|
 
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| REVIEW ARTICLE |
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| Year : 2015 | Volume
: 4
| Issue : 2 | Page : 75-81 |
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Preterm babies at a glance
Maria Serenella Pignotti, Gianpaolo Donzelli
Department of Fetal-Neonatal, Anna Meyer Children Hospital, University of Florence, Firenze, Italy
| Date of Web Publication | 6-Apr-2015 |
Correspondence Address:
Dr. Maria Serenella Pignotti
Department of Fetal-Neonatal, Anna Meyer Children Hospital, University of Florence, Viale Pieraccini 24, 50142 Firenze
Italy
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2249-4847.154546
Preterm births, defined as a birth before 37.0 weeks gestation, are a main worldwide health problem. In the world, every year, about 15 million babies are born preterm, and their incidence is rising. Broadly outcomes improve with increasing gestational age; however, health care needs for preterm survivors can be extensive, both in terms of immediate postnatal support for infants and their families and in terms of lifelong support. The effect on the lifespan for the survivors especially in terms of mental health and cardiometabolic status need more attention and researches. A deeper awareness by pediatricians to the impact of preterm birth on the developing of adult diseases and pathological conditions could be of help in preserving and maintaining health once the child become an adult and in optimizing his/her impact on society. Keywords: Guidelines, neonate, outcome, prematurity, survival
How to cite this article:
Pignotti MS, Donzelli G. Preterm babies at a glance. J Clin Neonatol 2015;4:75-81 |
| Introduction | |  |
Preterm birth is a worldwide serious problem. In the past 50 years there was an amazing change in the care of neonates: A 1000-g birth weight infant born in 1960 had a mortality risk of 95% against a 95% probability of survival by 2000. First physicians to be interested in the newborn were obstetricians, and only in the second half of the 19 th century the preterm babies were sought as viable. In the middle of the 20 th century, pediatricians took the responsibility for neonates and only in 1960 the term "neonatology" was coined, probably by Alexander Shaffer. In those years, a conceptual revolution was the comprehension of the clinical difference between birth weight and gestational age, and this distinction became habitual. Neonatal intensive care started in 1960s in most industrialized countries. The next decade was a transitional period when Neonatal Intensive Care Units (NICUs) were being established. In 1980 survival of the most immature infants improved and approached 50%. In 1990 surfactant and in 1995 antenatal steroids changed the fate of thousands of preterm babies. The impact of exogenous surfactant on neonatal survival was enormous. At the beginning of this century, technological and pharmacologic advances led to offer active treatment to the 22, 23, 24 weekers. In point of fact, in the world, every year, an estimated 15 million babies are born preterm, about 41,000 each day and around 5% of these at an extremely preterm age. [1],[2] The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries. [3] However, the rate of preterm birth is rising. The causes are predominantly linked to iatrogenic preterm deliveries, artificially conceived multiple pregnancies and advanced maternal age. [3],[4] This increase approaches 31% since 1981, in USA. Actually, preterm birth is a major global public health issue due to its prevalence, impact upon mortality and morbidity and cost implications. Prematurity is the leading cause of neonatal mortality, and it is accountable for nearly one-half of long-term neurological sequelae. Preterm birth complications are the foremost cause of death among children under 5 years of age, responsible for nearly 1 million deaths each year. Many survivors face a lifetime of disability, including learning and visual and hearing problems. [1] The risk of adverse consequences declines with increasing gestational age but infants born at 38 and 39 weeks of gestation (weeks-GA) are also of a higher-risk than those for infants born at 40 weeks-GA for poor outcome, with neonatal mortality risk increasing again in infants born beyond the 42° weeks-GA. [5]
| Defining the Topic | | |
