General Topics
The papers below relate to survival, growth, development and parental experience. Click the title for the link.
Gil MM et al. Ultrasound Obstet Gynecol. 2015 Mar;45(3):249-66. doi: 10.1002/uog.14791. Epub 2015 Feb 1. Analysis of cell-free maternal DNA in maternal blood in screening for fetal aneuploidies: updated meta analysis
In this review article on cell-free DNA analysis of maternal blood (NIPT – Non Invasive Prenatal Testing), a range of results from various NIPT tests are presented.
It is important to keep in mind that NIPT is not a diagnostic test, that it is only a screening test. A positive result still has to be verified by invasive testing that carry a risk of miscarriage. The test is not recommended before the 11th week of pregnancy, as test results are not good enough at an earlier stage. They are recommended used in combination with fetal ultrasound, and depending on the screening procedures established in the country, only on women with positive maternal hormone screening results. NIPT will therefore not replace any of the diagnostics we use today, but be an addition to lower the number of invasive tests needed.
The results from this review indicate that NIPT reveal 91%-98.2% of fetal trisomies, while less than 0.09% - 0.!3% of the results falsely conclude that the fetus has a trisomy. When statistics are presented as close to zero, most of us automatically conclude that the test is nearly always correct. The numbers mislead us. (Think about this – one percent of my income (public physician) is far less than one percent of Bill Gates income.)
So when the tests wrongly conclude that a fetus has trisomy 13 in 0.13% of the cases (false positive rate), if we take my country, Norway, as an example, in 2013 there were 60464 registered pregnancies. 0.13% of this equals 79 pregnancies where the fetus does not have trisomy 13 even if the test indicates this (false positives). An estimated 12 pregnancies will be a fetus with trisomy 13, and a detection rate of 91% means that 11 of these will be discovered. The 12th will not, it is a false negative. So only one in seven pregnancies where the test indicates trisomy 13 will truly be a fetus with trisomy 13.
The accuracy of the test increases as the frequency of trisomy increases, so the numbers for Down syndrome will be a bit better. Trisomy 18 falls in between the two.
Of the 60464 Norwegian pregnancies, 120 were a fetus with Down syndrome. The NIPT would indicate Down syndrome in 119 of the 120 cases, but in 54 of the pregnancies, the test result falsely indicates that the fetus has Down syndrome (false positive), i.e. in 31% of the cases. The percentages of false positives for trisomy 18 will be 81% and for trisomy 13, 88%.
The accuracy of the NIPT depends on the woman´s age since the frequency of trisomy increases with maternal age. So for a pregnant woman age 20, the test will falsely state that a fetus has Down syndrome in 60% of the cases. In a 30-year old woman, this number has decreased to 45%, and in a 45 year old women to less than 5%. The test works best for high risk pregnancies.
The article concludes that cell-free DNA analysis can´t replace today´s screening tests, nor can it replace invasive diagnostics (amniocentesis or placental biopsy).
(This summary was written with the help of Jens Petter Gitlesen and his commentary: http://neitilsortering.no/2015/04/01/blodproven-som-tester-for-down-syndrom-er-svaert-upalitelig/)
Springett A L and Morris J K. 2014 J Med Screen 21: 113 Antenatal detection of Edwards (Trisomy 18) and Patau (Trisomy 13) syndrome: England and Wales 2005-2012
Nishi et al. 2014 Am J Med Genet A. 164:324-30 Surgical interventions for esophageal atresia in patients with trisomy 18
In this article, Nishi et al have reviewed 24 patients (9 boys, 15 girls) with full trisomy 18 and esophageal atresia (EA) at two Japanese clinics from 1982-2009. All children underwent intensive treatment including surgical interventions.
EA has earlier been reported as a cause for early death in babies with trisomy 18, but this study indicates that it is not a hopeless situation. Of the 24 patients, nine patients underwent gastrostomy (g-tube or peg which is a tube placed in stomach for feeding), but all passed away mainly due to cardiovascular conditions (heart conditions) before they could receive corrective EA surgery. 15 patients underwent corrective surgery for their EA. No children died during surgery. The one-year survival rate for these children was 27%. Two of the survivors were discharged home after 73 and 947 days in hospital.
The research group recommends a two-stage operation, first inserting a gastrostomy, then assessment and intensive management of the baby´s cardiopulmonary condition, before the corrective surgery.
Good information and discussion is crucial when counseling and considering the options.
