Table 2.

Neonatal key terms and concept definitions.

Term/synonyms	Concept definition	Prioritization
Events of delivery
Live Birth^* S: Live born	Delivery of an infant, regardless of maturity or birth weight, as determined by the presence of a heartbeat or spontaneous respirations or spontaneous movement	Enabling term or outcome
Stillbirth^* S: Stillborn Fetal Demise/Death Deadborn	Delivery of a dead fetus after 22 weeks of gestation (WHO)	Priority outcome
	Categories:
	- Early Stillbirth Delivery ≥22 weeks and/or >500g
	- Late Stillbirth Delivery ≥28 weeks and/or >1000g
	Other commonly reported subgroups:
	- Antepartum or during pregnancy or “macerated”
	- Intrapartum, defined as no signs of life at delivery and more than 500 g or >22 weeks of gestation, with intact skin and no signs of disintegration in utero. The death is assumed to have occurred in the 12 h before delivery and to be more likely due to an intrapartum event. Excludes babies with severe congenital anomalies
Perinatal death^*	Death of fetus at or after 22 weeks of gestation and/or neonate up to 1 week (7 days) after birth	Priority outcome
Neonatal death^*	Death of a live newborn at any time from birth to 28 days of life, regardless of gestational age.	Priority outcome
	Subgroups:
	Very early neonatal death: <24 h
	Early neonatal death: birth to <7 days
	Late neonatal death: 7 to <28 days
Infant death^*	Death of a live born occurring from birth until 12 months of age	Priority outcome
Infant death^*	Subgroup: post-neonatal death: occurs between 28 days and 1 year of life	Priority outcome
Term birth^*	Birth at ≥37 weeks to <42 weeks of gestation	Enabling term or outcome
Preterm birth^*	Birth before 37 weeks of gestation are completed	Priority outcome
	Subgroups: (WHO)
	Moderate to late Preterm: 32 to <37 weeks
	Very Preterm: 28 to <32 weeks
	Extreme Preterm: <28 weeks
Early term birth^*	Birth at 37 to <39 weeks of gestation	Outcome
Post-term birth^* S: Post-mature birth	Birth on or after 42 weeks of gestation	Outcome
Physical examination and anthropometric measurements
Low Apgar Scores^*	Score of less than 7 on a 10 point Apgar scale after 5 min	Outcome
Low Birth Weight^*	Birth weight below the normal birth weight range of 2500 to 3999 g	Priority outcome
	Subgroups:
	Low birth weight (LBW): <2500 g
	Very low birth weight (VLBW): <1500 g
	Extremely low birth weight (ELBW):<1000 g
High birth weight^* S: Macrosomia	Birth weight ≥4000 g	Outcome
Small for Gestational Age (SGA)^* S: IUGR = intrauterine growth restriction	Birth weight <10% for infants of same gestational age and gender in same population	Priority outcome
Large for Gestational Age (LGA)^*	Birth weight >90% for infants of same gestational age in same population	Outcome
Birth length^*	Crown-foot length in cm assessed in relation to gestational age	Enabling term
Microcephaly^*	Head circumference >2 Standard deviations below mean for gestational age, gender and ethnic origin	Outcome
Macrocephaly^*	Head circumference >2 standard deviations above mean for gestational age, gender and ethnic origin	Outcome
Congenital anomalies^* S: Birth defects Malformations	Abnormalities of body structure or function that are present at birth and are of prenatal origin. (WHO)	Priority outcome
	MAJOR ANOMALIES
	Those that require surgical/medical treatment, have serious adverse effects on health or development (functional), or have significant cosmetic impact.
	MINOR ANOMALIES
	Those that do not in themselves have serious medical, functional or cosmetic consequences for the child. Includes those found in association with major anomalies
Neonatal conditions classified by organ system
Systemic conditions
Asphyxia^*	Insufficient oxygen supply to organs at birth resulting from inadequate ventilation or perfusion	Priority outcome
Fever^*	Elevated body temperature at or above 38 °C measured at least once (BC)^a	Outcome
Hypothermia	Decreased body temperature below 36 °C	Taskforce key term
Infection^*	Infection regardless if acquired in utero, intrapartum or in neonatal period	Priority outcome
	Congenital infection: Acquired in utero at any time of gestation and prior to delivery
	Key Event: Infection caused by organism for which mother received vaccination during pregnancy (vaccine associated or vaccine failure)
Sepsis	Infection associated with cardiovascular collapse and systemic, multiorgan involvement.	Taskforce key term
	Neonatal sepsis: Sepsis diagnosed in the first 28 days of life.
	Accepted Categories:
	(WHO)
	Early onset: <7 days of age
	Late onset: 7–90 days of age
	(NCS) Early onset: <72 h of life
	Late onset: ≥72 h of life
Sudden infant death syndrome^* S: SIDS, cot death	Sudden death of any child under 12 months of age which remains unexplained after excluding other causes of death (BC)^b	Priority outcome
Failure to thrive or growth deficiency^*	Inability to maintain expected growth rate over time, evaluated by plotting individual weight gain and growth on standard growth charts for the population	Suggested outcome and taskforce key term
Respiratory tract
Respiratory distress^*	Increase in respiratory rate above normal range for age and labored breathing (nasal flaring, grunting, retractions, pallor and cyanosis or hypoxemia). May be transient or persistent	Suggested outcome