Preterm birth is a syndrome with a variety of causes which can be roughly classified into two groups: A - spontaneous preterm birth and b - iatrogenic preterm birth (when the risk of continuing the pregnancy, to either the mother or the baby, is perceived as greater than the risks of preterm birth). The increase in iatrogenic preterm delivery is associated with a reduction in neonatal mortality. [6] Two-thirds of preterm birth follow spontaneous onset of labor. Preterm birth can be due to "maternal" causes, related to a preexisting maternal medical disorder, such as diabetes, to "obstetrical" or "pregnancy-related" causes, including hypertensive disorders, hemorrhage, and finally, "fetal" causes. Spontaneous preterm birth is regarded as a syndrome resulting from multiple causes, infection, inflammation and vascular disease causing the uterus to change from quiescence to active contractions. The precise cause of spontaneous preterm labor remains unidentified in up to half of all cases. Many maternal factors have been associated with an increased risk of spontaneous preterm birth, including young or advanced maternal age, under 20 and over 40 years, short interpregnancy intervals, black race, periodontal disease, low maternal body mass index, multiple pregnancy, preexisting noncommunicable disease, hypertensive disease of pregnancy, infections. [3],[7],[8],[9] Fetuses with congenital malformations are also at a higher-risk of preterm birth. A family history of preterm deliveries is a very strong risk factor [10] but the strongest risk factor is a prior preterm birth: A woman with a history of spontaneous preterm birth has a 2.5-fold increased risk of preterm delivery in her next pregnancy. [11] Epidemiologic studies suggest that there is a genetic susceptibility to preterm birth. The heritability of preterm birth is estimated to be around 25-40%. [12] It was suggested that the influences of genetic background on a common, complex condition such as preterm birth occur in the context of an environmental milieu, and it is presumably this convergence that produces the phenotype of preterm birth. [13]
| Defining the Cohort | | |
According to the definition, by WHO, a preterm neonate is a baby born alive before 37 completed weeks of pregnancy. [1] Preterm birth is sub-classified into extremely preterm (<28.0 weeks gestation), very preterm (28 to <32.0 weeks gestation), moderate preterm (32 to <34.0 weeks gestation), late preterm (34 to <37.0 weeks gestation). [14],[15] On recent data extremely preterm accounts for 5%, very preterm for about 15%, moderate for 20% and late preterm for 60-70% of the total number. [3] Inequalities in survival rates around the world are stark. In low-income settings, half of the babies born at 32 weeks (2 months early) die due to a lack of feasible, cost-effective care, such as warmth, breastfeeding, basic care for infections and breathing difficulties. In high-income countries, almost all of these babies survive. More than three-quarters of these babies can be saved with feasible, cost-effective care, such as essential care during child birth and neonatal age for every mother and baby, steroid treatment to the mother, kangaroo mother care and antibiotics for infections. Moderately-premature babies without complications can be cared for with their mothers on normal postnatal wards or even at home, but babies under 32.0 weeks-GA are at greater risk of developing complications and will usually require hospital admission. Fewer babies are born under 28.0 weeks-GA, and most of these will require intensive care. Particularly babies born before 26.0 weeks-GA are at the main risk for mortality, morbidity and serious cognitive, neuro-motor and sensory damage. Globally, they are at greater risk for poorer health outcomes. These babies represent the cutting edge of neonatal medicine throughout the developed world and the appropriateness or not of offering them active intensive care is a matter of great debate and polarized views. Preterm newborns delivered at <25 completed weeks-GA are often labeled as infants of uncertain viability [16],[17],[18],[19],[20] or periviable babies. [21] Although the prevalence of such births is <1% they account for nearly one-half of all cases of perinatal mortality. [17] Actually, the 25-weekers and below pay the biggest price to mortality and morbidity. These babies-once delivered alive, are likely to need at least 4-5 months or longer of inpatient care, many required long-term care and are at high-risk of death or disability for a lifelong time.