Bruns, D. A. 2014. Clinical Nursing Studies, 2(1), 30-36. DOI: 10.5430/cns.v2n1p30. Caring for an infant with trisomy 18: A case study and guidelines
Bruns, D. A. and Campbell, E. 2014. American Journal of Medical Generics Part A, 164(3), 610-619. DOI: 10.1002/ajmg.a.36318 Twenty-two long-term survivors with full trisomy 18: Presenting and current medical conditions
Ancell, K. S. and Bruns, D. A. 2014. Journal of Genetic Disorders & Genetic Reports, 3(2). DOI: 10.4172/2327-5790.1000115 Maternal and paternal age at pregnancy for low incidence trisomy groups: Preliminary Findings and implications
Bruns, D. A. and Campbell, E. 2014. American Journal of Medical Genetics Part A. DOI: 10.1002/ajmg.a.36689 Nine children over the age of one year with full trisomy 13: A case series describing medical conditions
JUST RELEASED 164(12, 2987-2995
Guon J, Wilfond BS, Farlow B, Brazg T, Janvier A. 2013 Am J of Med Genet A. 164:308-318 Our children are not a diagnosis: The experience of parents who continue their pregnancy after a prenatal diagnosis of trisomy 13 or 18.
This article recounts the prenatal experience of 128 parents. Parents share their reasons to continue pregnancy, hopes, plan of treatment and the outcome of their child's life and birth.
Wu et al. 2013. Am J Med Genet Part A Survival of trisomy 18 (Edwards syndrome) and trisomy 13 (Patau Syndrome) in England and Wales: 2004-2011
This article features up to date information about survival of infants with trisomy 13 and 18. It is a population study with data that attempted to capture the outcome of every live born baby with trisomy 13 or 18 between 2004 and 2011. The authors conclude that 8% of babies born with trisomy 13 or 18 will survive beyond one year. They stress that even though the median survival time is only days, it does not mean that all children will die in weeks. The rate of death decreases significantly the older a child gets.
ITA believes that this is an informative study. Information on the medical care provided to or withheld from newborns is not included in the study but within the trisomy community it is generally known that children do not receive aggressive interventions in the UK. It is possible that a survival rate of 8% represents a minimum or natural survival rate.
Fitas et al. 2013. Case Rep Pediatr Mosaic trisomy 18 in a five-month-old infant.
This article reviews the difference between mosaic and full trisomy 18. It discusses chromosome tests using blood samples (peripheral leukocytes) and skin biopsies (skin fibroblasts) and concludes that when a child is diagnosed with mosaicism, there is no predictable relationship between the two test results.
Banka et al. 2013. World J Pediatr Trisomy 18 mosaicism: report of two cases.
This article describes two children who were found to have full trisomy or a high percentage of trisomy18 cells by blood sample (peripheral leukocytes) but had only a fraction of trisomy 18 cells by skin biopsy (skin fibroblast). When only some of the cells examined have an extra 18 chromosome, the child has mosaic trisomy 18. Both children in the article had minimal developmental delay even though they had many congenital anomalies.
ITA suggests that parents review this article, especially if treatment options by their physicians or medical system are withheld after a diagnosis of full trisomy but not for a diagnosis of mosaic trisomy. If the child is thriving or developing beyond what is typically expected for a baby with full trisomy, a skin biopsy might reveal that they are in fact, mosaic and not full. However, in theory, hundreds of cells from every organ in the body would need to be tested to reliably determine if a child has a full or mosaic trisomy condition.
Kosho et al. 2013. Am J Med Genet Part A Natural history and parental experience of children with trisomy 18 based on a questionnaire given to a Japanese trisomy 18 parental support group.
The article is based on parent-reported information for 65 children with full trisomy 18 in Japan. The article is important because it suggests factors associated with survival beyond the age of one year (full term birth, greater birth weight, absence of esophageal atresia and ability to breathe without ventilator support) The parents describe positively home life with surviving children and report that their children continue to learn including the ability to walk unassisted in two older children.
ITA notes that the Japanese parents’ description of a positive home life and happy children is very similar to that described in an earlier article (Janvier 2012) which summarizes the experience of 372 parents, mostly living in English-speaking countries.
Kumada et al. 2013. Am J Med Genet Part A Epilepsy in children with trisomy 18.
This article describes trisomy 18-related epilepsy for a group of 11 children over the age of twelve months, Sixty-four percent of the children were diagnosed with epilepsy and the article discusses corresponding treatment options and cautions.
Petrv et al. 2013. Am J Med Genet Part A Clinical features and prognosis of a sample of patients with trisomy 13 (Patau syndrome) from Brazil
Thirty children with trisomy 13 (73% with full trisomy 13) are described. Median survival was 30 days with no difference in survival noted between children with full or mosaic trisomy 13.
ITA notes that the nature of the care provided to newborns is not described. Three of the 30 children (all girls) are over the age of 8 but the absence/presence of holoprosencephaly (a common brain anomaly for trisomy 13) in these survivors is not indicated. The absence of this anomaly, especially in its more severe forms, has been associated with longevity– beyond one year.
Burke et al. 2013. Arch Dis Child Fetal Neonatal Ed Natural history of fetal trisomy 18 after prenatal diagnosis.
This article, from Ireland, describes the outcome of 23 children who were diagnosed prenatally with trisomy 18. (Termination of pregnancy is illegal in Ireland.) Only 39% of the children were born alive with all but one born before the 34th week of pregnancy. All newborns died within 48 hours. Details of the cause of death are provided. The authors conclude that while some children with trisomy 18 survive, those with a prenatal diagnosis have a bleaker prognosis.