Transient tachypnea of newborn S: TTN	Respiratory distress beginning shortly after birth and usually resolving over 24–48 h or within 3 days of delivery.	Taskforce key term
Transient tachypnea of newborn S: TTN	Usually associated with retained lung fluid after delivery AND Cesarean section delivery with or without labor in term or preterm infants usually >35 weeks of gestation	Taskforce key term
Meconium Aspiration syndrome S: MAS Aspiration pneumonia	Respiratory distress syndrome associated with presence of meconium stained amniotic fluid in the lungs during or before delivery.	Taskforce key term
Meconium Aspiration syndrome S: MAS Aspiration pneumonia	Usually associated with fetal distress prior to and at the time of delivery in term or post-term infants AND visual inspection of trachea and larger airways by endotracheal intubation and suctioning to determine the presence of meconium stained amniotic fluid	Taskforce key term
Respiratory distress syndrome S: RDS Hyaline membrane disease Surfactant deficiency syndrome	A respiratory syndrome in premature infants caused by developmental insufficiency of surfactant production and structural immaturity in the lungs. Begins shortly after birth and is manifest by respiratory distress	Taskforce key term
Persistent pulmonary hypertension of the newborn S: PPHN Persistent fetal circulation	Persistence of fetal circulatory pattern of right to left shunting through the patent ductus arteriosus and foramen ovale after birth due to excessively high pulmonary vascular resistance. Begins shortly after birth, usually within the first 12 h of life, and is manifest by respiratory distress AND hypoxemia that is unresponsive to 100% oxygen and out of proportion with findings in chest X-ray. Usually occurs in term infants	Taskforce key term
Apnea^*	Cessation of breathing for 15 (or 20) s or more, or a shorter respiratory pause associated with bradycardia, cyanosis or hypoxemia, pallor, and/or hypotonia. Should be distinguished from periodic breathing	Suggested outcome
Pneumonia	An inflammatory condition of the lung affecting primarily the alveoli. It is usually caused by infection with viruses or bacteria.	Taskforce key term
Pneumonia	Key event: Infection caused by organism for which mother received vaccination during pregnancy	Taskforce key term
Chronic lung disease S: Bronchopulmonary dysplasia (BPD)	A chronic lung disorder characterized by inflammation and scarring in the lungs that is most common among infants who were born prematurely and result in need for supplemental oxygen	Taskforce key term
Neurologic/neuromuscular
Neonatal Hypoxia^* S: Neonatal Asphyxia	Decreased arterial concentration of oxygen and insufficient blood flow to cells or organs to maintain their normal function, particularly the central nervous system.	Taskforce key Term and Suggested outcome
	Related terms:
	Asphyxia = insufficient oxygen supply to organs due to poor ventilation or poor perfusion
	Anoxia = complete lack of oxygen
	Hypoxia = decreased arterial concentration of oxygen
	Ischemia = insufficient blood flow to maintain normal organ function
Neonatal Encephalopathy^* S: Birth Asphyxia Perinatal Asphyxia	Injury to the central nervous system that occurs when there is insufficient delivery of oxygen or blood to all or part of the brain (NCS)	Priority outcome and Taskforce key term
	OR
	A disturbance of neurological function manifested by difficulty initiation and maintaining respiration, depression of tone and reflexes, abnormal level of consciousness and often seizures.
	1. Due to intrapartum hypoxic insult
	2. Due to another cause
	May be mild, moderate or severe.
	Assessed by clinical and laboratory findings including: 5 min Apgar score of 0–3; Respiratory distress and Acidosis (pH < 7.0); Altered tone, depressed level of consciousness, seizures; Multiorgan involvement; Abnormal CNS imaging or EEG. May result in neonatal death or permanent damage to the brain and other organs. May be associated with perinatal events, rarely to prenatal events
Hypoxic Ischemic Encephalopathy^* S: HIE	A syndrome of abnormal neurological behavior in the neonate, which is frequently associated with multi-system dysfunction and follows severe injury before or during delivery, associated with hypoxic and/or ischemic event.	Priority outcome and Taskforce key term
	May be mild, moderate or severe.
	Comment: The term Neonatal Encephalopathy, specifying if it is associated with intrapartum event, is preferred
Lethargy	Reduced responsiveness to environmental stimuli	Taskforce key term
Irritability^*	Abnormal responsiveness to stimuli or physiologic arousal, may be in response to pain, fright, a drug, emotional situation or a medical condition (CTCAE)	Suggested outcome
Seizure^* S: Convulsion	Witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic–clonic, or atonic motor manifestations (BC)^c	Suggested outcome
Hypotonia/hypertonia	Decreased or increased muscular tone for gestational and post-natal age	Taskforce key term
Hyporreflexia/hyperreflexia	Decreased or increased reflexes for gestational and post-natal age	Taskforce key term
Meningitis	Inflammatory process of the meninges (BC)^d	Taskforce key term