| About Survival | | |
As reported, preterm birth is the most common cause of neonatal death, worldwide, even if there are radically different patterns in survival rates across the world. In industrialized countries, about 50% of preterm infants born at 24 weeks-GA survive to discharge from hospital and up to 90% at 28 weeks-GA. On the contrary, in low-income countries <10% of 28-weekers survive while 34 and more weekers show a 50% possibility of survival. [22] Survival is gestational age-specific and improves quickly day after day of gestation. At present, in more industrialized countries, the most part of preterm over 28 weeks survive to discharge, but they are at a higher-risk of death and morbidity for the lifespan. When evaluating neonatal survival and outcome data, it is important to eliminate selection bias as much as possible as the data can be confounding, for example, with different population of referral. [23],[24] Survival is gestational age-specific. [22] EPICure Study 2 studied the short-term outcome of the most tiniest preterm babies, born at 22-26 weeks-GA and showed an increased survival since 1995 [25],[26] for 24-25 weekers but not for babies born a 22-23 weeks-GA. [27],[28] Improvement in survival seem to be a result of better care in the 1 st week of life and better transportation to NICUs, as well as the use of surfactant and antenatal corticosteroids. The pattern of major neonatal morbidity remained, instead, substantially unchanged. [27] This carries important social implications whit an increase in the number of survivors at risk of serious later health problems. EPICure Study 2 showed also that the number of admissions to NICUs of periviable infants increased by 44% in the last decade that means an increasing of allocation of resources.
| About Outcome and Sequelae | | |
Preterm birth is a pervasive disorder that impacts all the functioning of the child with a high-risk of pathological conditions on short- and long-term basis. Most of these sequelae have the potential to impact the neurodevelopment, education, behavior, psychosocial, growth and health outcome. Morbidity is inversely related to gestational age even if there is no gestational age that is completely excepted. Outcome largely depends on the place and facilities for the care at birth and in the neonatal age with stark differences among countries. Many of these children, during preschool years, show attention, regulatory problems and Attention Deficit Hyperactivity Disorder (ADHD), and in childhood, inattention, peer relationship problems and emotional difficulties. Approximately 25% have psychiatric disorders, and up to 50% have significant problems that impact the functioning. [29] A markedly increased prevalence of autism spectrum disorders (ASD) in the preterm population is also reported. Studies show continuity in outcomes across the lifespan. The attention, emotional or peer relationship problems may not meet diagnostic criteria, but they may impact on daily function severely. These behaviors show continuity in adulthood. Based on behavioral and neuroimaging studies, the causative pathway may be identified in aberrant brain development on a neurodevelopmental origin: The so-called "Encephalopathy of Prematurity" characterized by focal brain injury and altered brain development. Periventricular Leukomalacia is a cerebral white matter injury characterized by focal necrotic lesions with subsequent cists transformation. It is a common and serious problem in the preterm population. However, even in absence of brain injury, altered brain maturation and vulnerability due to premature entrance to the extrauterine life can be associated with brain structural and microstructural changes such as neuronal-axonal disturbance that could underlie the most common neurologic sequelae: Abnormalities of cognition, attention, behavior, speech, that could occurs together or not to the white matter injury. [30],[31] About pathogenesis, the birth in a period of rapid brain growth, is thought to disrupt the genetically programmed pattern of brain genesis, that, jointly with early exposure to other insults -NICU-environment, unnatural movement due to gravity, altered sensorial stimulation by light and sound, postnatal insufficient growth, smaller muscle size, altered parent-child interaction, can be the causes of the preterm neurodevelopmental sequelae. [32] The neonatal central nervous system immaturity and its subsequent vulnerability to injuries plays an important role that carries special risks for brain damage resulting in clinical disorder, which often persist into adult life. Johnson and Marlow identified a "preterm behavioral phenotype" characterized by an increased risk for symptoms and disorders associated with inattention, anxiety, and social difficulties. [33],[34] The most common long-term neurodevelopmental disability associated with preterm birth is cerebral palsy, but less than half of global cases of cerebral palsy are related to preterm birth. The prevalence of cerebral palsy varies by gestational age, with the risk increasing at lower gestational ages. Mild and moderate motor impairments, consistent with developmental coordination disorder, occur in almost half of those