ITA cautions that the findings of this article do not necessarily apply to all babies with a prenatal diagnosis. For no reason provided, most of the babies born were premature (born before 35 weeks gestation). Also, no information is provided related to the forms of treatment (resuscitation, oxygen, feedings etc ) if any, offered to newborns. If resuscitation were withheld in accordance to international guidelines, the chance of survival would decrease.
Nansi S. Boghossian et al. 2012. Am J Med Genet A. 0(2): 322–332. Anthropometric Charts for Infants with Trisomies 21, 18 or 13 Born between 22 Weeks Gestation and Term: The VON Charts
Data on birth weight for gestational age are not well described for infants with trisomy 21 (T21), trisomy 18 (T18), or trisomy 13 (T13). We report on anthropometric charts of infants with these conditions using data from the Vermont Oxford Network (VON). Data from a total of 5147 infants with T21 aged 22–41 weeks, 1053 infants with T18 aged 22–41 weeks and 613 infants with T13 aged 22–40 weeks were used to create birth weight for gestational age charts. Head circumference for gestational age charts were created for infants with T21 only. Combined-sex charts were generated for infants with T18 or T13 while sex-specific charts were generated for infants with T21. Smoothed centiles were created using LmsChartMaker Pro 2.3. Among the three examined groups, infants with T18 were the most likely to be growth restricted while infants with T21 were the least likely to be growth restricted. The new charts for infants with T21 were also compared to the Lubchenco and Fenton charts and both show frequent misclassification of infants with T21 as small or large for gestational age. The new charts should prove to be useful, especially for infants with T21, to assist in medical management and guide nutrition care decisions.
Peroos et al. 2012. BMJ Case Rep Longevity and Patau syndrome: what determines survival?
This article reviews the anomalies present in an 8 year old with full trisomy 13 and an additional eight reported cases of long term survivors (living beyond one year).
ITA notes that none of the surviving children described in this article had holoprosencephaly (a common type of brain anomaly in trisomy 13). It is possible that the absence of this anomaly is a factor contributing to increased longevity.
Janvier et al. 2012. Pediatrics The experience of families with children with trisomy 13 and 18 in social networks.
This article summarizes survey results of over 350 parents of children with trisomy 13 or 18. Parents overwhelmingly report a positive, enriching experience, regardless of their child’s life span. Almost all surviving children are described as happy although some parents admit that the effort and cost of caring for their children can be challenging.
Post about this article on the Neonatal Research Blog (Dr. Keith Barrington):
ITA notes that one of the co-authors of this paper, Barbara Farlow, is a cofounder of ITA.
Braddock et al. 2012. Augment Altern Commun. Communication ability in persons with trisomy 18 and trisomy 13.
The ability to communicate through hand gestures of 11 people with trisomy is described (eight with trisomy 18, three with trisomy 13.) The mean age of the participants in the sample is 16 years.
Bruns. 2012. Int J of Devel Disab Examining In-Home Care Needs and Work Responsibilities for Parents with Children with A Rare Trisomy Condition.
Based on the parent surveys submitted by parents to the Tracking Rare Incident Syndromes (TRIS) Study, the author reports on the experience of balancing work and home life with a child with trisomy 13 or 18 or similar condition.
ITA believes that this article provides necessary and important insight into the day to day challenges of raising a child with trisomy 13 or 18, including the need of in-home services. The author of this article, Dr. Debbie Bruns, is a cofounder of ITA.
Nelson et al. 2012. Pediatrics Inpatient hospital care of children with trisomy 13 and trisomy 18 in the United States.
The authors reviewed inpatient hospital care for 1997-2009 in the United States for admissions of children with trisomy 13 or 18. Most significantly, based on the large number of children admitted to hospital over the age of one, the authors conclude that, ‘universal application of the term “lethal” to a diagnosis of trisomy 13 and 18 is inappropriate.’
Tsukada et al. 2012. Cell Biochem Biophys Better prognosis in newborns with trisomy 13 who received intensive treatments: a retrospective study of 16 patients.
This article details the outcome of 16 children with trisomy 13 who were provided with Intensive medical interventions. Six of the 16 children survived beyond one year. Two long term survivors have a tracheostomy. None of the survivors in this group were diagnosed with alobar or semi-alobar holoprosencephaly. The authors conclude that children with trisomy 13 who survive beyond 60 days have a high probability of being long term survivors.
Bruns 2011. Am J Med Genet Part A Birth history, physical characteristics, and medical conditions in long-term survivors with full trisomy 13.
This article provides details of 30 long term survivors of full trisomy 13. This is the longest detailed report of such survivors.
ITA notes that the author of this paper, Dr. Debbie Bruns is a co-founder of ITA. Also, this paper is based on the research from the Tracking Rare Incidence Syndromes (TRIS) Study. See TRIS tab on ITA website for more information.