Meningoencephalitis	Inflammatory process of the meninges and brain parenchyma (BC)^e	Taskforce key term
Intracranial intraventricular hemorrhage S: IVH	Bleeding in the ventricles or brain parenchyma	Taskforce key term
Intracranial intraventricular hemorrhage S: IVH	Associated with prematurity or other factors such as trauma, RDS, hypoxia–ischaemia, hypo- or hypertension, other maternal and fetal factors.	Taskforce key term
Periventricular leucomalacia S: PVL	Decreased perfusion, periventricular hemorrhage and/or necrosis in the periventricular white matter and/or white matter, Associated with prematurity and IVH, hypoxia-ischemia, other maternal and fetal factors	Taskforce key term
Sleeping issues^*	Disturbance in sleep pattern	Suggested outcome
Neurodevelopmental disability^*	Alteration in progression or regression of normal development of motor, speech or cognitive skills as expected for gestational and post-natal age	Suggested outcome
Neurodevelopmental disability^*	Assessed by medical history, physical examination, and standard screening and assessment tools appropriate for age. Serial assessment required due to variability in individual acquisition of skills. Assessment at or beyond 1 year of age more likely to represent true disability	Suggested outcome
Cardiovascular
Tachycardia/Bradycardia^*	Heart rate above or below normal range for age and gestational age	Suggested enabling term
Hypertension/Hypotension	Blood pressure above or below normal range for age, gestational age, gender and length and height	Taskforce key term
Heart failure	Cardiac dysfunction resulting in symptoms	Taskforce key term
Hematologic
Bleeding^*	Loss of blood from any site or etiology	Suggested outcome
Bleeding^*	Assessed by Evidence of bleeding AND symptoms that may include tachycardia, hypotension, diaphoresis, lethargy, pallor, cyanosis, shock AND Anemia (low hemoglobin or hematocrit)	Suggested outcome
Anemia^*	Hematocrit or hemoglobin concentration below the lower limit of normal range for gestational age and post-natal age	Suggested outcome
Polycythemia	Hematocrit or hemoglobin concentration above the upper limit of normal range for gestational age and post-natal age	Taskforce key term
Thrombocytopenia^*	Platelet count below the lower limit of normal range for gestational age and post-natal age (BC)^f	Suggested outcome
Leukopenia	Decreased white blood cell count below lower limit of normal range for gestational and post-natal age	Taskforce key term
Leukocytosis^*	Increased white blood cell count above upper limit of normal range for gestational and post-natal age	Suggested outcome
Coagulopathy S: DIC Disseminated intravascular coagulation	Bleeding and/or clotting disorder associated with abnormal activation of coagulation pathways	Taskforce key term
Gastrointestinal
Difficulty feeding^*	Poor suck and/or inability to maintain adequate oral intake for age	Suggested outcome
Vomiting	Reflexive act of ejecting stomach contents through the mouth	Taskforce key term
Diarrhea	Increase in frequency and/or change in consistency (liquid) of stools for age (BC)^g	Taskforce key term
Necrotizing enterocolitis	Disease of the gastrointestinal tract characterized by mucosal or transmural necrosis of the intestine.	Taskforce key term
Jaundice/Hyperbilirubinemia^*	Elevation of Total and/or Direct–Indirect bilirubin for gestational and post-natal age Subgroups:	Suggested outcome
	Physiologic hyperbilirubinemia
	Neonatal hyperbilirubinemia
	Direct/Conjugated hyperbilirubinemia
	Indirect/Unconjugated hyperbilirubinemia
	Breastfeeding Jaundice
Hepatic dysfunction	Elevation of liver enzymes and/or coagulopathy	Taskforce key term
Metabolic
Hypoglycemia	Low serum glucose concentration (mg/dL) below lower limit of normal for gestational and post-natal age	Taskforce key term
Hypocalcemia/Hypercalcemia	Concentration of serum (mg/dL) or ionized Calcium below or above the lower and upper limits of normal for gestational and post-natal age	Taskforce key term
Hypomagnesemia/Hypermagnesemia	Concentration of serum (meq/L) magnesium below or above the lower and upper limits of normal for gestational and post-natal age	Taskforce key term
Renal
Renal insufficiency	Decreased urinary output and/or elevation of serum creatinine above upper limit of normal for gestational and post-natal age	Taskforce key term
Renal failure	Persistent oliguria or anuria with decreased creatinine clearance for gestational and post-natal age	Taskforce key term
Electrolyte anomalies (Na, K)	Concentration of serum (meq/L) sodium or potassium below or above the lower and upper limits of normal for gestational and post-natal age	Taskforce key term
Other
Birth trauma or injury	Neonatal injury associated with delivery	Taskforce key term
Birth trauma or injury	Assessed by physical exam AND birth history	Taskforce key term
Allergic conditions^*	Infant allergic disorders	Suggested outcome
Autoimmune disorders^*	Maternal and infant autoimmune disorders	Suggested outcome
Infant Immunity^*	Effect of maternal antibodies on infant responses to active vaccination and/or natural infection Effect of maternal antibodies on infant reactogenicity after active vaccination	Suggested outcome
Gender specific events^*	Infant events related to gender	Suggested outcome

