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{{limitedgeographicscope}}
{{DiseaseDisorder infobox |
Name = Premature birth |
ICD10 = {{ICD10|O|60|1|o|60}}, {{ICD10|P|07|3|p|05}} |
ICD9 = {{ICD9|644}}, {{ICD9|765}} |
ICDO = |
Image = |
Caption = |
OMIM = |
OMIM_mult = |
MedlinePlus = 001562 |
eMedicineSubj = ped |
eMedicineTopic = 1889 |
DiseasesDB = 10589 |
}}

'''Premature birth''' (also known as '''preterm birth''') is the [[birth]] of a [[baby]] before the standard period of [[pregnancy]] is completed. In most systems of human pregnancy, prematurity is considered to occur when the [[baby]] is born sooner than 37 weeks after the beginning of the last menstrual period (LMP). The opposite condition, [[postmature birth]], is defined as birth more than 42 weeks after the LMP.

==Overview==
The standard length of a human [[gestation]] is 266 days. However, for convenience most timing is based on the LMP, with [[fertilisation|conception]] being assumed to occur approximately 14 days after the LMP, making a standard term pregnancy 280 days or 40 weeks. Premature or preterm birth (the babies are called premies) is defined medically as [[childbirth]] occurring earlier than 37 completed weeks of pregnancy. Approximately 12 percent of babies in the [[United States]] — or 1 in 8 — are born prematurely each year.<ref>Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Kirmeyer S. “Births: Final Data for 2004.” ''National Vital Statistics Reports'', vol. 55, no 1. Hyattsville, Maryland: National Center for Health Statistics, 2006.</ref> In [[2003]], more than 490,000 babies in the U.S. were born prematurely. Worldwide rates of prematurity are more difficult to obtain as the lack of widespread professional [[obstetrics|obstetric]] care in developing regions makes determination of [[gestational age]] less reliable. The [[World Health Organization]] instead tracks rates of low [[birth weight]], which occurred in 16.5 percent of births in less developed regions in 2000.<ref>[http://www.who.int/research/en/ WHO | Data and statistics<!-- Bot generated title -->]</ref> It is estimated that one-third of these low birth weight deliveries are due to premature delivery.

The shorter the term of pregnancy, the greater the risks of complications. Infants born prematurely have an increased risk of death in the first year of life ([[infant mortality]]), with most of that occurring in the first month of life ([[neonatal mortality]]). Worldwide, prematurity accounts for 10% of neonatal mortality, or around 500,000 deaths per year.<ref>Child Health Research Project Special Report. "Reducing Perinatal and Neonatal Mortality." ''Meeting Report'', vol. 3, no 1. Baltimore, Maryland, May 10–12, 1999.</ref> In the U.S. where many infections and other causes of neonatal death have been markedly reduced, prematurity is the leading cause of neonatal mortality at 25%.<ref>Mathew TJ and MacDorman MF. "Infant Mortality Statistics from the 2003 Period Linked Birth/Infant Death Data Set." ''National Vital Statistics Reports'', vol. 54, no 16. Hyattsville, Maryland: National Center for Health Statistics, 2006.</ref> Prematurely born infants are also at greater risk for developing serious health problems such as [[cerebral palsy]], [[bronchopulmonary dysplasia|chronic lung disease]], [[gastrointestinal]] problems, [[mental retardation]], [[blindness|vision]] or [[deafness|hearing loss]]<ref>March of Dimes. ''[http://www.marchofdimes.com/files/PremFactSheetFinalOct2006.pdf The Growing Problem of Prematurity]''. October 2006.</ref> and are more susceptible to developing [[Clinical depression|depression]] as teenagers.<ref>The Age ''[http://www.theage.com.au/articles/2004/05/03/1083436541757.html Depression Linked to Premature Birth].'' May 2004.</ref>

Although there are several known risk factors for prematurity (see below), nearly half of all premature births have no known cause. When conditions permit, doctors may attempt to stop premature labor, so that the pregnancy can have a chance to continue to full term, thereby increasing the baby's chances of health and survival. However, there is currently no reliable means to stop or prevent preterm labor in all cases. In fact, the rate of preterm births in the United States has increased 30% in the past two decades.<ref>Mayo Clinic. ''[http://www.mayoclinic.com/health/premature-birth/DS00137/DSECTION=1 Premature Birth].'' 6 November 2006.</ref>

In developed countries premature infants are usually cared for in a [[Neonatal Intensive Care Unit]] (NICU). The physicians who specialize in the care of very sick or premature babies are known as [[neonatology|neonatologists]]. In the NICU, premature babies are kept under radiant warmers or in [[incubator]]s (also called isolettes), which are [[bassinet]]s enclosed in plastic with climate control equipment designed to keep them warm and limit their exposure to germs. Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, [[oxygenation]], and [[Electroencephalography|brain activity]]. Treatments may include fluids and nutrition through [[intravenous therapy|intravenous]] catheters, [[oxygen]] supplementation, [[mechanical ventilation]] support, and medications. In developing countries where advanced equipment and even electricity may not be available or reliable, simple measures such as ''[[kangaroo care]]'' (skin to skin warming), encouraging [[breastfeeding]], and basic infection control measures can significantly reduce preterm [[morbidity]] and mortality.

"Ex-premies" is the term given to preterm infants born before the normal 37 weeks gestation.<ref>Burton, Edward M. and Brody, Alan S.,''Essentials of Pediatric Radiology'', Thieme, ISBN 0-865-77802-7</ref>

== Factors ==
There are many different factors that may contribute to a preterm birth.