Courtwright et al. 2011. J Perinatol Length of life and treatment intensity in infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal.
The authors report lifespan and cost of care for infants with “lethal” conditions, including trisomy 13 and 18. The report includes 160 fetuses from North Carolina, USA hospitals between 1998-2003. All children born alive died before the age of four months. The authors conclude that babies with a prenatal diagnosis received less intensive care at less cost and lived less time than babies with a postnatal diagnosis.
Published response to this article by Dr. M Mccaffrey:McCaffrey. 2011. J Perinatol Lethality begets.
This article is a response to Courtwright et al 2011 (above). The author argues that the common belief that all children with trisomy 13 and 18 will die shortly after birth causes physicians to withhold or withdraw treatment and care as soon as a diagnosis is made often assuring the death of infants who might otherwise have survived. This phenomenon is known as the “self-fulfilling prophecy”.
http://www.ncbi.nlm.nih.gov/pubmed/21879002
Lakovschek et al. 2011. Am J Med Genet A Natural outcome of trisomy 13, trisomy 18, and triploidy after prenatal diagnosis.
This article details the outcome of 18 children (fifteen with trisomy 18, three with trisomy 13) whose mothers did not terminate their pregnancies following a prenatal diagnosis between 1999-2009 in Austria. Three children were born alive. All received comfort care with the maximum survival time of 87 hours.
ITA believes that there are difference interpretations of 'comfort care'. In some countries or hospitals, comfort care might mean providing the baby with care including food, oxygen and antibiotics, but not surgery or life support. In other countries or hospitals, comfort care might mean withholding fluids and nutrition and administer opiates such as morphine to keep the baby comfortable until death. ITA cautions parents on the need to discuss treatment options very carefully to ensure they understand the level of care that is being offered.
Bruns et al. 2011. J of Intellectual Disability Research ‘We’ve been through it all together’: Support for parents with children with rare trisomy conditions.
This article raises awareness of the need for family support of parents when raising a child with trisomy 13 and 18 and similar conditions. Twenty survey respondents experienced a range of positive and negative support from immediate and extended family members.
Thiele et al. 2011. Geburtshilfe Neonatol Clinical courses of trisomy 18 (Edwards syndrome) - an update (German article, English abstract)
This article is written in German with the abstract in English. The authors describe the birth of three children with trisomy 18 who lived (or are still living) an average of 20 months after receiving life-prolonging surgery. The authors conclude that on a case by case basis, surgery might be beneficial but they stress that the family needs to have a strong social network and secure socio-economic status to care for a child with trisomy 18.
Sibiude J et al. 2011. Fetal Diagn Ther Perinatal care and outcome of fetuses with trisomies 13 and 18 following a parental decision not to terminate the pregnancy.
This article, from France, recounts the outcome of 14 pregnancies diagnosed with trisomy 13 or 18 in which mothers refused termination. Four children were born alive and all died by the age of 11 days.
ITA cautions making conclusions about the risk of early death from this study because the gestational age and type of care provided to, (or withheld from), newborns were not provided.
Bruns 2010. Adv Neonatal Care Neonatal experiences of newborns with full trisomy 18.
This article describes the medical treatment provided to 21 newborns with full trisomy 18, of whom 13 were still living at the time of the study.
Jacob et al. 2010. Can J Neurol Sci. Long-term survival and late onset seizures in an adolescent with trisomy 13.
The authors report on a 15 year old with full trisomy 13. She is non-verbal and able to walk with a walker. She appears not to have holoprosencephaly and the authors comment that the absence of this anomaly is possibly related to long term survival.
Kumada et al. 2010. Pediatr Neurol. Epileptic apnea in a trisomy 18 infant.
The authors warn that some medications prescribed for babies with trisomy 18 diagnosed with central apnea (caffeine and theophylline for example) can be harmful to children who are diagnosed with epileptic apnea.
Vendola et al. 2010. Am J Med Genet Part A Survival of Texas infants born with trisomies 21, 18, and 13.
The authors reviewed the Texas birth registry and vital statistics for cases of trisomy 21, 18 and 13 between 1999 and 2003. They identified birth registrations for 398 children with trisomy 18 and 213 for trisomy 13. The one-year survival rate for both was 3%. The authors note that cardiac surgery is generally not offered to children with trisomy 18 or trisomy 13.
ITA notes that the shortcomings of a population study such as this one include the absence of information about gestational age and the type of care provided to or withheld from newborns.
Hsiao et al. 2009. Pediatr Neonatol Changing clinical presentations and survival pattern in trisomy 18.
This Japanese study reports on 31 consecutive cases of live born infants with full trisomy 18, 28 of whom with a postnatal diagnosis. Half were born by C-section suggesting that this proportion of babies may experience fetal distress during labor. Most of the children had a “do not resuscitate” order but of those who received interventions, 25% survived beyond one year. The authors state that severe polyhydramnios (excess amniotic fluid) in the mother was a factor related to early death.
