AUTHOR AND EDITOR INFORMATION

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• Treatment
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• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

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• Multimedia
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Background

Prematurity refers to the broad category of neonates born at less than 37 weeks' gestational age (GA). Although the estimated date of confinement (EDC) is 40 weeks' GA, the World Health Organization broadened the range of full term to include 37-42 weeks' GA.

Premature newborns have many physiologic challenges when adapting to the extrauterine environment. Most articles in the neonatology section discuss in detail the most serious of these problems. Serious morbidities occur in extremely low-birth-weight (LBW) infants. (Refer to Extremely Low Birth Weight Infant, Acute Respiratory Distress Syndrome, Bronchopulmonary Dysplasia, Periventricular Hemorrhage-Intraventricular Hemorrhage.) The near-term neonate (34-36 weeks' GA) has issues of prematurity that include feeding immaturity, temperature instability, and prolonged jaundice. This article provides a general overview of the premature infant.

Pathophysiology

Before birth, the placenta serves 3 major roles for the fetus: provision of all the nutrients for growth, elimination of fetal waste products, and synthesis of hormones that promote fetal growth.

With the exception of most electrolytes, the maternal circulation contains more substrate (eg, blood glucose) than the fetal circulation. In addition, the placenta is metabolically active and consumes glucose. Waste products of fetal metabolism (eg, heat, urea, bilirubin, carbon dioxide) are transferred across the placenta and eliminated by the mother's excretory organs (ie, liver, lung, kidneys, skin).

In addition, the placenta acts as a barrier to infection through mucosal macrophages and by allowing transfer of maternal immunoglobulins (Igs, eg, IgG) to the fetus beginning at 32-34 weeks of gestation. Placental dysfunction is involved in the transfer of IgG. Antibacterial activity of the amniotic fluid improves as GA advances.

Each of the immature organs of a premature infant has functional limitations. The tasks of caregivers in neonatal intensive care units (NICUs) are to recognize and monitor the needs of each infant and to provide appropriate support until functional maturity can be achieved.

Frequency

United States

In the general population, 12% of infants are born prematurely.

International

No reliable numbers are available, as different countries use different definitions of birth (eg, survival after birth, survival after 1 month).

Mortality/Morbidity

The mortality rate is high in developing countries, especially those of sub-Saharan Africa. The perinatal mortality rate is 70 deaths per 1000 births; the neonatal mortality rate is 45 deaths per 1000 live births. Preterm birth is the strongest independent predictor of mortality in the United States. Preterm delivery accounts for 75-80% of all neonatal morbidity and mortality.

Since the early 1960s, survival rates of premature infants substantially increased because of technologic advances. From 1989-1990, infants with birth weights <751 g had a survival rate of 39% (range among centers, 23-48%). In 1992, the US Food and Drug Administration (FDA) approved exogenous surfactant therapy for respiratory distress syndrome (RDS), leading to a considerable improvement in survival rates. Since the FDA approved the use of surfactant and since the subsequent introduction of a number of natural surfactants, the mortality rate attributed to surfactant deficiency has been markedly reduced. (See Acute Respiratory Distress Syndrome.)

Data from the Vermont Oxford Network in 1994-1996 indicated that the survival rate of infants born weighing <1000 g was 74.9%. Survival of infants born weighing less than 1000 g and requiring cardiopulmonary resuscitation in the delivery room was substantially decreased (53.8%) The changes in obstetric and neonatal care in the first half of the decade of 1990s decreased mortality and morbidityfor LBW infants. No additional improvements in mortality and morbidity were observed at the end of the decade.

Obstetric and pediatric personnel must be familiar with their own institutional data in addition to national benchmarks related to GA and mortality rates. These data are essential for proper prenatal counseling of parents and/or caregivers regarding survival and resuscitation plans.

• The 3 primary causes of mortality in infants born with a weight of <1000 g are respiratory failure, infection, and congenital malformation. Infection of the amniotic fluid leading to pneumonia is the major cause of mortality (Barton, 1999). In infants weighing <500 g at birth, immaturity is listed as the only cause of mortality. (See Ethical Issues in Neonatal Care.)
• Women who have an intrauterine infection do not respond to tocolytics. Preterm premature rupture of membranes (PPROM) is associated with 30-40% of premature deliveries. (See Premature Rupture of Membranes.) Mortality of the premature infant increases with coexisting PPROM, but it depends on GA and the expertise of the maternal-fetal monitoring team. Postnatal findings of periventricular leukomalacia (PVL) on cranial sonograms are highly correlated with chorioamnionitis.
• In premature infants with a congenital heart defect (CHD), excluding isolated patent ductus arteriosus, the actuarial survival rate is 51% at 10 years, whereas infants with both CHD and prematurity have substantially worsened outcomes than infants who only have one of these conditions (Dees, 2000). The survival rate improved as the study period (1976-1999) progressed. Congenital anomalies are an independent risk factor for mortality and morbidity in preterm birth.

