing the backbone. These include various diseases of the back or spine ("dorso-"), such as kyphosis. Dorsalgia refers to back pain. Some other spinal diseases include spinal muscular atrophy, ankylosing spondylitis, lumbar spinal stenosis, spina bifida, spinal tumors, osteoporosis and cauda equina syndrome.

<span class="mw-page-title-main">Congenital pulmonary airway malformation</span> Medical condition

Congenital pulmonary airway malformation (CPAM), formerly known as congenital cystic adenomatoid malformation (CCAM), is a congenital disorder of the lung similar to bronchopulmonary sequestration. In CPAM, usually an entire lobe of lung is replaced by a non-working cystic piece of abnormal lung tissue. This abnormal tissue will never function as normal lung tissue. The underlying cause for CPAM is unknown. It occurs in approximately 1 in every 30,000 pregnancies.

<span class="mw-page-title-main">Memorial Hermann–Texas Medical Center</span> Hospital in Texas, United States

Memorial Hermann–Texas Medical Center is a nationally ranked hospital at the Texas Medical Center. It is the first hospital founded in the Texas Medical Center in Houston, Texas. Founded in 1925, it is the primary teaching hospital for McGovern Medical School and the flagship location of 13 hospitals in the Memorial Hermann Healthcare System. It is one of two certified Level I Trauma Centers in the greater Houston area. The Memorial Hermann Life Flight air ambulance service operates its fleet of helicopters from Memorial Hermann–Texas Medical Center. Pediatric care to the hospital is provided by Children's Memorial Hermann Hospital which treats infants, children, teens, and young adults age 0-21.

N. Scott Adzick currently serves as the Surgeon-in-Chief at Children’s Hospital of Philadelphia (CHOP) as well as the Director of CHOP’s Center for Fetal Diagnosis and Treatment, which he founded in 1995. Dr. Adzick is also the C. Everett Koop Professor of Pediatric Surgery at CHOP and a Professor of Pediatrics, Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania.

<span class="mw-page-title-main">Children's Memorial Hermann Hospital</span> Hospital in Texas, United States

Children's Memorial Hermann Hospital (CMHH) is a nationally ranked women's and pediatric acute care teaching hospital located in Houston, Texas. The hospital has 234 pediatric beds and 76 beds for women. CMHH is affiliated with the John P. and Kathrine G. McGovern Medical School at University of Texas Health Science Center at Houston and is a part of the Memorial Hermann Health System. The hospital provides comprehensive pediatric specialties and subspecialties to infants, children, teens, and young adults aged 0–21 throughout Houston and surrounding regions. Children's Memorial Hermann Hospital also sometimes treats adults that require pediatric care. CMHH also features an American College of Surgeons designated Level 1 Pediatric Trauma Center, 1 of 5 in the state. The hospital is located within the vast Texas Medical Center.

References

  1. 1 2 Adzick, N. Scott; Thom, Elizabeth A.; Spong, Catherine Y.; Brock, John W.; Burrows, Pamela K.; Johnson, Mark P.; Howell, Lori J.; Farrell, Jody A.; Dabrowiak, Mary E. (2011-03-17). "A randomized trial of prenatal versus postnatal repair of myelomeningocele". The New England Journal of Medicine. 364 (11): 993–1004. doi:10.1056/NEJMoa1014379. ISSN   1533-4406. PMC   3770179 . PMID   21306277.
  2. ↑ Meuli, M; Meuli-Simmen C; Hutchins GM; et al. "In utero repair of experimental myelomeningocele spares neurologic function at birth". J Pediatr Surg. 196 (31): 397–402.
  3. ↑ Bouchard, S; Davey MG; Rintoul NE; Walsh DS; Rorke LB; Adzick NS (2003). "Correction of hindbrain herniation and anatomy of the vermis following in utero repair of myelomeningocele in sheep". J Pediatr Surg. 38 (3): 451–58. doi:10.1053/jpsu.2003.50078. PMID   12632366.
  4. ↑ Pack, PW; Farmer DL; Wilkinson CC; et al. (2000). "Hindbrain herniation develops in surgically created myelomeningocele but is absent after repair in fetal lambs". Obstet Gynecol. 183 (5): 1119–23. doi:10.1067/mob.2000.108867. PMID   11084552.
  5. ↑ Meuli, M; Meuli-Simmen C; Hutchins GM; et al. (1995). "In utero surgery rescues neurologic function at birth in sheep with spina bifida". Nat Med. 1 (4): 342–47. doi:10.1038/nm0495-342. PMID   7585064. S2CID   29080408.
  6. ↑ Bruner, J; Tulipan N; Richards W. (1997). "Endoscopic coverage of fetal open myelomeningocele in utero". Am J Obstet Gynecol. 176 (1 Pt 1): 256–57. doi: 10.1016/s0002-9378(97)80050-6 . PMID   9024126.
  7. ↑ Adzick, N Scott; Sutton, Leslie N; Crombleholme, Timothy M; Flake, Alan W (21 November 1998). "Successful fetal surgery for spina bifida". The Lancet. 352 (9141): 1675–1676. doi: 10.1016/S0140-6736(98)00070-1 . PMID   9853442. S2CID   34483427.
  8. ↑ Tubbs, RS; Chambers, MR; Smyth, MD; Bartolucci, AA; Bruner, JP; Tulipan, N; Oakes, WJ (March 2003). "Late gestational intrauterine myelomeningocele repair does not improve lower extremity function". Pediatric Neurosurgery. 38 (3): 128–32. doi:10.1159/000068818. PMID   12601237. S2CID   24965555.
  9. ↑ "Fetal Surgery for Spina Bifida Video". Retrieved on 7 December 2011.
  10. ↑ Belluck, Pam. "Success of Spina Bifida Study Opens Fetal Surgery Door", "The New York Times", 9 February 2011. Retrieved on 7 December 2011.
  11. ↑ "Fetal Surgery for Spina Bifida". 2014-03-31.
  12. ↑ "Facts about Surgery for Myelomeningocele Repair". 2021-04-08.
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