Griffith 2009. Am J Med Genet A. Phenotypic variability in trisomy 13 mosaicism: Two new patients and literature review.
This paper is a review of the spectrum of children diagnosed with mosaic trisomy 13 including congenital anomalies and development ranging from minimal delays with a normal life span, to severe delays with a very shortened lifespan. It is not possible to predict a child’s future based the percentage of trisomy cells found in karyotyping (test to examine chromosomes in a sample of cells).
Wiedmeier et al. 2008. Am J Med Genet Part A Hematological abnormalities during the first week of life among neonates with trisomy 18 and trisomy 13: data from a multi-hospital healthcare system.
This article details various short-term blood imbalances that can occur in newborns with trisomy 13, and 18, some of which require medications or treatment.
ITA suggests that this article might be important to consider for birth plans that include some level of treatment.
Bruns 2008. Pregnancy and birth history of newborns with trisomy 18 or 13: a pilot study.
This article is an introduction to the Tracking Rare Incidence Syndromes (TRIS) Study.
Hsu et al. 2007. Am J Med Genet A Variable expressivity in Patau syndrome is not all related to trisomy 13 mosaicism.
This article, based on 13 live-born children with trisomy 13 in Taiwan, emphasizes the spectrum of the condition. One child with full trisomy 13 in the sample was 84 months old at the time of publication.
Tamame 2004. Am J Med Genet Part A Hyperinsulinemic hypoglycemia in a newborn infant with trisomy 13.
This article describes the association of hyperinsulinemic hypoglycemia (low blood sugar) in an infant with trisomy 13. The child was successfully treated with medication until the condition went away.
ITA notes that Wiedmeier et al (2008) provides more detail on short-term conditions among newborns, such as hypoglycemia. This article might be relevant to parents when creating birth plans.
Baty et al. 1994. Am J Med Genet Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk. Includes height and growth charts.
This paper, based on 98 parent surveys and their children’s medical records, describes the delivery, survival and related medical information about children with trisomy 13 and 18. This research provided the information from which trisomy 13 and 18 growth curves were developed. http://www.ncbi.nlm.nih.gov/pubmed/8116665 Magenis et al. 1968. J Pediatr Trisomy 13 (D1) syndrome: studies on parental age, sex ratio, and survival. This study, based on 172 children with trisomy 13, revealed a one-year survival rate of 13.5% and a median survival of two weeks to one month.
Baty, BJ, et al, 1994. Natural History of Trisomy 18 and Trisomy 13: II. Psychomotor Development
ITA believes that these two 1994 papers are remarkable because the reported and median survival rates from 1968, when the field of neonatology was in its infancy, were greater than they are today. Parents are often told that the one-year survival rate is 5-10% and the median age at death is approximately 5 days. The apparent reduction of survival rates over the past 45 years suggests that some newborns are not being supported when it is known before birth that they have a prenatal diagnosis, and that children with trisomy 13 are not realizing any benefit from advances in modern medicine.
This article features up to date information about survival of infants with trisomy 13 and 18. It is a population study with data that attempted to capture the outcome of every live born baby with trisomy 13 or 18 between 2004 and 2011. The authors conclude that 8% of babies born with trisomy 13 or 18 will survive beyond one year. They stress that even though the median survival time is only days, it does not mean that all children will die in weeks. The rate of death decreases significantly the older a child gets.
ITA believes that this is an informative study. Information on the medical care provided to or withheld from newborns is not included in the study but within the trisomy community it is generally known that children do not receive aggressive interventions in the UK. It is possible that a survival rate of 8% represents a minimum or natural survival rate.
Fitas et al. 2013. Case Rep Pediatr Mosaic trisomy 18 in a five-month-old infant.
This article reviews the difference between mosaic and full trisomy 18. It discusses chromosome tests using blood samples (peripheral leukocytes) and skin biopsies (skin fibroblasts) and concludes that when a child is diagnosed with mosaicism, there is no predictable relationship between the two test results.
Banka et al. 2013. World J Pediatr Trisomy 18 mosaicism: report of two cases.
This article describes two children who were found to have full trisomy or a high percentage of trisomy18 cells by blood sample (peripheral leukocytes) but had only a fraction of trisomy 18 cells by skin biopsy (skin fibroblast). When only some of the cells examined have an extra 18 chromosome, the child has mosaic trisomy 18. Both children in the article had minimal developmental delay even though they had many congenital anomalies.
ITA suggests that parents review this article, especially if treatment options by their physicians or medical system are withheld after a diagnosis of full trisomy but not for a diagnosis of mosaic trisomy. If the child is thriving or developing beyond what is typically expected for a baby with full trisomy, a skin biopsy might reveal that they are in fact, mosaic and not full. However, in theory, hundreds of cells from every organ in the body would need to be tested to reliably determine if a child has a full or mosaic trisomy condition.