Factors related to maternal disease or condition that have been shown to increase the risk of preterm birth, with associated odds ratio (OR) when known include:

*Chromosomal abnormalities; Dr. Aaron Caughey, a perinatologist at UCSF, states: "...it's important to note that the majority of miscarriages — up to 80 percent — happen due to chromosomal abnormalities that have nothing to do with the mother's behavior. The last thing women who have had miscarriages need to do is blame themselves...." source: ''San Francisco Chronicle''

*[[high blood pressure]] (OR = 4.06)<ref name="pmid9491013">{{cite journal |author=Goldenberg RL, Iams JD, Mercer BM, ''et al'' |title=The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network |journal=Am J Public Health |volume=88 |issue=2 |pages=233–8 |year=1998 |pmid=9491013 |doi=}}</ref>

*[[pre-eclampsia]] (OR = 4.0)<ref name="pmid17464860">{{cite journal |author=Bánhidy F, Acs N, Puhó EH, Czeizel AE |title=Pregnancy complications and birth outcomes of pregnant women with urinary tract infections and related drug treatments |journal=Scand. J. Infect. Dis. |volume=39 |issue=5 |pages=390–7 |year=2007 |pmid=17464860 |doi=10.1080/00365540601087566 |url=http://www.informaworld.com/openurl?genre=article&doi=10.1080/00365540601087566&magic=pubmed||1B69BA326FFE69C3F0A8F227DF8201D0}}</ref>

*age > 35 (OR = 1.8)<ref name="pmid9846665">{{cite journal |author=Martius JA, Steck T, Oehler MK, Wulf KH |title=Risk factors associated with preterm (<37+0 weeks) and early preterm birth (<32+0 weeks): univariate and multivariate analysis of 106 345 singleton births from the 1994 statewide perinatal survey of Bavaria |journal=Eur. J. Obstet. Gynecol. Reprod. Biol. |volume=80 |issue=2 |pages=183–9 |year=1998 |pmid=9846665 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0301211598001304}}</ref>

*age < 18 (OR = 3.4)<ref name="pmid9846665"> </ref>

*short cervix<ref name="pmid9491013"> </ref> (the strongest predictor of premature birth)<ref>To MS, Skentou CA, Royston P, Yu CKH, Nicolaides KH. Prediction of patient-specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: a population-based prospective study. Ultra Obstet Gynecol 2006; 27: 362–367.</ref><ref name = "Fonseca-p462">Fonseca et al. Progesterone and the risk of preterm birth among women with a short cervix. NEJM 2007; vol 357, no 5, pg 462–469.</ref><ref name = "Romero-675">Romero R. Prevention of sponatneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. Ultrasound Obstet Gynecol 2007; 30: 675–686. http://www3.interscience.wiley.com/journal/99020267/home free download</ref>

*maternal diabetes<ref name="pmid16118366">{{cite journal |author=Rosenberg TJ, Garbers S, Lipkind H, Chiasson MA |title=Maternal obesity and diabetes as risk factors for adverse pregnancy outcomes: differences among 4 racial/ethnic groups |journal=Am J Public Health |volume=95 |issue=9 |pages=1545–51 |year=2005 |pmid=16118366 |doi=10.2105/AJPH.2005.065680}}</ref>

*anxiety<ref name="pmid12505886">{{cite journal |author=Dole N, Savitz DA, Hertz-Picciotto I, Siega-Riz AM, McMahon MJ, Buekens P |title=Maternal stress and preterm birth |journal=Am. J. Epidemiol. |volume=157 |issue=1 |pages=14–24 |year=2003 |pmid=12505886 |doi= |url=http://171.66.121.65/cgi/reprint/157/1/14 |doi=10.1093/aje/kwf176}}</ref>

*[[periodontal disease]] (OR = 4.45)<ref>Jeffcoat, Marjorie K., Nico C. Geurs, Michael S. Reddy, Suzanne P. Cliver, Robert L. Goldenberg, and John C. Hauth. "Periodontal Infection and Preterm Birth." The Journal of the American Dental Association 132 (2001): 875–880. [[25 April]] [[2007]] [http://jada.ada.org/cgi/content/abstract/132/7/875].</ref>

Whether or not [[urinary tract]] infections directly cause preterm birth is uncertain, however, it is known that urinary tract infections increase pre-eclampsia, which as stated above, increases the risk of preterm birth. [[Sexually transmitted disease]] (STD), [[Beta strep|Beta Strep]], kidney disease, and uterine infections are also suspected of increasing the risk of preterm birth.

Adequate maternal [[nutrition]] is important to fetal development and a diet low in saturated fat and cholesterol may help reduce the risk of a preterm delivery.<ref>"Cholesterol Lowering Diet for Pregnant Women May Help Prevent Preterm Birth." BMJ: British Medical Journal 331 (2005): 1093. [[1 May]] [[2007]] [http://web.ebscohost.com/ehost/detail?vid=4&hid=117&sid=fe387f34-508b-46a8-8f32-ff975c1297a4%40sessionmgr9].</ref>

Factors related to pregnancy history that have been shown to increase the risk of preterm birth include:
*prior preterm delivery (OR = 2.79)
*prior induced abortion (OR = 1.6)
*antepartum hemorrhage / vaginal bleeding during labor
*prior [[miscarriage]]<ref name="pmid9491013"> </ref>


Multiple pregnancies ([[twins]], triplets, etc.) are another significant factor in preterm birth. The March of Dimes Multicenter Prematurity and Prevention Study found that 54% of twins were delivered preterm vs. 9.6% of singleton births.<ref name="pmid7898832">{{cite journal |author=Gardner MO, Goldenberg RL, Cliver SP, Tucker JM, Nelson KG, Copper RL |title=The origin and outcome of preterm twin pregnancies |journal=Obstet Gynecol |volume=85 |issue=4 |pages=553–7 |year=1995 |pmid=7898832 |doi=10.1016/0029-7844(94)00455-M |url=http://www.greenjournal.org/cgi/pmidlookup?view=long&pmid=7898832}}</ref>

Women who have tried to conceive for more than a year before getting pregnant are at a higher risk for premature birth. A recent study done by Dr. Olga Basso of the University of [[Aarhus]] in [[Denmark]] and Dr. Donna Baird of the U.S. National Institute of Environmental Health Sciences suggests that women who had difficulty conceiving were about 40 percent higher risk of preterm birth than those who had conceived easily.

