Version May 2024
INTRODUCTION — Periviability, also referred to as borderline viability, is defined as the earliest stage of fetal maturity (ie, between 22 and <26 weeks gestation) when there is a reasonable chance, although perhaps not a high likelihood, of extrauterine survival. Infants born at these gestational ages are at significant risk for death, or survival with chronic medical conditions including permanent disability that often requires complex medical care. As a result, management of these infants is challenging, as decision-making must be based on both clinical and ethical considerations.
This topic will discuss management of periviable infants based on an ethical framework and outcome data. The management of pregnancies at or near the limit of viability is discussed separately. (See "Delivery of the low birth weight singleton cephalic fetus", section on 'Management at/near the limit of viability'.)
DEFINITIONS
Neonatal terminology
●Periviability – Earliest stage of fetal maturity where there is a reasonable chance, although perhaps not a high likelihood, of extrauterine survival. This period is generally between 22 and <26 weeks gestational age (GA). Most infants born at ≥26 weeks GA have a high likelihood of survival, whereas virtually none born at <22 weeks GA survive.
●Extremely preterm (EPT) birth – Birth at a GA <28 weeks.
●Extremely low birth weight (ELBW) – Birth weight <1000 g.
●Neurodevelopmental outcome – This composite term typically refers to the level of cognitive, behavioral, motor, and sensory abilities of surviving infants measured against peers at different time points later in life.
●Neurodevelopmental impairment (NDI) – NDI is defined as the presence of one or more of the following deficits (see "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors"):
•Cognitive delay, based on scores on standardized cognitive tests that are 2 standard deviations (SD) below the mean. As an example, this would correspond to score of 70 or below on the Mental Developmental Index of the Bayley Scales of Infant Development.
•Moderate to severe cerebral palsy (CP), defined as a score of ≥2 on the Gross Motor Function Classification System (GMFCS). (See "Cerebral palsy: Classification and clinical features", section on 'Functional classification systems'.)
•Bilateral hearing deficit/loss, defined as the need for hearing amplification or inability to hear despite amplification.
•Severe visual impairment, defined as visual acuity of 20/200 or less in the better-seeing eye with best conventional correction (definition of legal blindness).
•Behavioral problems such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), or other difficulties with attachment or socialization. (See "Autism spectrum disorder in children and adolescents: Evaluation and diagnosis" and "Attention deficit hyperactivity disorder in adults: Epidemiology, clinical features, assessment, and diagnosis".)
•Psychological problems refer to psychologic conditions such as anxiety, depression, impulse control, and obsessive-compulsive disorder.
Terms related to medical ethics — Principlism is a framework commonly employed for reasoning in medical ethics. It encompasses four guiding principles:
●Autonomy – Literally, "self-rule," with the ability to make decisions for oneself free from controlling interference or limitation of inadequate understanding. In medicine, respecting autonomy means ensuring a patient's right to be informed and participate in medical decision-making, generally including the right to refuse a medical intervention for one's self.
•Parental/caregiver authority – The right of parents and/or legal caregivers to serve as surrogate decision-makers for their infant who cannot make decisions on their own. With this right comes the obligation to act in the child's interests and the limitation that this authority can be overridden should a decision result in direct, unnecessary harm to the child.
●Beneficence – Beneficence is defined as the clinician's obligation to weigh the benefit and burdens of medical treatment and provide care that will be in the best interests of their patient.
●Non-maleficence – Non-maleficence is defined as the clinician's obligation to minimize unnecessary harms or unwanted complications that result from medical treatment.
●Justice – Justice requires that individuals be treated equally unless there is a morally relevant reason not to do so. In medicine, this translates to patients of similar prognoses being treated equally and health resources being used equitably.
ETHICAL FRAMEWORK — Due to the high risk and clinical uncertainty regarding survival and long-term complications associated with periviable birth, management must take into consideration both clinically and ethically impactful factors. Thus, it is imperative that clinicians have a sound understanding of the ethical concepts related to periviability, and how they apply to the clinical scenarios. In this section, an ethical framework for approaching this decision-making is presented.
Key ethical questions — Ethical questions that the clinician must consider in the care of the periviable neonate include:
●What interventions should be performed?