Race

• Premature infants are born to women of every race. LBW infants are most commonly born to women of low socioeconomic status, African American women, teenage female adolescents, and mothers older than 40 years. Women at highest risk of premature delivery can be assessed by using a scoring system that reviews their socioeconomic status, history, daily habits, and current pregnancy events (Creasy, 1980). About 30% of women with a high-risk score deliver prematurely compared with 2.5% of women with a low-risk score.
• Primarily because of the increased incidence of preterm infants, the overall neonatal mortality rate in African Americans in the United States is 2.3 times that of Caucasians. Improvements in socioeconomic status and perinatal care have not improved the rate of prematurity and infant mortality rate in this population.

Sex

Female sex is associated with increased rates of survival of newborns born at 22-25 weeks' GA.

CLINICAL

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History

• GA dating by using the mother's history can be unreliable because of uncertainty of the dates.
• About 20% of women have an uncertain last menstrual period (LMP).
• GA assessment begins prenatally with obstetric ultrasonography in the first trimester.
• Discovery of many fetal anomalies, unsuspected multiple gestation, location of the placenta, and an accurate dating of the pregnancy are additional major benefits of early ultrasonography.

Physical

Confirmation of GA is based on physical and neurologic characteristics. In 1979, the Dubowitz scoring system for determining GA based on neurologic and physical parameters was revised to include 12 items. The Ballard Scoring System, recently revised again to include extremely LBW infants, remains the main tool clinicians use after delivery to confirm GA by means of physical examination.

• The major parts of the anatomy for physical characteristic markers are ear cartilage (see Images 1-3), sole creases (see Images 4-6), breast tissue (see Images 7-9), and genitalia. This examination should be performed immediately after stabilization and before the expected weight loss occurs on the first day.
• Hittner et al (1997) reported that regression of the vascularity of the lens capsule as an excellent tool to confirm GA of 28-34 weeks' gestation.
• Neurologic criteria include muscle tone of the trunk and extremities and joint mobility.
• Reassessing the neurologic criteria 18-24 hours after birth is best to allow for recovery from maternal medication (eg, magnesium sulfate, analgesics), which may decrease tone and responsiveness.

Causes

Premature delivery can be the result of preterm labor and PPROM or can occur for maternal indications, eg, pregnancy-induced hypertension.

• Chorioamnionitis
• • Amniocentesis that demonstrates bacteria, WBCs, and a low glucose concentration confirms the diagnosis of chorioamnionitis and is an indication for delivery.
  • A decrease in the biophysical score or profile in association with chorioamnionitis is associated with fetal infection.
  • Rates of perinatal mortality, neonatal infection, and RDS increase in the presence of maternal fever and chorioamnionitis.
• Intrauterine growth restriction (10th percentile for birth weight) is significantly associated with perinatal mortality and long-term morbidity.
• Low socioeconomic status: Programs offering additional social support for at-risk pregnant women have not been demonstrated to reduce the numbers of LBW or preterm infants
• Maternal diabetes
• • Pregnancies complicated by diabetes and poor glycemic control are associated with a high incidence of prematurity, macrosomia, malformation, fetal death, and neonatal death.
  • The rate of preterm birth (GA <37 wk) is 20-22% of persons with insulin-dependent diabetes.
  • In women with diabetes diagnosed before pregnancy, the frequency of preeclampsia is increased as the severity of diabetes increases.
• Multiple-gestation pregnancies
• • Women with multiple-gestation pregnancies are at high risk of preterm labor and delivery and account for increasing percentage of preterm births and LBW infants.
  • With advances in assisted reproductive technology, multiple-gestation pregnancies have increased.
  • Preterm birth rate for twins has increased from 40.9% in 1981 to 55% in 1997. Multiple births related to infertility treatment have increased dramatically (Fritz, 2002).
  • Prepregnancy counseling of prospective parents regarding the risks related to multiple gestations is important.
  • Preterm birth ( <35 weeks' GA) occurs in 26% of twins versus in 3% of singletons.
  • Triplet pregnancies are associated with an increased incidence of preterm labor and delivery at a decreased GA and birth weight, as compared with singletons and twins. When the data are controlled for GA, outcomes are similar for singletons, twins, and triplets.
• Maternal age
• • In women aged 13-15 years, the rate of preterm birth is 5.9%. This rate declines to 1.7% in women aged 18-19 years and 1.1% in women aged 20-24 years.
  • The rate of preterm births increases in pregnancies in which the mother is older than 40 years. The scoring system for the risk of preterm delivery uses a criterion of >40 years of age.
• Tobacco use
  • Approximately 15-20% of pregnant women smoke tobacco.
  • Tobacco use is a risk factor for placental abruption and accounts as a factor for 15% of preterm births and 20-30% of LBW infants.