Finally, the use of [[tobacco]] and [[alcohol]] during pregnancy also increases the chance of preterm delivery. Tobacco is the most commonly abused drug during pregnancy and also contributes significantly to low birth weight delivery.<ref>Shiono, Patricia H., Mark A. Klebanoff, Robert P. Nugent, Mary F. Cotch, Diana G. Wilkins, Douglas E. Rollins, Christopher J. Carey, and Richard E. Behrman. "Fetus-Placenta-Newborn: the Impact of Cocaine and Marijuana Use on Low Birth Weight and Preterm Birth: a Multicenter Study." American Journal of Obsetrics and Gynecology 172 (1995): 19–27. [[1 May]] [[2007]] [http://pt.wkhealth.com/pt/re/ajog/abstract.00000447-199501000-00003.htm;jsessionid=GGQfDBDtJTWynh5ZX5cT2f1bw72GDVwyBbjh7q1rvNqj8b2L3mkQ!-1870145763!-949856144!8091!-1].
</ref><ref>Parazzini, F, L. Chatenoud, M. Surace, L. Tozzi, B. Salerio, G. Bettoni, and G. Benzi. "Moderate Alcohol Drinking and Risk of Preterm Birth." European Journal of Clinical Nutrition 57 (2003): 1345. [[1 May]] [[2007]] [http://web.ebscohost.com/ehost/detail?vid=3&hid=3&sid=afc585c7-2d1e-43e5-87b5-f9c746caf1fc%40sessionmgr8].</ref>
== Prevention of preterm birth ==
Recent research has identified possible methods to '''''prevent''''' preterm birth, pre-eclampsia/eclampsia, premature rupture of membranes, and preterm labor.

These include self-care methods to reduce infections, nutritional and psychological interventions, and the control of preterm birth risk factors (e.g. working long hours while standing on feet, carbon monoxide exposure, domestic abuse, and other factors). Injection with a form of progesterone (17 alpha-hydroxyprogesterone caproate) although the safety of this treatment for the fetus has been questioned by the FDA and its expert panel due to an associated increase in miscarriage and fetal death<ref>[http://www.fda.gov/ohrms/dockets/ac/cder06.html#rhdac Advisory Committees: CDER 2006 Meeting Documents<!-- Bot generated title -->]</ref>, the use of vaginal progesterone<ref name = "Fonseca-p462"/><ref name = "Romero-675"/> ,taking fish oil supplements, and self-monitoring vaginal PH followed by yogurt treatment or Clindamycin treatment if the PH was too high all seem to be effective at reducing the risk of preterm birth.<ref> Lamont RF and Jaggat AN. Emerging drug therapies for preventing spontaneous preterm labor and preterm birth. Expert Opin Investig Drugs. 2007 16:337–45. PMID 17302528
</ref><ref> Hoyme UB and Saling E. Efficient prematurity prevention is possible by pH-self measurement and immediate therapy of threatening ascending infection. Eur J Obstet Gynecol Reprod Biol. 2004 115:148–53. PMID 15262346
</ref> This research is quite new; however, doctors using these newer strategies have obtained preterm birth rates as low as 1 to 2%, compared to the 11 to 16% currently in the US. {{Fact|date=February 2007}}

Although short term use of folic acid may not have an effect, genetic variation in folate metabolism affects prematurity, and a recent report suggests that usage by mothers for more than a year before birth can reduce premature birth by 50 to 70 percent.<ref name="Dwight Rouse">{{cite web|url=http://timesreporter.com/index.php?ID=78878&r=0|title=Study: Giving moms magnesium sulfate cuts risk of cerebral palsy in extreme premature babies}}<!-- this is also a reference for the folate result presented at the conference --></ref><ref>PMID 17074544</ref>

== Symptoms and indications ==
The symptoms of an imminent premature birth include:
*Four or more uterine [[Contraction (childbirth)|contraction]]s in one hour, before 37 weeks' gestation.
*A watery discharge from the vagina, which may indicate premature rupture of the membranes surrounding the baby.
*Pressure in the [[pelvis]] or the sensation that the baby has "dropped".
*[[Menstruation|Menstrual cramps]] or abdominal pain.
*Pain or rhythmic tightening in lower abdomen or back.
*Vaginal spotting or bleeding.

== Maternal treatments ==
There are two tactics that can be used to deal with a potential premature birth: delay the arrival of birth as much as possible, or prepare the prospectively premature fetus for arrival. Both of these tactics may be used simultaneously.

Delaying the premature birth from occurring is typically the most favored option. This gives the fetus or fetuses as much time as possible to mature in the womb. There are a number of techniques that can be used to try to accomplish this. The first resort is usually complete bed rest. Maintaining a horizontal position reduces pressure on the [[cervix]], which may allow it to stay lengthened longer, and avoiding unnecessary movement may reduce uterine irritation, which can lead to contractions. Likewise, proper nutrition and especially hydration are important: dehydration can lead to premature uterine contractions. In a hospital setting, a drug-free IV drip may be used to try to stop premature labor simply by improving the mother's hydration. Lastly, there are anti-contraction medications ([[tocolytic]]s), such as [[ritodrine]], [[fenoterol]], [[nifedipine]] and [[atosiban]], although these do not appear to have more than a short-term effect on delaying delivery.

Premature birth can not always be prevented. Severely premature infants may have underdeveloped lungs, because they are not yet producing their own [[surfactant]]. This can lead directly to [[Infant respiratory distress syndrome|Respiratory Distress Syndrome]], also called hyaline membrane disease, in the neonate. To try to reduce the risk of this outcome, pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of [[glucocorticoids]], a steroid that crosses the placental barrier and stimulates growth in the lungs of the fetus. Typical glucocorticoids that would be administered in this context are [[betamethasone]] or [[dexamethasone]], often when the fetus has reached viability at 23 weeks. In cases where premature birth is imminent, a second "rescue" course of steroids may be administered 12 to 24 hours before the anticipated birth. There is no research consensus on the efficacy and side-effects of a second course of steroids, but the consequences of RDS are so severe that a second course is often viewed as worth the risk.