children born preterm and include delay in crawling and walking, difficulties with balance, manual dexterity, and ball skills. [32] Epilepsy, associated to cerebral palsy or not, is also more common among ex-preterm children, with a prevalence of about 31%. [24] Cognitive impairment is also common. [35] Approximately one-third of all preterm infants have some cognitive impairment; 7% are severely impaired. [36] A further 14% have mild cognitive impairment [36] such as subtle differences in IQ scores, performance in reading, writing, and mathematics, and poorer examination performance when compared with full-term infants. [37] Preterm infants commonly show delays in acquisition of expressive language, receptive language processing, and articulation and deficits in phonological short-term memory. Impairment remains evident in school age and adolescence. [38] Often they show, later in life, special educational needs. [37] Teachers and parents report a range of behavioral problems and evidence suggests ex-preterm children to be at greater risk of ADHD than term-born peers, although estimates of the magnitude of the risk vary. Preterm infants suffer a six-fold risk of developmental co-ordination disorder, including disorders of attention and activity compared with term-born children with a major prevalence in lower gestational age. Higher is also the prevalence of behavior disorders. [24] Besides, immediately after discharge but even in their early years, preterm born infants are more likely to be readmitted to hospital, due to problems related to prematurity or to respiratory illness. Even in peripuberal age ex-extremely preterm children have greater needs for services as physician visits, occupational or physical therapy, nursing or medical procedures. [36] Hospital readmissions appear to decrease to a similar rate by young adulthood. [39] Up to 40% of preterm, survivors suffer from bronchopulmonary dysplasia that remains a severe complication of prematurity in spite of prenatal steroids and surfactant treatment. Its incidence is differently distributed in gestational age: From 67% of the extremely preterm, to 37% among the very preterm. [40],[41] Necrotizing enterocolitis is almost exclusively seen in preterm infants with an incidence between 4% and 7%, roughly one-third of children needing surgery, a mortality rate between 12% and 30% and surviving infants at higher-risk of long-term problems. The ORACLE Children Study demonstrated significant long-term consequences of gut function (presence of stoma, admission for bowel problems and continuing medical care for gut-related problems) and motor, sensory and cognitive outcome in children which suffered from necrotizing enterocolitis. [42] Up to 3% of very preterm infants suffer from retinopathy of prematurity with severe visual impairment in up to 8% of tiniest infants. Other frequent problems are myopia and hypermetropia, which may require glasses early in life. [24] Another adverse outcome is a high rate of late retinal detachment in extremely preterm infants during their late teens. [36] Hearing impairment is stable at around <3-5% in low gestational age, nevertheless, these children are about 25 times more likely to be hearing impaired than the general population. It is important to remember the strong cumulative detrimental effect of hearing impairment on the acquisition of language skills and learning. [36] Moreover, the smallest preterm are shorter and lighter when compared with term peers at term corrected-age. Growing up, the weight disadvantages diminished but the height difference persists over time. [39] Reassuringly, perception of quality of life in young adulthood is generally similar to term-born peers. [39],[43]
| The Ex-Preterm Adolescent and Adult | | |
Many outcomes in premature children remain sub-clinical before adolescence. Adolescence is a key period for mental health. Recently many studies pointed the attention to the ex-preterm adolescence as neuropsychological and behavioral deficits, social and emotional problems can account for a substantial proportion of the longer-term impairment in these children. Around 25% of ex-preterm adolescents show psychiatric disorders. [34] Neurodevelopmental problems, inattention, anxiety, socio-communicative problems, ADHD, emotional problems, and autism are prevalent in ex-preterm adolescents when compared to term born normal birth weight children. Executive functions (information processing, attention control, cognitive flexibility, goal setting) seems to be deficient among these teenagers and could lead to poorer academic achievement and social-emotional competence which may lead to difficulty in transitioning to adult independence. About adulthood, the survivors of the initial years of modern perinatal care are now in their thirties and forties. The majority of preterm survivors does well and live fairly normal lives. However, even if these children, by the time they reach adulthood, do better than expected in term of adult functioning and live rather normal lives, many of them may show chronic health conditions and functional limitations. Special challenges the aging premature infant may face across the lifespan, most of them probably unknown. This is