•Should resuscitation and intensive care measures (eg, intubation, chest compressions, administration of epinephrine, mechanical ventilation) be initiated in the delivery room?
•Are these interventions ethically impermissible, optional, or obligatory?
•Once intensive care measures (eg, intubation and mechanical ventilation) have been started, is it permissible to stop?
●What informs decision-making?
•Should these decisions be based upon what is known about outcomes of periviable birth?
•To what degree should parental preference factor into these decisions?
Rights and obligations of key stakeholders — The rights and obligations that we consider relevant to answering these questions include, but may not be limited to, the following:
●The infant has a right to treatment, when feasible, that has a reasonable chance of saving their life. The infant also has a right to mercy, meaning a right not to be subjected to painful procedures that are extremely unlikely to benefit them (ie, improve survival and/or decrease morbidity) [1].
●The parents/caregivers have a right to information they need to make informed decisions on their child's behalf. They have a right to decide what is done to their child, but that may, in rare situations, be overridden by the child's rights (eg, if they refuse a treatment that would clearly and significantly benefit the infant or demand one that would be harmful to their child).
●Clinicians have an obligation to present parents/caregivers with the relevant information, such as morbidity and mortality data (as well as the limitations of those data), and to help them with the profoundly difficult decisions for the care of infants in this age group. An honest presentation of the relevant information and the available options (including, if feasible, transfer to another institution with a different institutional policy) is paramount. The clinical team should recognize the enormous stress that decision-making in this setting causes parents/caregivers and work closely with them to reach management decisions together, based primarily on an assessment of the perceived benefits and burdens to the infant of treatments under consideration. In rare circumstances, the clinical team may determine that caregivers' preferences are clearly opposed to the child's interests, in which case those decisions may need to be overridden, by use of proper procedural channels as time allows.
For those infants that receive active resuscitation, as the neonate's clinical status changes over the course of hospitalization (and thus the prognosis changes), the clinical team should share that information with the parent/caregivers and revisit management decisions regarding life-sustaining treatments. For example, in some cases the initial decision to resuscitate and initiate intensive case measures may be reversed if the clinical course of the infant reveals that ongoing intervention is not beneficial and may be harmful to the patient [2].
Ensuring just care based on prognosis — The principle of justice requires that the same treatment approach be offered to patients with similar prognoses. For management of periviable infants, this means ensuring a consistent (just) approach to care for all infants with similar estimated outcomes, tempered in many cases by parental preferences.
Based on consideration of the above ethical questions, rights, and obligations, providers need to determine if resuscitation is ethically obligatory, meaning the anticipated benefits clearly outweigh the risk of harm to the infant. If it is not obligatory, then providers must determine if attempting resuscitation is permissible, meaning the benefits might outweigh burdens, or impermissible if burdens clearly outweigh benefits.
Periviable infants can be assigned to one of these three ethical categories based on prognosis, which can guide initiation of resuscitative and intensive care interventions, ensuring consistent (just) care for all infants with similar estimated outcomes:
●Poor prognosis – If the prognosis is very poor, the neonate should not be made to undergo any resuscitative and intensive care measures since the likelihood of benefit is disproportionally small when measured against the likelihood of harm. In this case, these procedures would be ethically impermissible and supportive comfort measures alone are provided.
●Favorable prognosis – If the prognosis is favorable, feasible resuscitative and intensive care measures should be provided and are ethically obligatory.
●Unclear prognosis – If the prognosis is worrisome or unclear, but survival is possible, it can be difficult to determine the relative benefit and burden of initiating resuscitative and intensive care measures for the infant. In this setting, clinicians should generally defer to the values and preferences of informed parents/caregivers. Attempted resuscitation in this setting is ethically permissible, but not obligatory.
Defining the boundaries of these three categories is challenging, but establishing institutional policies around them is a key method to ensuring just care. Review of local and published outcome data, as well as societal and national guidelines, is helpful when developing a consensus institutional approach to define these management categories. (See 'Establishing institutional policy' below and 'Outcomes' below and 'Society guideline links' below.)
OUTCOMES — In this section, we present key clinical outcome data and prediction tools used to inform decision-making. Based on analyses of the outcome data, prediction tools for survival, including the risk of profound disability, have been developed.