Kosho et al. 2013. Am J Med Genet Part A Natural history and parental experience of children with trisomy 18 based on a questionnaire given to a Japanese trisomy 18 parental support group.
The article is based on parent-reported information for 65 children with full trisomy 18 in Japan. The article is important because it suggests factors associated with survival beyond the age of one year (full term birth, greater birth weight, absence of esophageal atresia and ability to breathe without ventilator support) The parents describe positively home life with surviving children and report that their children continue to learn including the ability to walk unassisted in two older children.
ITA notes that the Japanese parents’ description of a positive home life and happy children is very similar to that described in an earlier article (Janvier 2012) which summarizes the experience of 372 parents, mostly living in English-speaking countries.
Kumada et al. 2013. Am J Med Genet Part A Epilepsy in children with trisomy 18.
This article describes trisomy 18-related epilepsy for a group of 11 children over the age of twelve months, Sixty-four percent of the children were diagnosed with epilepsy and the article discusses corresponding treatment options and cautions.
Petrv et al. 2013. Am J Med Genet Part A Clinical features and prognosis of a sample of patients with trisomy 13 (Patau syndrome) from Brazil
Thirty children with trisomy 13 (73% with full trisomy 13) are described. Median survival was 30 days with no difference in survival noted between children with full or mosaic trisomy 13.
ITA notes that the nature of the care provided to newborns is not described. Three of the 30 children (all girls) are over the age of 8 but the absence/presence of holoprosencephaly (a common brain anomaly for trisomy 13) in these survivors is not indicated. The absence of this anomaly, especially in its more severe forms, has been associated with longevity– beyond one year.
Burke et al. 2013. Arch Dis Child Fetal Neonatal Ed Natural history of fetal trisomy 18 after prenatal diagnosis.
This article, from Ireland, describes the outcome of 23 children who were diagnosed prenatally with trisomy 18. (Termination of pregnancy is illegal in Ireland.) Only 39% of the children were born alive with all but one born before the 34th week of pregnancy. All newborns died within 48 hours. Details of the cause of death are provided. The authors conclude that while some children with trisomy 18 survive, those with a prenatal diagnosis have a bleaker prognosis.
ITA cautions that the findings of this article do not necessarily apply to all babies with a prenatal diagnosis. For no reason provided, most of the babies born were premature (born before 35 weeks gestation). Also, no information is provided related to the forms of treatment (resuscitation, oxygen, feedings etc ) if any, offered to newborns. If resuscitation were withheld in accordance to international guidelines, the chance of survival would decrease.
Nansi S. Boghossian et al. 2012. Am J Med Genet A. 0(2): 322–332. Anthropometric Charts for Infants with Trisomies 21, 18 or 13 Born between 22 Weeks Gestation and Term: The VON Charts
Data on birth weight for gestational age are not well described for infants with trisomy 21 (T21), trisomy 18 (T18), or trisomy 13 (T13). We report on anthropometric charts of infants with these conditions using data from the Vermont Oxford Network (VON). Data from a total of 5147 infants with T21 aged 22–41 weeks, 1053 infants with T18 aged 22–41 weeks and 613 infants with T13 aged 22–40 weeks were used to create birth weight for gestational age charts. Head circumference for gestational age charts were created for infants with T21 only. Combined-sex charts were generated for infants with T18 or T13 while sex-specific charts were generated for infants with T21. Smoothed centiles were created using LmsChartMaker Pro 2.3. Among the three examined groups, infants with T18 were the most likely to be growth restricted while infants with T21 were the least likely to be growth restricted. The new charts for infants with T21 were also compared to the Lubchenco and Fenton charts and both show frequent misclassification of infants with T21 as small or large for gestational age. The new charts should prove to be useful, especially for infants with T21, to assist in medical management and guide nutrition care decisions.
Peroos et al. 2012. BMJ Case Rep Longevity and Patau syndrome: what determines survival?
This article reviews the anomalies present in an 8 year old with full trisomy 13 and an additional eight reported cases of long term survivors (living beyond one year).
ITA notes that none of the surviving children described in this article had holoprosencephaly (a common type of brain anomaly in trisomy 13). It is possible that the absence of this anomaly is a factor contributing to increased longevity.
Janvier et al. 2012. Pediatrics The experience of families with children with trisomy 13 and 18 in social networks.
This article summarizes survey results of over 350 parents of children with trisomy 13 or 18. Parents overwhelmingly report a positive, enriching experience, regardless of their child’s life span. Almost all surviving children are described as happy although some parents admit that the effort and cost of caring for their children can be challenging.
Post about this article on the Neonatal Research Blog (Dr. Keith Barrington):
ITA notes that one of the co-authors of this paper, Barbara Farlow, is a cofounder of ITA.
Braddock et al. 2012. Augment Altern Commun. Communication ability in persons with trisomy 18 and trisomy 13.
The ability to communicate through hand gestures of 11 people with trisomy is described (eight with trisomy 18, three with trisomy 13.) The mean age of the participants in the sample is 16 years.