especially true in the lowest gestational age. There are suggestions of higher rates of psychopathology and other health problems such as diabetes, hypertension, insulin resistance, atherosclerosis and cardiovascular disease as these individuals reach middle age. Educational disadvantage associated with lower birth weight persists into early adulthood. [44] Concerns about adult role functioning, life achievements, social functioning, self-perceived quality of life for this new population are of great interest even for its possible public health implications. The undoubted knowledge that the most part of these ex-preterm adults are doing well doesn't eliminate concerns about their life course, especially regarding psychopathology, cardiovascular and metabolic problems. [45] Ex-preterm adults seems to have more cardiometabolic risk factors, particularly those ex-very small or very preterm: High blood pressure, lower lean body mass, altered glucose regulation and probably, a more atherogenic lipid profile. Low rate of physical activity and a less healthy diet are also reported. [45] Adult born extremely preterm seems less likely to leave the parental home and to start cohabiting with an intimate partner and were also less likely to experience sexual intercourse, than it is not surprising that fertility rates are relatively lower in survivors of extreme prematurity. [46] The two major predictors of adult outcomes are lower gestational age that reflects perinatal injury and family sociodemographic status, which reflects both genetic and environmental effects. [47] About mental health, recently some authors highlighted the strong link between certain perinatal conditions and some adult psychiatric disorder. Nosarti et al. [48] shown an association between preterm birth and both depressive disorder and bipolar affective disorder with more than double the risk of nonaffective psychosis for the ex-32 weekers and below, an almost tripled risk of depressive disorder and >7 times greater risk of bipolar affective disorder. Halmøy et al. shown [29] preterm birth associated with 1.3 and five-fold increases in the risk of ADHD, respectively, for the <37 weekers and <28 weekers, persisting up to 40 years after birth. Other psychiatric disorders are of interest for the neonatologist such as the ASD. Existing reports are focused on cohorts of children born a lot of years ago, before surfactant and antenatal corticosteroids era and as the most vulnerable surviving babies (below 28 weeks gestation) are born after 1990 and they are now reaching adulthood, some authors suggested a mental health surveillance, [49] that would be beneficial for the individual and for society. While the knowledge of higher levels of cardiometabolic risk factors can be reduced by a healthy lifestyle and appropriate early diagnosis and treatment that can be advantageous for individuals and have favorable public health implications.
| Societal and Familiar Consequences | | |
The impact on modern societies of the very long-term consequences of preterm birth is possibly great. A very special aspect of preterm birth is related to parents and family outcome, which deserve special attention. Prematurity and its sequelae have an enormous negative psychosocial and emotional effect on the family. After the first more distressing months of life, by the age of 3, even for healthy children, parenting stress remained greater than for term infants. The severity of parental stress is related with low family income, less education, major severity of child's handicap. [36] Parents and the whole family environment have a pronounced influence on child development and have the potential to provide a buffer against poor outcomes for children at high-risk. More preterm is the baby; heavier is the burden of care on parental emotional status. However, the relationships are also reciprocal. Thus, understanding parental mental health outcome following these stressful births is particularly important due to potential negative effects on child's health while the opposite is true, as well. These parents, both mothers and fathers, report higher level of mental health problems, increased parenting stress and an increased negative impact on family systems that appear to diminish over time but they need early, specific and targeted support for themselves and their child. [50] Fathers show higher rates of psychological distress immediately after birth, but slightly lower than for mothers. Fathers play an important role in supporting mothers and promoting child development through an increasing in family cohesion, reducing maternal distress, providing a buffer for infants if the mother is experiencing clinically significant mental health problems. [51] The baby's specific characteristics (medical illnesses, disabilities.) seems to be the stronger predictor of family outcome even if other factors such as parental environment (socioeconomic status, parental education, marital satisfaction, social support…) play an important role. On societal perspective, the medical costs per child vary according to gestational age and are highest in the 1 st year of life but remain high in subsequent years, and they are higher for the lowest gestational age.