Research reported at the 2008 conference of the Society for Maternal-Fetal Medicine suggests that administration of [[magnesium sulfate]] (Epsom salt) to women just before premature birth can cut the rate of [[cerebral palsy]] in half. While the compound is cheap and safe, it may make mothers and infants groggy, and details are pending scientific publication.<ref name="Dwight Rouse" />

== Newborn complications ==

Premature infants show physical signs of their prematurity and may develop other problems as well. These include, but are not limited to, the following:

Neurologic
*[[Apnea of prematurity]]
*Hypoxic-ischemic encephalopathy (HIE)
*[[Intra-axial hematoma|Intracranial hemorrhage]]
*[[Retinopathy of prematurity]] (ROP)
*[[Developmental disability]]

Cardiovascular
*[[Patent ductus arteriosus]] (PDA)

Respiratory
*[[Infant respiratory distress syndrome|Respiratory distress syndrome]] (RDS or IRDS)
*[[Bronchopulmonary dysplasia|Chronic lung disease]] (previously called bronchopulmonary dysplasia or BPD)

Gastrointestinal / metabolic
*[[Hypoglycemia#Hypoglycemia in newborn infants|Hypoglycemia]]
*Feeding difficulties
*[[Rickets]] of prematurity
*[[Hypocalcemia]]
*[[Inguinal hernia]]
*[[Necrotizing enterocolitis]] (NEC)

Hematologic
*[[Anemia of prematurity]]
*[[Thrombocytopenia]]
*[[Hyperbilirubinemia]] (jaundice)

Infectious
*[[Sepsis]]
*[[Urinary tract infection]] {{ref|1}}


[[Image:Miscarriage-Pregnancy timeline.png|800px|center]]

The earliest [[gestational age]] at which the infant has at least a 50% chance of survival is referred to as the [[limit of viability]]. As NICU care has improved over the last 40 years, viability has reduced to approximately 24 weeks,<ref name="pmid16396856">{{cite journal |author=Kaempf JW, Tomlinson M, Arduza C, ''et al'' |title=Medical staff guidelines for periviability pregnancy counseling and medical treatment of extremely premature infants |journal=Pediatrics |volume=117 |issue=1 |pages=22–9 |year=2006 |pmid=16396856 |doi=10.1542/peds.2004–2547 |url=http://pediatrics.aappublications.org/cgi/content/full/117/1/22}} — in particular see [http://pediatrics.aappublications.org/cgi/content-nw/full/117/1/22/T1 TABLE 1 Survival and Neurologic Disability Rates Among Extremely Premature Infants]</ref><ref name="pmid18240080">{{cite journal |author=Morgan MA, Goldenberg RL, Schulkin J |title=Obstetrician-gynecologists' practices regarding preterm birth at the limit of viability |journal=J. Matern. Fetal. Neonatal. Med. |volume=21 |issue=2 |pages=115–21 |year=2008 |pmid=18240080 |doi=10.1080/14767050701866971}}</ref> although rare survivors have been documented as early as 21 weeks.[http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20070220/baby_premature_070219/20070220?hub=CTVNewsAt11] Though this date is controversial as gestation in this case was measured from the date of conception rather than the date of her mother's last menstrual period gestation appear 2 weeks less than if calculated by the more common method<ref name="abchealth">{{http://abcnews.go.com/Health/story?id=2890242&page=1}}</ref>. As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are [[medical ethics|ethical]] controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the [[abortion]] debate.

Some of the complications related to prematurity are not apparent until years after the birth. For example, children who were born prematurely (especially if born less than 1,500 grams) have a higher likelihood of having behavioral problems, delays in motor development, and difficulties in school. Specifically these problems can be described as being within the [[Executive system|executive]] domain and have been speculated to arise due to decreased [[myelinization]] of the [[frontal lobes]].<ref>Böhm, Katz-Salamon, Smedler, Lagercrantz & Forssberg: "Developmental Risks and Protective Factors for Influencing cognitive outcome at 5,5 years of age in very-low-birthweight children". Developmental Medicine & Child Neurology 2002, 44: 508–516.</ref> Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists.

== Treatment measures for a premature infant ==
The required care for premature infants differs greatly depending on the child's gestational age, birth weight, and overall maturity. Measures common among extremely premature infants include:
*Placing the infant in a warmer or isolette. Premature infants are easily susceptible to cold-stress or [[hypothermia]] and infection, and preventing these is a key priority.
*Infants under 32 weeks typically do not produce enough [[Pulmonary surfactant|surfactant]] in their lungs to enable them to breathe on their own. In these cases, surfactant will be administered to assist them.
*A [[endotracheal tube|breathing tube]] may be inserted in the infant's trachea, and a ventilator and supplemental oxygen may be used.
*Adequate nutrition, via a [[feeding tube]] or, in extremely premature infants, intravenously. If a feeding tube is used, expressed [[breast milk]] from the mother or a [[Human milk banking in North America|breastmilk bank]] can be used, which lowers the risk of infections such as [[necrotizing enterocolitis]].

==Records==

James Elgin Gill (born on [[20 May]] [[1987]] in [[Ottawa]], [[Canada]]) was the earliest premature baby in the world. He was 128 days premature (21 weeks and 5 days gestation) and weighed 1 lb. 6 oz. (624 g). He survived and is quite healthy.<ref name="titlePowell's Books — Guinness World Records 2004 (Guinness Book of Records) by">{{cite web |url=http://www.powells.com/biblio?show=0553587129&page=excerpt? |title=Powell's Books — Guinness World Records 2004 (Guinness Book of Records) by |accessdate=2007-11-28 |format= |work=}}</ref><ref name="titleMiracle child">{{cite web |url=http://www.canada.com/topics/bodyandhealth/story.html?id=db8f33ab-33e9-429f-bedc-b6ca80f61bdc |title=Miracle child |accessdate=2007-11-28 |format= |work=}}</ref>

Amillia Taylor is also often cited as the most-premature baby.<ref name="bbcAmillia">{{cite news | url = http://news.bbc.co.uk/1/hi/world/americas/6384621.stm | title = Most-premature baby allowed home | publisher = BBC News | date = [[2007-02-21]] | accessdate=2007-05-05 }}</ref> She was born on [[24 October]] [[2006]] in [[Miami]], [[Florida]], at 21 weeks and 6 days gestation.<ref name="titletrithuc.thanhnienkhcn.org.vn">{{cite web |url=http://210.245.61.173/en/detail.php? |title=trithuc.thanhnienkhcn.org.vn |accessdate=2007-11-28 |format= |work=}}</ref> Though this report has created some confusion her gestation was measured from the date of conception (through IVF) rather than the date of her mother's last menstrual period making her appear 2 weeks younger than if gestation was calculated by the more common method<ref name="abchealth2">{{http://abcnews.go.com/Health/story?id=2890242&page=1}}</ref>. At birth she was 9 inches (23 cm) long and weighed 10 ounces (283 grams).<ref name="bbcAmillia">{{cite news | url = http://news.bbc.co.uk/1/hi/world/americas/6384621.stm | title = Most-premature baby allowed home | publisher = BBC News | date = [[2007-02-21]] | accessdate=2007-05-05 }}</ref> She suffered [[digestion|digestive]] and [[Respiratory system|respiratory]] problems, together with a [[brain]] [[bleeding|hemorrhage]]. She was discharged from the Baptist Children's Hospital on [[20 February]] [[2007]].<ref name="bbcAmillia"/>