Bruns. 2012. Int J of Devel Disab Examining In-Home Care Needs and Work Responsibilities for Parents with Children with A Rare Trisomy Condition.
Based on the parent surveys submitted by parents to the Tracking Rare Incident Syndromes (TRIS) Study, the author reports on the experience of balancing work and home life with a child with trisomy 13 or 18 or similar condition.
ITA believes that this article provides necessary and important insight into the day to day challenges of raising a child with trisomy 13 or 18, including the need of in-home services. The author of this article, Dr. Debbie Bruns, is a cofounder of ITA.
Nelson et al. 2012. Pediatrics Inpatient hospital care of children with trisomy 13 and trisomy 18 in the United States.
The authors reviewed inpatient hospital care for 1997-2009 in the United States for admissions of children with trisomy 13 or 18. Most significantly, based on the large number of children admitted to hospital over the age of one, the authors conclude that, ‘universal application of the term “lethal” to a diagnosis of trisomy 13 and 18 is inappropriate.’
Tsukada et al. 2012. Cell Biochem Biophys Better prognosis in newborns with trisomy 13 who received intensive treatments: a retrospective study of 16 patients.
This article details the outcome of 16 children with trisomy 13 who were provided with Intensive medical interventions. Six of the 16 children survived beyond one year. Two long term survivors have a tracheostomy. None of the survivors in this group were diagnosed with alobar or semi-alobar holoprosencephaly. The authors conclude that children with trisomy 13 who survive beyond 60 days have a high probability of being long term survivors.
Bruns 2011. Am J Med Genet Part A Birth history, physical characteristics, and medical conditions in long-term survivors with full trisomy 13.
This article provides details of 30 long term survivors of full trisomy 13. This is the longest detailed report of such survivors.
ITA notes that the author of this paper, Dr. Debbie Bruns is a co-founder of ITA. Also, this paper is based on the research from the Tracking Rare Incidence Syndromes (TRIS) Study. See TRIS tab on ITA website for more information.
Courtwright et al. 2011. J Perinatol Length of life and treatment intensity in infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal.
The authors report lifespan and cost of care for infants with “lethal” conditions, including trisomy 13 and 18. The report includes 160 fetuses from North Carolina, USA hospitals between 1998-2003. All children born alive died before the age of four months. The authors conclude that babies with a prenatal diagnosis received less intensive care at less cost and lived less time than babies with a postnatal diagnosis.
Published response to this article by Dr. M Mccaffrey:McCaffrey. 2011. J Perinatol Lethality begets.
This article is a response to Courtwright et al 2011 (above). The author argues that the common belief that all children with trisomy 13 and 18 will die shortly after birth causes physicians to withhold or withdraw treatment and care as soon as a diagnosis is made often assuring the death of infants who might otherwise have survived. This phenomenon is known as the “self-fulfilling prophecy”.
http://www.ncbi.nlm.nih.gov/pubmed/21879002
Lakovschek et al. 2011. Am J Med Genet A Natural outcome of trisomy 13, trisomy 18, and triploidy after prenatal diagnosis.
This article details the outcome of 18 children (fifteen with trisomy 18, three with trisomy 13) whose mothers did not terminate their pregnancies following a prenatal diagnosis between 1999-2009 in Austria. Three children were born alive. All received comfort care with the maximum survival time of 87 hours.
ITA believes that there are difference interpretations of 'comfort care'. In some countries or hospitals, comfort care might mean providing the baby with care including food, oxygen and antibiotics, but not surgery or life support. In other countries or hospitals, comfort care might mean withholding fluids and nutrition and administer opiates such as morphine to keep the baby comfortable until death. ITA cautions parents on the need to discuss treatment options very carefully to ensure they understand the level of care that is being offered.
Bruns et al. 2011. J of Intellectual Disability Research ‘We’ve been through it all together’: Support for parents with children with rare trisomy conditions.
This article raises awareness of the need for family support of parents when raising a child with trisomy 13 and 18 and similar conditions. Twenty survey respondents experienced a range of positive and negative support from immediate and extended family members.
Thiele et al. 2011. Geburtshilfe Neonatol Clinical courses of trisomy 18 (Edwards syndrome) - an update (German article, English abstract)
This article is written in German with the abstract in English. The authors describe the birth of three children with trisomy 18 who lived (or are still living) an average of 20 months after receiving life-prolonging surgery. The authors conclude that on a case by case basis, surgery might be beneficial but they stress that the family needs to have a strong social network and secure socio-economic status to care for a child with trisomy 18.
Sibiude J et al. 2011. Fetal Diagn Ther Perinatal care and outcome of fetuses with trisomies 13 and 18 following a parental decision not to terminate the pregnancy.
This article, from France, recounts the outcome of 14 pregnancies diagnosed with trisomy 13 or 18 in which mothers refused termination. Four children were born alive and all died by the age of 11 days.