DIFFERENTIALS

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Other Problems to be Considered

Intrauterine growth retardation

WORKUP

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Lab Studies

• Initial laboratory testing is performed to identify issues that, if corrected, improve the patient's outcome.
• Blood tests are performed.
• • CBC findings may reveal anemia or polycythemia that is not clinically apparent.
  • A high or low WBC count and a number of immature neutrophil types also may be found. An abnormal WBC count may suggest subtle infection.
  • A blood type and antibody testing (Coombs test) are performed to detect blood-group incompatibilities between the mother and infant and to identify antibodies against fetal RBCs. Such incompatibilities increase the risk for jaundice and kernicterus.
• Serum electrolytes analysis may be helpful.
• • At birth, most serum electrolyte levels reflect those of the mother.
  • If the mother received magnesium sulfate to inhibit labor, the baby's respiratory effort may be compromised, and the serum magnesium value is elevated.
  • The serum calcium may be low shortly after birth in small preterm babies.
  • Immature renal function, as well as limited bone and tissue reserves, result in the need for intravenous replacement of calcium, sodium, potassium, phosphate, and trace minerals in those infants who are taking nothing by mouth. Infants who can tolerate enteric nutrition receive ample electrolyte and minerals from appropriate preterm formulas and fortified human milk. These issues are more acute with decreasing GA.
  • Frequent laboratory determinations of serum sodium, potassium, and glucose in conjunction with monitoring of daily weight and urine output in extremely LBW infants assists the practitioner in determination of fluid requirements.
• Serum glucose concentrations must be monitored closely because of the risk of hypoglycemia and hyperglycemia in preterm infants. The baby's GA and other medical conditions dictate the frequency of testing (see Hypoglycemia).
• Metabolic screening is done.
• • Every state has a metabolic screening program. All programs include testing of newborn blood spots for a minimum of phenylketonuria, hypothyroidism, and galactosemia. The timing of obtaining the sample varies.
  • In general, false-positive results are most common in preterm babies. Early detection and intervention minimizes the long-term neurologic risk.

Imaging Studies

• Imaging studies are specific to the organ system affected.
• • Chest radiography is performed to assess lung parenchyma in newborns with respiratory distress
  • Cranial ultrasonography is performed to detect occult intracranial hemorrhage in very LBW newborns
• Prematurity itself is not an indication for an imaging study.

Procedures

• Venipuncture: Refer to Lab Studies.
• Lumbar puncture: Perform lumbar puncture in infants with positive blood cultures or in those who have clinical signs of infection (presumed sepsis) and for whom a full course of antibiotic coverage is planned (see Neonatal Sepsis).

TREATMENT

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Medical Care

Stabilization in the delivery room with prompt respiratory and thermal management is crucial to the immediate and long-term outcome of premature infants, particularly extremely premature infants.

Principles of respiratory management are as follows:

• Recruit and maintain adequate lung volume or optimal lung volume. In infants with respiratory distress, this step may be accomplished with early continuous positive airway pressure (CPAP) given nasally, by mask (Neopuff), or by using an endotracheal tube when ventilation and/or surfactant is administered.
• Avoid hyperoxia and hypoxia by immediately attaching a pulse oximeter and keeping the oxygen saturation (SaO₂) between 86% and 93% by using an oxygen blender.
• Prevent barotrauma or volutrauma by using a ventilator that permits measurement of the expired tidal volume and by keeping it 4-7 mL/kg.
• Administer surfactant early (<2 h of age) when indicated and prophylactically in all extremely premature neonates (<29 wk).

Many centers are using early CPAP and a relatively permissive approach to ventilation. Research is needed to provide evidence to support an approach that provides the best outcome.