Survival — The likelihood of survival is the most important outcome to consider in decision-making for periviable infants. However, the reporting of this outcome varies somewhat in the available published studies, with some reporting only short-term survival (to hospital discharge) while others report long-term survival (24 months corrected age [CA] or longer). In addition, some studies select survival without profound neurodevelopmental impairment (NDI) as the primary outcome, which is typically assessed at 18 to 24 months CA.
Factors that impact survival, some of which are used in prediction tools, include the following [3-7] (see 'Prediction tools' below):
●Gestational age – Gestational age (GA) is the most commonly cited predictor of survival. Published survival rates based on GA (22 to <26 weeks) during the initial neonatal intensive care unit (NICU) admission for infants are summarized in the table (table 1) [8-22]. Data are presented in the table that date back over two decades. However, it should be noted that a significant increase in predicted survival at 22 and 23 weeks gestation has been reported in recent years. These data span broad geographic areas (including Western Europe, Japan, the United States, and Canada), with a range of follow-up from six months to six years. Key observations from these data include:
•Survival rates rise steadily as GA increases from 22 to 25 weeks.
•Survival for all GAs has increased over time.
•There is variability in outcomes between studies, which may reflect differences in care (active versus comfort care).
●Birth weight – A 2008 report from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network of 4446 infants born between 1998 and 2003 with birth weights (BWs) >400 g and GA 22 and 25 weeks demonstrated that each 100 g increase in birth weight reduced the risk of death or neurodevelopmental disability for infants similar to the risk reduction from a one-week increase in GA [4]. In a 2019 report from the NICHD Neonatal Research Network of 205 infants born between 2008 and 2015 with a BW <400 g and GA between 22 and 26 weeks, 26 percent of actively treated infants survived to discharge, although NDI was common [23].
●Approach to initial management – Approach to initial management, specifically whether or not periviable neonates are actively resuscitated at birth, has been shown to influence overall survival rates. When accounting for variation in initial management among centers, studies report improved survival for those centers that generally provide more active resuscitative efforts compared with those that provide comfort measures only. This is supported by the following studies [24-29]:
•A retrospective study from the Netherlands reported that implementation of guidelines supporting active initial care of infants born at 24 weeks GA resulted in an increase in NICU admission rates and postnatal survival [30].
•Data from the NICHD Neonatal Research Network of infants (GA <27 weeks) born between 2006 and 2011 showed that between hospital variation in survival among infants born at 22 to 24 weeks GA appeared to be due in part to whether active treatment was initiated [24]. Most centers provided active intervention for infants born between 25 and 26 weeks GA.
•The highest published survival rates, 78 percent for infants born 22 to 23 weeks GA and 89 percent for those born at 24 to 25 weeks GA, come from a center that actively resuscitates all infants born ≥22 weeks [25]. Of note, this study excluded infants who died in the delivery room.
Having routine active initial management may provide better outcomes than trying to select certain infants prior to birth for active resuscitation. In other words, one reason for improved survival in centers that provide more active resuscitative efforts is that those who more often attempt resuscitation at the lowest gestational ages may develop greater proficiency.
This is supported by a retrospective cohort study of 112 infants born at 22 weeks GA in two hospitals with different approaches to initial management of periviable neonates. Infants treated at a hospital with proactive management of all 22 week GA infants had in-hospital survival rates higher than those at an institution with selective resuscitation based on physician and parental preference (53 versus 8 percent, respectively) [29]. Among the subgroup of infants receiving proactive care, including antenatal steroids and neonatal resuscitation, survival was also higher in the center that routinely provided proactive care (53 versus 19 percent, respectively).
A trend for increased active treatment was reported in a study from a large United States database of neonates born at 22 weeks to <26 weeks, which found that the frequency of active treatment for periviable neonates increased from 45.7 percent in 2014 to 58.8 percent in 2020 [31].
●Antenatal corticosteroid therapy – The increased survival associated with antenatal corticosteroid therapy for periviable infants is discussed separately. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Less than 37 weeks'.)
●Sex – Male preterm infants have a higher mortality rate than female preterm infants [32,33].