The record for the smallest premature baby to survive was held for some time by Madeline Mann, who was born at 26 weeks weighing 9.9 oz (280 g) and 9.5 inches (24 cm) long.<ref name="titleThe Hindu : A little miracle called Madeline">{{cite web |url=http://www.hindu.com/seta/2004/08/26/stories/2004082600411400.htm |title=The Hindu : A little miracle called Madeline |accessdate=2007-11-28 |format= |work=}}</ref> This record was broken in [[September 2004]] by Rumaisa Rahman, who was born in the same hospital<ref name="titleWorld's Smallest Baby Goes Home, Cellphone-Sized Baby Is Discharged From Hospital — CBS News">{{cite web |url=http://www.cbsnews.com/stories/2005/02/08/health/main672488.shtml |title=World's Smallest Baby Goes Home, Cellphone-Sized Baby Is Discharged From Hospital — CBS News |accessdate=2007-11-28 |format= |work=}}</ref> at 25 weeks gestation. At birth she was eight inches (20 cm) long and weighed 244 [[gram]]s (8.6 [[ounce]]s). Her twin sister was also a small baby, weighing 563 grams (1 pound 4 ounces) at birth. During [[pregnancy]] their mother had suffered from [[pre-eclampsia]], which causes dangerously high [[blood pressure]] putting the baby into distress and leading to birth by [[caesarean section]]. The larger twin left the hospital at the end of December, while the smaller remained there until [[10 February]], [[2005]] by which time her weight had increased to 1.18 kg (2 pounds 10 ounces).<ref>CBS News. [[8 February]] [[2005]]. [http://www.cbsnews.com/stories/2005/02/08/health/main672488.shtml World's Smallest Baby Goes Home]</ref> Generally healthy, the twins had to undergo laser [[eye]] surgery to correct visual problems, a common occurrence among premature babies.

Historical figures who were born prematurely include [[Johannes Kepler]] (born in 1571 at 7 months gestation), [[Isaac Newton]] (born in 1643, small enough to fit into a [[quart]] mug, according to his [[Hannah Ayscough|mother]]), [[Winston Churchill]] (born in 1874 at 7 months gestation), and [[Anna Pavlova]] (born in 1885 at 7 months gestation).<ref>Raju, T. N. K. (1980). [http://www.neonatology.org/classics/mj1980/ch28.html Some Famous "High Risk" Newborn Babies]. In ''Historical Review and Recent Advances in Neonatal and Perinatal Medicine''. Retrieved June 23, 2006.</ref>

==See also==

*[[Macrophage-activation syndrome]]
*[[WalkAmerica]] an annual walking-for-charity event that has raised more than $1.7 billion since 1970 to prevent premature birth

==References==
{{reflist|2}}

==External links==
* [http://www.shareyourstory.org/ Share Your Story] — online community for NICU families, from the March of Dimes
* [http://www.aboutkidshealth.ca/prematurebabies Premature Babies Resource Centre from AboutKidsHealth.ca] Information about the causes of prematurity, the challenges of premature birth, the development of the baby, and the long-term implication of prematurity.
* [http://www.prematurity.org/ Prematurity] — resource site for parents of premature infants and children
* [http://www.littlesteps.co.za/ Little Steps] — research-based, resource site for parents with premature infants in NICU and information and training courses for healthcare professionals. Based in South Africa
* [http://www.kidshealth.org/parent/growth/growing/preemies.html Primer on Preemies] — from the Nemours Foundation
* [http://www.gurbutt.co.uk/ Supporting Parents of Older Premature Children in the UK] - Advocating early educational intervention: assessment and provision
{{Pathology of pregnancy, childbirth and the puerperium}}
{{Certain conditions originating in the perinatal period}}

[[Category:Childbirth]]

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[[ja:早産]]
[[no:Ufullbåret barn]]
[[pl:Wcześniactwo]]
[[ru:Недоношенный ребёнок]]
[[fi:Keskonen]]
[[sv:Prematur]]
[[tr:Erken doğum]]
[[zh:早產]]

Revision as of 17:39, 10 June 2008

Preterm birth
SpecialtyObstetrics and gynaecology Edit this on Wikidata

Premature birth (also known as preterm birth) is the birth of a baby before the standard period of pregnancy is completed. In most systems of human pregnancy, prematurity is considered to occur when the baby is born sooner than 37 weeks after the beginning of the last menstrual period (LMP). The opposite condition, postmature birth, is defined as birth more than 42 weeks after the LMP.

Overview

The standard length of a human gestation is 266 days. However, for convenience most timing is based on the LMP, with conception being assumed to occur approximately 14 days after the LMP, making a standard term pregnancy 280 days or 40 weeks. Premature or preterm birth (the babies are called premies) is defined medically as childbirth occurring earlier than 37 completed weeks of pregnancy. Approximately 12 percent of babies in the United States — or 1 in 8 — are born prematurely each year.[1] In 2003, more than 490,000 babies in the U.S. were born prematurely. Worldwide rates of prematurity are more difficult to obtain as the lack of widespread professional obstetric care in developing regions makes determination of gestational age less reliable. The World Health Organization instead tracks rates of low birth weight, which occurred in 16.5 percent of births in less developed regions in 2000.[2] It is estimated that one-third of these low birth weight deliveries are due to premature delivery.