| The Ethical Dilemma | | |
Thanks to technological progress the outcome for high-risk neonates has improved, and the limit of human viability is shifted toward a younger and younger gestational age and birth weight. However, with the more positive result, modern perinatal care has also brought to light concerns on the ethical basis of neonatal intensive care. Concerns arise from the high prevalence of developmental disabilities, the long staying in the hospital, the burden of suffering and separation from the family, the high level of technology these babies need. The burdens for babies, family and society are controversial. In the field of extreme prematurity, there is a passionate debate about the options of care. Guidelines for treatment for mother and babies at the threshold of viability were developed in several countries, [52],[53] followed by more recent statements. [54],[55] However, neonatologists and parents' attitude is strongly influenced by the religious, social and cultural background of their country and were guidelines are missing, scholars often ask for them. [56] Anyway, basically, the approach of the pediatric world doesn't seem so controversial, with a call for a more individualized approach in the lowest weeks-GA, with both the options, full intensive and palliative care, deserving dignity and attention by the clinicians. There is, as well, a strong respect for parental authority even if not considered unlimited and emphasis is put on the counseling process.
| Conclusion | | |
Although preterm birth rate has not declined, advances in perinatal care have dramatically increased their survival rate even in extreme gestational ages and a significant majority of preterm survivors are leading productive lives, as they approach middle age. Interventions to improve the outcome of preterm neonates can be primary (directed to all women), secondary (aimed at eliminating or reducing risks), or tertiary (planned to improve outcomes for babies). [57] In last decades, most successful efforts were tertiary interventions-regionalized care, surfactants, antibiotics, care in the NICUs, advances in neonatal resuscitation techniques and ventilatory and fluid management, progress in surgery and anesthesia. However, even some obstetric interventions-screening for asymptomatic bacteriuria, antenatal corticosteroid, prophylactic progestagen, prophylaxis for group B streptococcus, contributed to the decline in mortality. Because of the heavy burden of morbidity, disability, and mortality for premature babies and their families, the decreased productivity and excess costs for society, the main goal is to prevent premature births through an optimal prenatal care for all the women and to prevent bad outcome through organized systems of perinatal care in which mothers at risk are looked after in institutions with obstetric and neonatal specialists and appropriate equipment than can care for the baby. Specialized neonatal transport, when needed, is also an important tool. Further, pregnancy is a time of great enthusiasm for prospective parents. In this time period, a woman can be reached through a multiplicity of mechanisms with interventions aimed at reducing her risk and improving her health and the health of her unborn baby. It is important to reach this goal through the optimal use of known interventions and continued researches. Furthermore, pediatricians can aid the transition to adult health care by being aware of the nutritional, cardiovascular, respiratory, motor, cognitive, psychiatric and functional outcomes of ex-preterm babies that reach adulthood. This global action will give a better start in life for a new generation of newborns and a better outcome on the societal basis.