Neurodevelopmental outcome — Neurodevelopmental impairment (NDI) is a major long-term complication of periviable birth. NDI includes impaired cognition, motor and neurosensory deficits, and behavioral and psychological problems. The prevalence of these impairments from cohorts of survivors following birth at 22 to <26 weeks gestation is displayed in the table (table 2) [4,14-16,22,34-36]. (See 'Definitions' above.)
Several factors impact neurodevelopmental outcome, some of which also affect survival and are used in prediction tools for periviable outcome.
●Gestational age – The likelihood of surviving without long-term major NDI increases with increasing GA. In a retrospective cohort study 720,901 infants born between 1983 and 2010, the estimated probability of surviving to age 25 years without disability (defined in this study as intellectual disability, autism spectrum disorder, or cerebral palsy) ranged from 4 percent for infants born at 22 weeks GA to 78 percent for infants born at 28 weeks GA, to 97 percent for infants born at >39 weeks GA [37]. One limitation of this study is that these data cover a long time period, including an era with very low survival rates at the lowest gestational ages. Thus, the current probabilities for survival without NDI may be higher than reported here, but the trend of improvement with increasing GA remains.
●Approach to initial management – Reported neurodevelopmental outcomes vary depending on whether maximal resuscitative efforts were made. (See 'Limitations of the data' below.)
•In a NICHD Neonatal Research Network study conducted between 2006 and 2011, disability-free survival was higher among infants born at 22 weeks GA who received active intervention (n = 79, 15.4 percent, 95% CI 8.8-25.4) compared with the overall rate for all infants born at 22 weeks gestation with those who did not receive active intervention (n = 3753.4 percent, 95% CI 1.9-5.9) [24].
•In a recent report of 248 infants managed at a single institution where active treatment was routinely provided to all periviable infants, survival without severe NDI at 18 to 22 months CA was seen in approximately 50 percent (41 percent of infants born at 22 to 23 weeks GA; 53 percent of those born at 24 to 25 weeks GA) [25]. However, follow-up data were not available for 45 patients (18 percent) from the original cohort and infants who died in the delivery room were not included in the analysis.
●Trends over time – Neurodevelopmental outcomes have improved over time with advances in perinatal and neonatal care.
•In a multicenter NICHD Neonatal Research Network study of infants born at 22 to 24 weeks GA, neurodevelopmental outcomes were evaluated at 18 to 22 months CA and compared across three consecutive birth-year epochs (2000 to 2003, 2004 to 2007, and 2008 to 2011) [36]. After adjusting for differences in baseline patient characteristics, survival without NDI increased from 16 percent in epoch 1 to 20 percent in epoch 3 (adjusted relative risk [RR] 1.59, 95% CI 1.28 to 1.99). The study did not detect a significant trend over time in the subgroup of infants born at 22 weeks gestation; however, this subgroup was small and may have lacked sufficient power to detect a significant difference.
•Another study reported improved neurodevelopmental outcomes among survivors of extremely preterm birth between the 1995 Epicure birth cohort (23 percent survival without NDI) and a 2006 Epicure 2 birth cohort (34 percent survival without NDI) [38]. Rates of survival with severe NDI were similar in both cohorts (18 and 19 percent, respectively). However, three-year follow-up data were incomplete for the 2006 cohort, which limits the interpretation of these findings.
Long-term neurodevelopmental outcomes of extremely preterm (EPT; GA <28 weeks) and extremely low birth weight (ELBW) (BW <1000 g) infants are discussed in detail separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Extremely preterm infant'.)
Other morbidities — For infants born between 22 and <26 weeks gestation significant morbidities that may be experienced during the NICU course include:
●Severe intraventricular hemorrhage (IVH) (ie, grade III and periventricular hemorrhagic infarction, previously referred to as grade IV) (see "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis")
●Periventricular leukomalacia (PVL) (see "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'White matter injury')
●Necrotizing enterocolitis (NEC) (see "Neonatal necrotizing enterocolitis: Clinical features and diagnosis")
●Bronchopulmonary dysplasia (BPD) (see "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis")
●Severe retinopathy of prematurity (ROP) (ie, stage ≥3) (see "Retinopathy of prematurity (ROP): Risk factors, classification, and screening", section on 'Classification')
●Sepsis (see "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation")
The risk of these morbidities is highly dependent on GA, as summarized in the table (table 3) [9,11,12,14,15,17-19,34].