• Thermoregulation
  • Maintenance of the neutral thermal environment is critical for minimizing stress and optimizing growth of the premature infant. The neutral thermal environment is defined as the environmental temperature in which the neonate maintains a normal temperature and is consuming minimal oxygen for metabolism.
  • Neonates lose heat by 4 means, as follows:
    1. Evaporation: Evaporation is energy consumed by a fluid as it converts from a liquid to gas. This is primarily in the delivery room. Completely drying the infant is of primary importance in prevention of hypothermia. This step can be omitted if other resuscitative measures are taking place.
    2. Conduction: This is direct transfer of heat from a warm body to a cool object by contact (eg, placing an infant on a cold scale).
    3. Convection: This is the loss of heat from the warm air next to the skin to moving air currents (eg, windchill effect). Double-walled isolettes help to reduce convective heat loss.
    4. Radiation: This is the loss of heat that radiates from a warm body to a cool surface (eg, window, outside wall).
  • Preterm infants are relatively unable to compensate for cold stress because of a small amount of subcutaneous tissue (insulation) and decreased brown fat to produce heat.
  • Preterm infants do not shiver. The increased surface area to body mass allows for rapid heat loss, especially from the head.
  • Decreased posturing ability further diminishes their ability to compensate.
  • In extremely LBW infants, immature skin further complicates thermoregulation due to increased evaporative water loss. (See Extremely Low Birth Weight Infant.)
  • Consequences of cold stress are increased metabolism with loss of weight or failure to gain weight and increased use of glucose with depletion of glycogen stores and hypoglycemia.
  • Metabolic acidosis results in a decreased surfactant production and loss of functional alveolar number, which results in hypoxia. The hypoxia causes pulmonary vasoconstriction, and further hypoxia.
  • Increased oxygen consumption results in hypoxia, anaerobic metabolism, and lactic acid production.
  • In the intensive care nursery, radiant warmers may be used to compensate for heat loss. Incubators are more efficient than radiant warmers because the heated environment decreases heat loss due to conduction, convection, and radiation. With radiant warmers, consider using plastic wrap and a humidified environment for extremely LBW infants. New devices function as both an incubator and an overhead warmer to enable access for procedures. In all nurseries, maintain the environmental temperature at >70°F (>21°C).
  • Temperature maintenance is especially critical during neonatal resuscitation, when the same principles apply. (See Neonatal Resuscitation).
• Skin care
  • Premature infants have immature skin, a decreased or absent stratum corneum, decreased cohesiveness between skin layers, increased water fixation, and tissue edema. The immature skin integrity leads to easy injury, transdermal absorption of drugs and other materials in contact with the skin and increased risk for infection.
  • The National Association of Neonatal Nurses (NANN) and the Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) recommended the following areas of newborn skin care, which are based on clinical and laboratory research.
    1. Bathing: Use only water and no soap for infants weighing <1000 g. Decrease the frequency of using cleansers. Only use neutral-pH cleansers.
    2. Disinfectants (eg, povidone-iodine, chlorhexidine): Remove completely these agents after the procedure to decrease transdermal absorption. Isopropyl alcohol use is discouraged because it is relatively ineffective as a disinfectant and is drying to the skin. Alcohol burns, and cracked skin can result.
    3. Adhesives: Minimize their use. Use double-backed silk tape versus tape with strong adhesive properties (Elastoplast). Use hydrogel electrodes. Avoid solvents or bonding agents.
    4. Transepidermal water loss: Place infants born at 30 weeks' GA in a high-humidity (>70%) environment.
    5. Topical solutions: Review ingredients of any topical solution placed on the skin of a preterm infant. Transdermal absorption can occur. Discourage use of solvents for adhesive removal.
    6. Pectin barriers (eg, DuoDERM extra thin, Restore extra thin) are recommended: Anchoring devices (umbilical lines) to pectin barriers results in improved skin integrity.
• Fluid and electrolyte management
• • Preterm infants need intense monitoring of their fluid and electrolytes because of their increased transdermal water loss, immature renal function, and other environmental issues (eg, radiant warming, phototherapy, mechanical ventilation).
  • Expected loss of extracellular water in the first week of life in the term infant is 5% of birth weight, LBW infant is 10% of birth weight, and in the extremely LBW infant is 15-20%. Data curves, which Dancis developed in the 1940s, may be useful in monitoring weight loss in each group of infants.
  • The degree of prematurity and the infant's specific medication problems dictate initial fluid therapy. However, the following general principles apply to all preterm infants:
    • Initial fluids should be a solution of glucose and water. More mature infants can be started at 60-80 mL/kg/day. The most immature infants may need up to 100-150 mL/kg/d. (See Extremely Low Birth Weight Infant.)
    • Environmental aspects of care, eg, radiant warming, phototherapy, and a nonhumidified environment, increase insensible water loss and the need for fluids. Mechanical ventilation, use of double-walled isolettes, and provision of humidity decrease insensible water loss.
    • The glucose infusion rate (GIR) is usually started at 4-6 mg/kg/min. In general, to obtain this rate, a solution of dextrose 10% in water (D10W) should be used initially. The exception is the extremely LBW infant who should initially be given dextrose 5% in water (D5W) to provide the same GIR and to prevent hyperglycemia.
    • Electrolytes should not be added until 24 hours of age, when urine output is adequate. Electrolytes and calcium should be monitored at 12-24 hours of age depending on the degree on prematurity and other medical issues.
    • Basal needs are sodium is 2-3 mEq/kg/d, potassium 1-2 mEq/kg/d, and calcium 600 mg/kg/d (as calcium gluconate). Urinary losses, which may increase in the most immature of infants and in those exposed to diuretics, dictate the need for supplemental sodium.
    • Infants who develop acute tubular necrosis (ATN) should be treated with fluid restriction that equals insensible water loss plus urine output. Additional fluid is administered by closely and frequently monitoring the output and electrolytes during the post-ATN diuretic phase.
    • Hyponatremia and weight gain should be treated with decreasing fluid administration. Monitoring of urinary electrolyte losses is sometimes helpful in replacement therapy.
    • The patient's weight should be followed up every 24 hours. Results of laboratory monitoring and change in weight dictate changes in fluid and electrolyte support.