| References | | |
| 1. | WHO. Preterm Birth; 2012. Available from: http://www.who.int. [Last accessed on 2015 Jan 30].  |
| 2. | Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: A systematic analysis and implications. Lancet 2012;379:2162-72. |
| 3. | Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:75-84. |
| 4. | Shennan AH, Bewley S. Why should preterm births be rising? BMJ 2006;332:924-5. [ PUBMED] |
| 5. | World Health Organization . Born Too Soon: The Global Action Report on Preterm Birth. Geneva: World Health Organization; 2012. |
| 6. | Lisonkova S, Hutcheon JA, Joseph KS. Temporal trends in neonatal outcomes following iatrogenic preterm delivery. BMC Pregnancy Childbirth 2011;11:39. |
| 7. | Steer P. The epidemiology of preterm labour. BJOG 2005;112 Suppl 1:1-3. |
| 8. | Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med 2010;362:529-35. |
| 9. | Menon R. Spontaneous preterm birth, a clinical dilemma: Etiologic, pathophysiologic and genetic heterogeneities and racial disparity. Acta Obstet Gynecol Scand 2008;87:590-600. |
| 10. | Plunkett J, Muglia LJ. Genetic contributions to preterm birth: Implications from epidemiological and genetic association studies. Ann Med 2008;40:167-95. |
| 11. | Mercer BM, Goldenberg RL, Meis PJ, Moawad AH, Shellhaas C, Das A, et al. The preterm prediction study: Effect of gestational age and cause of preterm birth on subsequent obstetric outcome. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1999;181:1216-21. |
| 12. | Clausson B, Lichtenstein P, Cnattingius S. Genetic influence on birthweight and gestational length determined by studies in offspring of twins. BJOG 2000;107:375-81. |
| 13. | Simhan HN. Preterm birth is the leading cause of neonatal mortality and is responsible for roughly one-half of long-term neurologic sequelae. Am J Obstet Gynecol 2010;202:407-8. [ PUBMED] |
| 14. | Engle WA, Tomashek KM, Wallman C, Committee on Fetus and Newborn, American Academy of Pediatrics. "Late-preterm" infants: A population at risk. Pediatrics 2007;120:1390-401. |
| 15. | ACOG Committee Opinion No 404. American college of obstetricians and gynecologist. Obstet Gynecol 2008;111:1029-32. |
| 16. | MacDonald H, American Academy of Pediatrics. Committee on Fetus and Newborn. Perinatal care at the threshold of viability. Pediatrics 2002;110:1024-7. |
| 17. | American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrcian-Gynecologists: Number 38, September 2002. Perinatal care at the threshold of viability. Obstet Gynecol 2002;100:617-24. |
| 18. | |
| 19. | Vavasseur C, Foran A, Murphy JF. Consensus statements on the borderlands of neonatal viability: From uncertainty to grey areas. Ir Med J 2007;100:561-4. |
| 20. | Greisen G. Managing births at the limit of viability: The Danish experience. Semin Fetal Neonatal Med 2004;9:453-7. |
| 21. | Pignotti MS. Periviable newborns around the globe. Where we are now, and what the future may hold? Curr Pediatr Rev 2013;9:1-3. |
| 22. | Draper ES. Evaluating and comparing neonatal outcomes. Arch Dis Child Fetal Neonatal Ed 2010;95:F158-9. |
| 23. | Draper ES, Field DJ. Epidemiology of prematurity - How valid are comparisons of neonatal outcomes? Semin Fetal Neonatal Med 2007;12:337-43. |
| 24. | Platt MJ. Outcomes in preterm infants. Public Health 2014;128:399-403. |
| 25. | Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: Outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics 2000;106:659-71. |
| 26. | Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES. Short term outcomes after extreme preterm birth in England: Comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 2012;345:e7976. |
| 27. | Kmietowicz Z. Incidence of severe disability among very premature babies has not changed for a decade. BMJ 2012;345:e8264. [ PUBMED] |
| 28. | Seaton SE, King S, Manktelow BN, Draper ES, Field DJ. Babies born at the threshold of viability: Changes in survival and workload over 20 years. Arch Dis Child Fetal Neonatal Ed 2013;98:F15-20. |
| 29. | Halmøy A, Klungsøyr K, Skjærven R, Haavik J. Pre- and perinatal risk factors in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 2012;71:474-81. |
| 30. | Volpe JJ. Encephalopathy of prematurity includes neuronal abnormalities. Pediatrics 2005;116:221-5. |