●United Kingdom – In the United Kingdom, the British Association of Perinatal Medicine (BAPM) has published a framework (BAPM Perinatal Management of Extreme Preterm Birth before 27 weeks of gestation) to guide management of infants born before 27 weeks gestation based on data predicting survival and neurodevelopmental outcome [39,40]. This guideline contains a BAPM outcome tool based on GA to be used clinically for parental counseling and as an aide to inform care management decisions.
Limitations of the data — Although there is an abundance of published data on survival and morbidity for periviable infants, there are limitations that clinicians should be aware of when interpreting these data, particularly when comparing one study to another [41].
●Differences in study design – Reported outcomes in different studies may vary depending on inclusion criteria and definitions used for key outcomes [42].
•Inclusion/exclusion criteria
-Definition of birth – Survival rates for periviable infants differ because of variations on how live births are defined, primarily dependent on the inclusion of still births (fetuses alive at the onset of labor) [43].
-Selective exclusion – Study results may differ if subgroups of infants are not included in the analysis. For example, in one study with the best reported survival rates for infants born at 22 and 23 weeks GA without NDI, infants who died in the delivery room were not included in the analysis [25].
•Outcome definition – Outcome measures amongst studies vary from survival alone, survival with developmental impairment (NDI, which may vary from severe to mild impairment) and survival without NDI. In addition, other variables include the timing of survival assessment (after delivery, at discharge from the neonatal intensive care, or later), as well as the timing of the assessment of neurodevelopmental outcome as noted below.
●Uncertainty in GA estimates – Clinicians should recognize that there is often a margin of error in estimating GA. Thus, when using GA to predict the likelihood of survival for a periviable infant, the assigned GA should usually be considered a range rather than an exact number. The exception to this could be a pregnancy resulting from in vitro fertilization, wherein dating can be assumed to be accurate.
Typically, the GA of the fetus is determined by date of the last menstrual period (LMP) and/or ultrasound. For the latter, the timing of the ultrasound affects the accuracy (eg, the estimated GA may be off by five to seven days when the ultrasound is performed before 14 weeks gestation and as many as 14 days when performed beyond 22 weeks) [44,45]. Thus, depending on the date of the initial ultrasound assessment, an imminent delivery believed to be at 23 weeks could be under 22 weeks, with virtually no chance of survival, or more than 24 weeks, with a greater than even likelihood of survival if resuscitation and intensive care measures are initiated. The American College of Obstetricians and Gynecologists (ACOG) has stated that a pregnancy should be considered suboptimally dated if the estimated time of delivery is not confirmed or revised by ultrasound before 22 weeks. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Best estimate of delivery date' and "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Suboptimally dated pregnancies'.)
Postnatal assessments of GA are also prone to error because fetal development of external features is variable. Most postnatal assessment tools are only accurate to within one to two weeks gestation. Thus, it is not possible to accurately differentiate a neonate at 23 weeks from another at 22 or 24 weeks based on physical examination in the delivery room. The best obstetrical estimate should be used when counseling parents or making decisions unless there is a profound discrepancy between physical appearance and the obstetrical estimate of GA. (See "Postnatal assessment of gestational age", section on 'Methods of postnatal assessment'.)
●Uncertainty regarding outcomes beyond early childhood – Most studies on neurodevelopmental outcomes of periviable birth (including the data used in the NICHD outcome estimator [4,5]) have reported findings based upon follow-up evaluations of survivors at 18 to 26 months CA [4,5]. There is good but limited evidence that neurodevelopmental outcome is more accurately assessed at school age since there is potential for cognitive recovery as the brain continues to develop. Thus, predictions for a given newborn based on reported assessments of similar children at 18 to 26 months may overestimate the true likelihood of moderate or severe disability in the long-term. However, infants who are assessed as having severe NDI at 18 to 26 months CA are likely to continue to have significant NDI at an older age. In addition, assessment in infancy and early childhood identifies infants who may benefit from early intervention. Thus, though reported outcome measures of severe NDI at 18 and 26 months CA may overestimate the likelihood of severe impairment later in childhood, they remain clinically relevant when discussing management options with parents and caregivers. Moreover, assessment of NDI at 18 to 26 months may underestimate some long-term morbidities such as ADHD, autism, and learning difficulties.