Consultations

• A developmental specialist might be consulted. The risk of neurodevelopmental problems occurs as GA and birth weight decrease.
• Hearing screening should be performed on all newborns before they are discharged.

Diet

Preterm infants born at <34 weeks of gestation have poor coordination of the suck and swallow reflexes and decreased intestinal motility. Nutrition in the first several days after birth often is provided intravenously. Even the relatively healthy preterm infant may not reach full enteral nutrition until a week or longer after birth.

• Colostrum
• • If available, colostrum is the preferred initial nourishment.
  • Colostrum contains digestible proteins, antibody (secretory immunoglobulin A [IgA]), growth factors, and other components that in the aggregate promote intestinal villous growth and influence the intestinal colonization.
• Mature breast milk
• Mature breast milk replaces transitional milk by 10-12 days after birth.
• The caloric density varies among mothers based in part on the mother's nutritional status.
• For extremely LBW infants, breast milk is often inadequate to sustain growth.
• Most calories are contained in lactose (35%) and fat (50%). In the more preterm infants, lactase activity is low which may contribute to less-than-optimal digestion of lactose and absorption of carbohydrate. This improves with GA.
• Calcium, sodium, potassium, and trace mineral levels are insufficient to meet the needs of the preterm infant. Therefore, minerals, protein, carbohydrates, and lipids often are added to breast milk to support optimal growth in the form of commercially available breast milk fortifiers.
• Approximately 120-150 cal/kg/d are required for growth. Small preterm infants with increased metabolic needs due to complications such as bronchopulmonary dysplasia (BPD) may require up to 180 cal/kg/d to grow.
• Formula
  • Preterm formulas have been developed to address the specific needs and digestive abilities of the preterm infant.
  • The typical formula contains more easily digested glucose polymers (50% of carbohydrates) and medium chain triglycerides that minimize the need for active lipase activity.
  • Although preterm formula contains more calcium and phosphorus than breast milk, osteopenia of prematurity and poorly mineralized primary teeth remain clinically significant problems. Poor early intravenous nutrition and the use of diuretics often exacerbate these problems. Increased sodium compensates for poor renal retention.
  • The formulas contain additional trace minerals and vitamins.

MEDICATION

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Prematurity is not a specific illness. Medications administered to an infant are prescribed for a specific purpose and are discussed in each of the articles mentioned above about specific disease processes.

FOLLOW-UP

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Further Inpatient Care

• Discharge criteria are as follows:
• • The parents and/or caregivers are capable. That is, they demonstrate an ability to meet the needs of the infant.
  • The patient's caloric intake is adequate for growth.
  • The patient has been weaned from supplemental heat.
  • Medical problems are defined and manageable at home.
  • No apnea or bradycardia is present.