The shorter the term of pregnancy, the greater the risks of complications. Infants born prematurely have an increased risk of death in the first year of life (infant mortality), with most of that occurring in the first month of life (neonatal mortality). Worldwide, prematurity accounts for 10% of neonatal mortality, or around 500,000 deaths per year.[3] In the U.S. where many infections and other causes of neonatal death have been markedly reduced, prematurity is the leading cause of neonatal mortality at 25%.[4] Prematurely born infants are also at greater risk for developing serious health problems such as cerebral palsy, chronic lung disease, gastrointestinal problems, mental retardation, vision or hearing loss[5] and are more susceptible to developing depression as teenagers.[6]

Although there are several known risk factors for prematurity (see below), nearly half of all premature births have no known cause. When conditions permit, doctors may attempt to stop premature labor, so that the pregnancy can have a chance to continue to full term, thereby increasing the baby's chances of health and survival. However, there is currently no reliable means to stop or prevent preterm labor in all cases. In fact, the rate of preterm births in the United States has increased 30% in the past two decades.[7]

In developed countries premature infants are usually cared for in a Neonatal Intensive Care Unit (NICU). The physicians who specialize in the care of very sick or premature babies are known as neonatologists. In the NICU, premature babies are kept under radiant warmers or in incubators (also called isolettes), which are bassinets enclosed in plastic with climate control equipment designed to keep them warm and limit their exposure to germs. Modern neonatal intensive care involves sophisticated measurement of temperature, respiration, cardiac function, oxygenation, and brain activity. Treatments may include fluids and nutrition through intravenous catheters, oxygen supplementation, mechanical ventilation support, and medications. In developing countries where advanced equipment and even electricity may not be available or reliable, simple measures such as kangaroo care (skin to skin warming), encouraging breastfeeding, and basic infection control measures can significantly reduce preterm morbidity and mortality.

"Ex-premies" is the term given to preterm infants born before the normal 37 weeks gestation.[8]

Factors

There are many different factors that may contribute to a preterm birth.

Factors related to maternal disease or condition that have been shown to increase the risk of preterm birth, with associated odds ratio (OR) when known include:

  • Chromosomal abnormalities; Dr. Aaron Caughey, a perinatologist at UCSF, states: "...it's important to note that the majority of miscarriages — up to 80 percent — happen due to chromosomal abnormalities that have nothing to do with the mother's behavior. The last thing women who have had miscarriages need to do is blame themselves...." source: San Francisco Chronicle
  • age > 35 (OR = 1.8)[11]
  • age < 18 (OR = 3.4)[11]
  • maternal diabetes[15]

Whether or not urinary tract infections directly cause preterm birth is uncertain, however, it is known that urinary tract infections increase pre-eclampsia, which as stated above, increases the risk of preterm birth. Sexually transmitted disease (STD), Beta Strep, kidney disease, and uterine infections are also suspected of increasing the risk of preterm birth.

Adequate maternal nutrition is important to fetal development and a diet low in saturated fat and cholesterol may help reduce the risk of a preterm delivery.[18]

Factors related to pregnancy history that have been shown to increase the risk of preterm birth include:

  • prior preterm delivery (OR = 2.79)
  • prior induced abortion (OR = 1.6)
  • antepartum hemorrhage / vaginal bleeding during labor
  • prior miscarriage[9]


Multiple pregnancies (twins, triplets, etc.) are another significant factor in preterm birth. The March of Dimes Multicenter Prematurity and Prevention Study found that 54% of twins were delivered preterm vs. 9.6% of singleton births.[19]

Women who have tried to conceive for more than a year before getting pregnant are at a higher risk for premature birth. A recent study done by Dr. Olga Basso of the University of Aarhus in Denmark and Dr. Donna Baird of the U.S. National Institute of Environmental Health Sciences suggests that women who had difficulty conceiving were about 40 percent higher risk of preterm birth than those who had conceived easily.

Finally, the use of tobacco and alcohol during pregnancy also increases the chance of preterm delivery. Tobacco is the most commonly abused drug during pregnancy and also contributes significantly to low birth weight delivery.[20][21]

Prevention of preterm birth

Recent research has identified possible methods to prevent preterm birth, pre-eclampsia/eclampsia, premature rupture of membranes, and preterm labor.

These include self-care methods to reduce infections, nutritional and psychological interventions, and the control of preterm birth risk factors (e.g. working long hours while standing on feet, carbon monoxide exposure, domestic abuse, and other factors). Injection with a form of progesterone (17 alpha-hydroxyprogesterone caproate) although the safety of this treatment for the fetus has been questioned by the FDA and its expert panel due to an associated increase in miscarriage and fetal death[22], the use of vaginal progesterone[13][14] ,taking fish oil supplements, and self-monitoring vaginal PH followed by yogurt treatment or Clindamycin treatment if the PH was too high all seem to be effective at reducing the risk of preterm birth.[23][24] This research is quite new; however, doctors using these newer strategies have obtained preterm birth rates as low as 1 to 2%, compared to the 11 to 16% currently in the US. [citation needed]

Although short term use of folic acid may not have an effect, genetic variation in folate metabolism affects prematurity, and a recent report suggests that usage by mothers for more than a year before birth can reduce premature birth by 50 to 70 percent.[25][26]

Symptoms and indications

The symptoms of an imminent premature birth include:

  • Four or more uterine contractions in one hour, before 37 weeks' gestation.
  • A watery discharge from the vagina, which may indicate premature rupture of the membranes surrounding the baby.
  • Pressure in the pelvis or the sensation that the baby has "dropped".
  • Menstrual cramps or abdominal pain.
  • Pain or rhythmic tightening in lower abdomen or back.
  • Vaginal spotting or bleeding.

Maternal treatments

There are two tactics that can be used to deal with a potential premature birth: delay the arrival of birth as much as possible, or prepare the prospectively premature fetus for arrival. Both of these tactics may be used simultaneously.

Delaying the premature birth from occurring is typically the most favored option. This gives the fetus or fetuses as much time as possible to mature in the womb. There are a number of techniques that can be used to try to accomplish this. The first resort is usually complete bed rest. Maintaining a horizontal position reduces pressure on the cervix, which may allow it to stay lengthened longer, and avoiding unnecessary movement may reduce uterine irritation, which can lead to contractions. Likewise, proper nutrition and especially hydration are important: dehydration can lead to premature uterine contractions. In a hospital setting, a drug-free IV drip may be used to try to stop premature labor simply by improving the mother's hydration. Lastly, there are anti-contraction medications (tocolytics), such as ritodrine, fenoterol, nifedipine and atosiban, although these do not appear to have more than a short-term effect on delaying delivery.