| 31. | Khwaja O, Volpe JJ. Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed 2008;93:F153-61. |
| 32. | Spittle AJ, Orton J. Cerebral palsy and developmental coordination disorder in children born preterm. Semin Fetal Neonatal Med 2014;19:84-9. |
| 33. | Johnson S, Marlow N. Preterm birth and childhood psychiatric disorders. Pediatr Res 2011;69:11R-8. |
| 34. | Johnson S, Wolke D. Behavioural outcomes and psychopathology during adolescence. Early Hum Dev 2013;89:199-207. |
| 35. | Marconi AM. 37% of child survivors of intrauterine or neonatal insults experience at least one long-term sequela, the most common being neurodevelopmental delay. Evid Based Nurs 2013;16:75-6. |
| 36. | Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet 2008;371:261-9. |
| 37. | De Jong M, Verhoeven M, van Baar AL. School outcome, cognitive functioning, and behaviour problems in moderate and late preterm children and adults: A review. Semin Fetal Neonatal Med 2012;17:163-9. |
| 38. | Vohr B. Speech and language outcomes of very preterm infants. Semin Fetal Neonatal Med 2014;19:78-83. |
| 39. | Roberts G, Cheong JL. Long-term growth and general health for the tiniest or most immature infants. Semin Fetal Neonatal Med 2014;19:118-24. |
| 40. | Farstad T, Bratlid D, Medbø S, Markestad T. Norwegian Extreme Prematurity Study Group. Bronchopulmonary dysplasia-prevalence, severity and predictive factors in a national cohort of extremely premature infants. Acta Paediatr 2011;100:53-8. |
| 41. | Gibson AM, Doyle LW. Respiratory outcomes for the tiniest or most immature infants. Semin Fetal Neonatal Med 2014;19:105-11. |
| 42. | Pike K, Brocklehurst P, Jones D, Kenyon S, Salt A, Taylor D, et al. Outcomes at 7 years for babies who developed neonatal necrotising enterocolitis: The ORACLE Children Study. Arch Dis Child Fetal Neonatal Ed 2012;97:F318-22. |
| 43. | Saigal S. Quality of life of former premature infants during adolescence and beyond. Early Hum Dev 2013;89:209-13. |
| 44. | Hack M, Flannery DJ, Schluchter M, Cartar L, Borawski E, Klein N. Outcomes in young adulthood for very-low-birth-weight infants. N Engl J Med 2002;346:149-57. |
| 45. | Kajantie E, Hovi P. Is very preterm birth a risk factor for adult cardiometabolic disease? Semin Fetal Neonatal Med 2014;19:112-7. |
| 46. | Doyle LW, Anderson PJ. Adult outcome of extremely preterm infants. Pediatrics 2010;126:342-51. |
| 47. | Hack M. Adult outcomes of preterm children. J Dev Behav Pediatr 2009;30:460-70. |
| 48. | Nosarti C, Reichenberg A, Murray RM, Cnattingius S, Lambe MP, Yin L, et al. Preterm birth and psychiatric disorders in young adult life. Arch Gen Psychiatry 2012;69:E1-8. |
| 49. | Saigal S. Functional outcomes of very premature infants into adulthood. Semin Fetal Neonatal Med 2014;19:125-30. |
| 50. | Treyvaud K. Parent and family outcomes following very preterm or very low birth weight birth: A review. Semin Fetal Neonatal Med 2014;19:131-5. |
| 51. | Feldman R. Maternal versus child risk and the development of parent-child and family relationships in five high-risk populations. Dev Psychopathol 2007;19:293-312. |
| 52. | Pignotti MS, Donzelli G. Perinatal care at the threshold of viability: An international comparison of practical guidelines for the treatment of extremely preterm births. Pediatrics 2008;121:e193-8. |
| 53. | Pignotti MS. Extremely preterm births: Recommendations for treatment in European countries. Arch Dis Child Fetal Neonatal Ed 2008;93:F403-6. |
| 54. | Jefferies AL, Kirpalani HM, Canadian Paediatric Society Fetus and Newborn Committee. Counselling and management for anticipated extremely preterm birth. Paediatr Child Health 2012;17:443-6. |
| 55. | Berger TM, Bernet V, El Alama S, Fauchère JC, Hösli I, Irion O, et al. Perinatal care at the limit of viability between 22 and 26 completed weeks of gestation in Switzerland 2011 revision of the Swiss recommendations. Swiss Med Wkly 2011;141:w13280. |
| 56. | Al-Alaiyan S. Call to establish a national lower limit of viability. Ann Saudi Med 2008;28:1-3. |
| 57. | Iams JD, Romero R, Culhane JF, Goldenberg RL. Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet 2008;371:164-75. |
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