Further Outpatient Care

• Developmental assessment and intervention, as appropriate

Transfer

• Primary transfer to a tertiary center
• • Transferring to a center that specializes in care of high-risk mothers and infants improves outcome because of the availability of resources and experience.
  • Transfer can help in addressing neonatal issues of intravenous support and oxygenation and/or mechanical ventilation. It also provides access to pediatric subspecialists.
• Reverse transfer
• • Consider transport and/or insurance costs.
  • Transfer may permit the family to be near the patient and to establish a family support system.
  • Reverse transfer may extend good will to the referring hospital (and forge ties to the regional NICU) and promote continuity with the referral physician for discharge.
  • This may improve the experience of local hospital staff.
  • This may help in decompressing the regional NICU.
  • Reverse transfer may aid in addressing social service concerns.

Prognosis

• Mortality and morbidity are inversely proportional to GA and birth weight.
• Infants with extremely LBW who are born at tertiary care centers have outcomes more favorable than those who are born at level I or II centers and then transferred.

Patient Education

• Discharge teaching of the premature infant includes the following:
• • Basic infant care - Bathing, skin care, taking a temperature
  • Infant feeding - Feeding cues, support of breastfeeding
  • Infant safety - Use of car seats, avoiding exposure to a smoky environment
  • Back to sleep - Strategies to help preterm infants return to sleep
  • Illness prevention (handwashing, avoid crowds, prophylaxis against infection with respiratory syncytial virus (RSV) as indicated, immunization schedule
  • When to call healthcare provider - Poor feeding, signs of illness, change in behavior, respiratory distress
  • Specifics related to chronic conditions - For example, use of a nasal canula and home oxygen therapy

MISCELLANEOUS

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Medical/Legal Pitfalls

• The medical-legal risk primarily is linked to adverse outcome, inappropriate expectations on the part of the family, and poor communication with the family.
• The smallest and most immature infants are at greatest risk of mental retardation and motor delay or disability.

MULTIMEDIA

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Media file 1:  Preterm infant at 28 weeks' gestation. Note the small amount of ear cartilage and/or flattened pinna.
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Media file 2:  Preterm infant at 33 weeks' gestation. Note the increased cartilage, recoil, and outer ridge curving inward.
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Media file 3:  A term infant has well-developed cartilage with instant recoil.
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Media file 4:  Preterm infant at 28 weeks' gestation. Note the flat sole.
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Media file 5:  Preterm infant at 33 weeks' gestation. Note the presence of only an anterior crease.
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Media file 6:  Term gestation. Note the multiple creases.
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Media file 7:  Preterm infant at 28 weeks' gestation. No breast tissue is present, and the areolae are barely visible.
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Media file 8:  Preterm infant at 33 weeks' gestation. The breast tissue is less than 1 cm, and the areolae are raised and/or pigmented.
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REFERENCES

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• Barton L, Hodgman JE, Pavlova Z. Causes of death in the extremely low birth weight infant. Pediatrics. Feb 1999;103(2):446-51. [Medline].
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• Doron MW, Veness-Meehan KA, Margolis LH, et al. Delivery room resuscitation decisions for extremely premature infants. Pediatrics. Sep 1998;102(3 Pt 1):574-82. [Medline].
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• Finer NN, Horbar JD, Carpenter JH. Cardiopulmonary resuscitation in the very low birth weight infant: the Vermont Oxford Network experience. Pediatrics. Sep 1999;104(3 Pt 1):428-34. [Medline].
• Fritz MA. Infertility treatment and the multifetal gestation epidemic: too much of a good thing. Contemporary OB-GYN. 2002;65-90.
• Furdon SA, Lapitsky J, Diven S, Horgan MJ. Effect of standardized approach to the care of the extremely low birthweight infant. J Nurs Care Qual. Aug 1997;11(6):42-51. [Medline].
• Gracey K, Talbot D, Lankford R, Dodge P. Family teaching toolbox. Nasal cannula home oxygen. Adv Neonatal Care. Apr 2003;3(2):99-101. [Medline].
• Groh-Wargo S, Hovasi Cox J. Nutritional Care for High-Risk Newborns. Los Angeles, Calif: Bonus; 3rd ed. 2000.
• Hittner HM, Hirsch NJ, Rudolph AJ. Assessment of gestational age by examination of the anterior vascular capsule of the lens. J Pediatr. Sep 1977;91(3):455-8. [Medline].
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Article Last Updated: Oct 16, 2006