Premature birth can not always be prevented. Severely premature infants may have underdeveloped lungs, because they are not yet producing their own surfactant. This can lead directly to Respiratory Distress Syndrome, also called hyaline membrane disease, in the neonate. To try to reduce the risk of this outcome, pregnant mothers with threatened premature delivery prior to 34 weeks are often administered at least one course of glucocorticoids, a steroid that crosses the placental barrier and stimulates growth in the lungs of the fetus. Typical glucocorticoids that would be administered in this context are betamethasone or dexamethasone, often when the fetus has reached viability at 23 weeks. In cases where premature birth is imminent, a second "rescue" course of steroids may be administered 12 to 24 hours before the anticipated birth. There is no research consensus on the efficacy and side-effects of a second course of steroids, but the consequences of RDS are so severe that a second course is often viewed as worth the risk.

Research reported at the 2008 conference of the Society for Maternal-Fetal Medicine suggests that administration of magnesium sulfate (Epsom salt) to women just before premature birth can cut the rate of cerebral palsy in half. While the compound is cheap and safe, it may make mothers and infants groggy, and details are pending scientific publication.[25]

Newborn complications

Premature infants show physical signs of their prematurity and may develop other problems as well. These include, but are not limited to, the following:

Neurologic

Cardiovascular

Respiratory

Gastrointestinal / metabolic

Hematologic

Infectious


The earliest gestational age at which the infant has at least a 50% chance of survival is referred to as the limit of viability. As NICU care has improved over the last 40 years, viability has reduced to approximately 24 weeks,[27][28] although rare survivors have been documented as early as 21 weeks.[6] Though this date is controversial as gestation in this case was measured from the date of conception rather than the date of her mother's last menstrual period gestation appear 2 weeks less than if calculated by the more common method[29]. As risk of brain damage and developmental delay is significant at that threshold even if the infant survives, there are ethical controversies over the aggressiveness of the care rendered to such infants. The limit of viability has also become a factor in the abortion debate.

Some of the complications related to prematurity are not apparent until years after the birth. For example, children who were born prematurely (especially if born less than 1,500 grams) have a higher likelihood of having behavioral problems, delays in motor development, and difficulties in school. Specifically these problems can be described as being within the executive domain and have been speculated to arise due to decreased myelinization of the frontal lobes.[30] Throughout life they are more likely to require services provided by physical therapists, occupational therapists, or speech therapists.

Treatment measures for a premature infant

The required care for premature infants differs greatly depending on the child's gestational age, birth weight, and overall maturity. Measures common among extremely premature infants include:

  • Placing the infant in a warmer or isolette. Premature infants are easily susceptible to cold-stress or hypothermia and infection, and preventing these is a key priority.
  • Infants under 32 weeks typically do not produce enough surfactant in their lungs to enable them to breathe on their own. In these cases, surfactant will be administered to assist them.
  • A breathing tube may be inserted in the infant's trachea, and a ventilator and supplemental oxygen may be used.
  • Adequate nutrition, via a feeding tube or, in extremely premature infants, intravenously. If a feeding tube is used, expressed breast milk from the mother or a breastmilk bank can be used, which lowers the risk of infections such as necrotizing enterocolitis.

Records

James Elgin Gill (born on 20 May 1987 in Ottawa, Canada) was the earliest premature baby in the world. He was 128 days premature (21 weeks and 5 days gestation) and weighed 1 lb. 6 oz. (624 g). He survived and is quite healthy.[31][32]

Amillia Taylor is also often cited as the most-premature baby.[33] She was born on 24 October 2006 in Miami, Florida, at 21 weeks and 6 days gestation.[34] Though this report has created some confusion her gestation was measured from the date of conception (through IVF) rather than the date of her mother's last menstrual period making her appear 2 weeks younger than if gestation was calculated by the more common method[35]. At birth she was 9 inches (23 cm) long and weighed 10 ounces (283 grams).[33] She suffered digestive and respiratory problems, together with a brain hemorrhage. She was discharged from the Baptist Children's Hospital on 20 February 2007.[33]

The record for the smallest premature baby to survive was held for some time by Madeline Mann, who was born at 26 weeks weighing 9.9 oz (280 g) and 9.5 inches (24 cm) long.[36] This record was broken in September 2004 by Rumaisa Rahman, who was born in the same hospital[37] at 25 weeks gestation. At birth she was eight inches (20 cm) long and weighed 244 grams (8.6 ounces). Her twin sister was also a small baby, weighing 563 grams (1 pound 4 ounces) at birth. During pregnancy their mother had suffered from pre-eclampsia, which causes dangerously high blood pressure putting the baby into distress and leading to birth by caesarean section. The larger twin left the hospital at the end of December, while the smaller remained there until 10 February, 2005 by which time her weight had increased to 1.18 kg (2 pounds 10 ounces).[38] Generally healthy, the twins had to undergo laser eye surgery to correct visual problems, a common occurrence among premature babies.

Historical figures who were born prematurely include Johannes Kepler (born in 1571 at 7 months gestation), Isaac Newton (born in 1643, small enough to fit into a quart mug, according to his mother), Winston Churchill (born in 1874 at 7 months gestation), and Anna Pavlova (born in 1885 at 7 months gestation).[39]