Sources of Accepted Definitions: WHO: World Health Organization; BC: Brighton Collaboration; NCS: National Children’s Study; CTCAE: Common Terminology Criteria for Adverse Events (National Institutes of Health); NICHD: National Institute of Child Health and Human Development.

BC-WHO Consultation consensus term.

See Brighton definition: Michael Marcy, S., et al., Fever as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation. Vaccine, 2004. 22(5–6): p. 551–6.

See Brighton Definition: Jorch, G., et al., Unexplained sudden death, including sudden infant death syndrome (SIDS), in the first and second years of life: case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine, 2007. 25(31): p. 5707–16.

See Brighton definition: Bonhoeffer, J., et al., Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation. Vaccine, 2004. 22(5–6): p. 557–62.

See Brighton definition: Tapiainen, T., et al., Aseptic meningitis: case definition and guidelines for collection, analysis and presentation of immunization safety data. Vaccine, 2007. 25(31): p. 5793–802.

See Brighton definition: Sejvar, J.J., et al., Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine, 2007. 25(31): p. 5771–92.

See Brighton definition: Wise, R.P., et al., Thrombocytopenia: case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine, 2007. 25(31): p. 5717–24.

See Brighton definition: idudu, J., et al., Diarrhea: case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine, 2010. 29(5): p. 1053–71.