ITA cautions making conclusions about the risk of early death from this study because the gestational age and type of care provided to, (or withheld from), newborns were not provided.
Bruns 2010. Adv Neonatal Care Neonatal experiences of newborns with full trisomy 18.
This article describes the medical treatment provided to 21 newborns with full trisomy 18, of whom 13 were still living at the time of the study.
Jacob et al. 2010. Can J Neurol Sci. Long-term survival and late onset seizures in an adolescent with trisomy 13.
The authors report on a 15 year old with full trisomy 13. She is non-verbal and able to walk with a walker. She appears not to have holoprosencephaly and the authors comment that the absence of this anomaly is possibly related to long term survival.
Kumada et al. 2010. Pediatr Neurol. Epileptic apnea in a trisomy 18 infant.
The authors warn that some medications prescribed for babies with trisomy 18 diagnosed with central apnea (caffeine and theophylline for example) can be harmful to children who are diagnosed with epileptic apnea.
Vendola et al. 2010. Am J Med Genet Part A Survival of Texas infants born with trisomies 21, 18, and 13.
The authors reviewed the Texas birth registry and vital statistics for cases of trisomy 21, 18 and 13 between 1999 and 2003. They identified birth registrations for 398 children with trisomy 18 and 213 for trisomy 13. The one-year survival rate for both was 3%. The authors note that cardiac surgery is generally not offered to children with trisomy 18 or trisomy 13.
ITA notes that the shortcomings of a population study such as this one include the absence of information about gestational age and the type of care provided to or withheld from newborns.
Hsiao et al. 2009. Pediatr Neonatol Changing clinical presentations and survival pattern in trisomy 18.
This Japanese study reports on 31 consecutive cases of live born infants with full trisomy 18, 28 of whom with a postnatal diagnosis. Half were born by C-section suggesting that this proportion of babies may experience fetal distress during labor. Most of the children had a “do not resuscitate” order but of those who received interventions, 25% survived beyond one year. The authors state that severe polyhydramnios (excess amniotic fluid) in the mother was a factor related to early death.
Griffith 2009. Am J Med Genet A. Phenotypic variability in trisomy 13 mosaicism: Two new patients and literature review.
This paper is a review of the spectrum of children diagnosed with mosaic trisomy 13 including congenital anomalies and development ranging from minimal delays with a normal life span, to severe delays with a very shortened lifespan. It is not possible to predict a child’s future based the percentage of trisomy cells found in karyotyping (test to examine chromosomes in a sample of cells).
Wiedmeier et al. 2008. Am J Med Genet Part A Hematological abnormalities during the first week of life among neonates with trisomy 18 and trisomy 13: data from a multi-hospital healthcare system.
This article details various short-term blood imbalances that can occur in newborns with trisomy 13, and 18, some of which require medications or treatment.
ITA suggests that this article might be important to consider for birth plans that include some level of treatment.
Bruns 2008. Pregnancy and birth history of newborns with trisomy 18 or 13: a pilot study.
This article is an introduction to the Tracking Rare Incidence Syndromes (TRIS) Study.
Hsu et al. 2007. Am J Med Genet A Variable expressivity in Patau syndrome is not all related to trisomy 13 mosaicism.
This article, based on 13 live-born children with trisomy 13 in Taiwan, emphasizes the spectrum of the condition. One child with full trisomy 13 in the sample was 84 months old at the time of publication.
Tamame 2004. Am J Med Genet Part A Hyperinsulinemic hypoglycemia in a newborn infant with trisomy 13.
This article describes the association of hyperinsulinemic hypoglycemia (low blood sugar) in an infant with trisomy 13. The child was successfully treated with medication until the condition went away.
ITA notes that Wiedmeier et al (2008) provides more detail on short-term conditions among newborns, such as hypoglycemia. This article might be relevant to parents when creating birth plans.
Baty et al. 1994. Am J Med Genet Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk. Includes height and growth charts.
This paper, based on 98 parent surveys and their children’s medical records, describes the delivery, survival and related medical information about children with trisomy 13 and 18. This research provided the information from which trisomy 13 and 18 growth curves were developed. http://www.ncbi.nlm.nih.gov/pubmed/8116665 Magenis et al. 1968. J Pediatr Trisomy 13 (D1) syndrome: studies on parental age, sex ratio, and survival. This study, based on 172 children with trisomy 13, revealed a one-year survival rate of 13.5% and a median survival of two weeks to one month.
Baty, BJ, et al, 1994. Natural History of Trisomy 18 and Trisomy 13: II. Psychomotor Development
ITA believes that these two 1994 papers are remarkable because the reported and median survival rates from 1968, when the field of neonatology was in its infancy, were greater than they are today. Parents are often told that the one-year survival rate is 5-10% and the median age at death is approximately 5 days. The apparent reduction of survival rates over the past 45 years suggests that some newborns are not being supported when it is known before birth that they have a prenatal diagnosis, and that children with trisomy 13 are not realizing any benefit from advances in modern medicine.
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