See also

References

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  2. ^ WHO | Data and statistics
  3. ^ Child Health Research Project Special Report. "Reducing Perinatal and Neonatal Mortality." Meeting Report, vol. 3, no 1. Baltimore, Maryland, May 10–12, 1999.
  4. ^ Mathew TJ and MacDorman MF. "Infant Mortality Statistics from the 2003 Period Linked Birth/Infant Death Data Set." National Vital Statistics Reports, vol. 54, no 16. Hyattsville, Maryland: National Center for Health Statistics, 2006.
  5. ^ March of Dimes. The Growing Problem of Prematurity. October 2006.
  6. ^ The Age Depression Linked to Premature Birth. May 2004.
  7. ^ Mayo Clinic. Premature Birth. 6 November 2006.
  8. ^ Burton, Edward M. and Brody, Alan S.,Essentials of Pediatric Radiology, Thieme, ISBN 0-865-77802-7
  9. ^ a b c Goldenberg RL, Iams JD, Mercer BM; et al. (1998). "The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network". Am J Public Health. 88 (2): 233–8. PMID 9491013. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  10. ^ Bánhidy F, Acs N, Puhó EH, Czeizel AE (2007). "Pregnancy complications and birth outcomes of pregnant women with urinary tract infections and related drug treatments". Scand. J. Infect. Dis. 39 (5): 390–7. doi:10.1080/00365540601087566. PMID 17464860. {{cite journal}}: Cite has empty unknown parameter: |1= (help); Text "1B69BA326FFE69C3F0A8F227DF8201D0" ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ a b Martius JA, Steck T, Oehler MK, Wulf KH (1998). "Risk factors associated with preterm (<37+0 weeks) and early preterm birth (<32+0 weeks): univariate and multivariate analysis of 106 345 singleton births from the 1994 statewide perinatal survey of Bavaria". Eur. J. Obstet. Gynecol. Reprod. Biol. 80 (2): 183–9. PMID 9846665.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ To MS, Skentou CA, Royston P, Yu CKH, Nicolaides KH. Prediction of patient-specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: a population-based prospective study. Ultra Obstet Gynecol 2006; 27: 362–367.
  13. ^ a b Fonseca et al. Progesterone and the risk of preterm birth among women with a short cervix. NEJM 2007; vol 357, no 5, pg 462–469.
  14. ^ a b Romero R. Prevention of sponatneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. Ultrasound Obstet Gynecol 2007; 30: 675–686. http://www3.interscience.wiley.com/journal/99020267/home free download
  15. ^ Rosenberg TJ, Garbers S, Lipkind H, Chiasson MA (2005). "Maternal obesity and diabetes as risk factors for adverse pregnancy outcomes: differences among 4 racial/ethnic groups". Am J Public Health. 95 (9): 1545–51. doi:10.2105/AJPH.2005.065680. PMID 16118366.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Dole N, Savitz DA, Hertz-Picciotto I, Siega-Riz AM, McMahon MJ, Buekens P (2003). "Maternal stress and preterm birth". Am. J. Epidemiol. 157 (1): 14–24. doi:10.1093/aje/kwf176. PMID 12505886.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Jeffcoat, Marjorie K., Nico C. Geurs, Michael S. Reddy, Suzanne P. Cliver, Robert L. Goldenberg, and John C. Hauth. "Periodontal Infection and Preterm Birth." The Journal of the American Dental Association 132 (2001): 875–880. 25 April 2007 [1].
  18. ^ "Cholesterol Lowering Diet for Pregnant Women May Help Prevent Preterm Birth." BMJ: British Medical Journal 331 (2005): 1093. 1 May 2007 [2].
  19. ^ Gardner MO, Goldenberg RL, Cliver SP, Tucker JM, Nelson KG, Copper RL (1995). "The origin and outcome of preterm twin pregnancies". Obstet Gynecol. 85 (4): 553–7. doi:10.1016/0029-7844(94)00455-M. PMID 7898832.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ Shiono, Patricia H., Mark A. Klebanoff, Robert P. Nugent, Mary F. Cotch, Diana G. Wilkins, Douglas E. Rollins, Christopher J. Carey, and Richard E. Behrman. "Fetus-Placenta-Newborn: the Impact of Cocaine and Marijuana Use on Low Birth Weight and Preterm Birth: a Multicenter Study." American Journal of Obsetrics and Gynecology 172 (1995): 19–27. 1 May 2007 [3].
  21. ^ Parazzini, F, L. Chatenoud, M. Surace, L. Tozzi, B. Salerio, G. Bettoni, and G. Benzi. "Moderate Alcohol Drinking and Risk of Preterm Birth." European Journal of Clinical Nutrition 57 (2003): 1345. 1 May 2007 [4].
  22. ^ Advisory Committees: CDER 2006 Meeting Documents
  23. ^ Lamont RF and Jaggat AN. Emerging drug therapies for preventing spontaneous preterm labor and preterm birth. Expert Opin Investig Drugs. 2007 16:337–45. PMID 17302528
  24. ^ Hoyme UB and Saling E. Efficient prematurity prevention is possible by pH-self measurement and immediate therapy of threatening ascending infection. Eur J Obstet Gynecol Reprod Biol. 2004 115:148–53. PMID 15262346
  25. ^ a b "Study: Giving moms magnesium sulfate cuts risk of cerebral palsy in extreme premature babies".
  26. ^ PMID 17074544
  27. ^ Kaempf JW, Tomlinson M, Arduza C; et al. (2006). "Medical staff guidelines for periviability pregnancy counseling and medical treatment of extremely premature infants". Pediatrics. 117 (1): 22–9. doi:10.1542/peds.2004–2547. PMID 16396856. {{cite journal}}: Check |doi= value (help); Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) — in particular see TABLE 1 Survival and Neurologic Disability Rates Among Extremely Premature Infants
  28. ^ Morgan MA, Goldenberg RL, Schulkin J (2008). "Obstetrician-gynecologists' practices regarding preterm birth at the limit of viability". J. Matern. Fetal. Neonatal. Med. 21 (2): 115–21. doi:10.1080/14767050701866971. PMID 18240080.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Template:Http://abcnews.go.com/Health/story?id=2890242&page=1
  30. ^ Böhm, Katz-Salamon, Smedler, Lagercrantz & Forssberg: "Developmental Risks and Protective Factors for Influencing cognitive outcome at 5,5 years of age in very-low-birthweight children". Developmental Medicine & Child Neurology 2002, 44: 508–516.
  31. ^ "Powell's Books — Guinness World Records 2004 (Guinness Book of Records) by". Retrieved 2007-11-28.
  32. ^ "Miracle child". Retrieved 2007-11-28.
  33. ^ a b c "Most-premature baby allowed home". BBC News. 2007-02-21. Retrieved 2007-05-05. {{cite news}}: Check date values in: |date= (help)
  34. ^ "trithuc.thanhnienkhcn.org.vn". Retrieved 2007-11-28.
  35. ^ Template:Http://abcnews.go.com/Health/story?id=2890242&page=1
  36. ^ "The Hindu : A little miracle called Madeline". Retrieved 2007-11-28.
  37. ^ "World's Smallest Baby Goes Home, Cellphone-Sized Baby Is Discharged From Hospital — CBS News". Retrieved 2007-11-28.
  38. ^ CBS News. 8 February 2005. World's Smallest Baby Goes Home
  39. ^ Raju, T. N. K. (1980). Some Famous "High Risk" Newborn Babies. In Historical Review and Recent Advances in Neonatal and Perinatal Medicine. Retrieved June 23, 2006.
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