The impact of age on assessment of neurodevelopmental outcome in EPT infants, including supportive evidence is discussed in greater detail separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Formal clinical assessment'.)
●Impact of initial neonatal management – Interpretation of outcome data must consider whether or how often resuscitation was attempted in the cohort, because outcomes vary considerably depending on whether maximal resuscitative and obstetrical efforts were made [1,24-28,46].
The impact of providing active treatment versus comfort measures only on survival is particularly evident in neonates born at <24 weeks GA. In retrospective studies, survival rates for neonates born at 22 to 23 weeks GA were considerably higher at centers where active treatments were more commonly provided to such neonates compared with centers that less frequently provided active treatment to these neonates [24]. (See 'Survival' above.)
●Use of antenatal corticosteroids and other differences in obstetrical and neonatal care – Changes in maternal and neonatal care practices have also influenced the outcome of periviable newborns and need to be accounted for when interpreting outcome data [17]. In particular, the administration of antenatal corticosteroids is associated with improved outcome for periviable infants [15,47]. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Candidates for a first ACS course by gestational age'.)
Prediction tools — Tools that predict outcome for periviable infants have been developed based on the outcome data that have identified the key modifying factors [4,6,24,39].
●United States – In the United States, a predictive tool initially developed and published in 2008 by the NICHD Neonatal Research Network was updated and validated by cohorts of patients from the NICHD Neonatal Research Network from 2006 to 2012 and from the Vermont Oxford Network from 2006 to 2012 and 2013 to 2016 [4,5]. The updated NICHD Extremely Preterm Birth Outcomes Tool derived from these results predicts survival and neurodevelopmental outcome for EPT infants (GA <28 weeks) at 18 to 26 months CA based on:
•Gestational age
•Birth weight
•Sex of the infant
•Singleton versus multiple births
•Administration of antenatal steroids
This calculator is not intended to be predictive of individual infant outcomes but rather provides an estimate of possible outcomes based on patient characteristics. While it may prove helpful for counseling and clinical decision-making regarding resuscitation, it is not intended to be the sole basis for care decisions, so the clinician must consider other relevant factors when counseling parents/caregivers regarding management decisions. This includes negative effects of long-standing fetal compromise and/or maternal and fetal infection, and the potential effects of intensive intervention that may impact local outcomes.
It should also be noted that the survival and disability estimates have improved significantly from those provided in the earlier version of this model, which was based on a cohort of infants born over 20 years ago. The updated model showed that while the factors influencing outcomes remained the same between the two versions, outcomes did improve. Thus, periodic updating of the tool will be needed so that estimates of predicted outcome can be as accurate as possible and remain clinically relevant.
Finally, this tool is only applicable at birth, as the likelihood of survival for an infant born at borderline gestational age increases significantly over the first days and weeks of life [21,48].
ESTABLISHING INSTITUTIONAL POLICY
Guiding principles — Every facility that cares for high-risk pregnancies should have an institutional policy in place to guide the management of periviable neonates so that practice among clinical staff is consistent. This ensures that all periviable neonates are treated justly (ie, the same treatment options made available for neonates with similar prognosis).
Key aspects of establishing institutional policies for periviable infants include [49,50]:
●Ethical framework – Institutional policies should use a framework that respects the rights of the infant and parents/caregivers (parental/caregiver authority), addresses the obligations of the clinical team (beneficence and non-maleficence), and ensures equal treatment for periviable infants with similar prognoses (justice). (See 'Ethical framework' above.)
●Evidence-based framework – Institutional policies should be based upon review and accurate interpretation of relevant and current data on outcomes in periviable neonates. These data should encompass the full range of obstetric and neonatal treatment options (eg, antenatal steroids and active neonatal resuscitation and intensive care support). (See 'Outcomes' above.)
●Multidisciplinary approach ─ Assembly of an institutional multidisciplinary group to provide input for the guidelines, including neonatologists, neonatal intensive care unit (NICU) nurses, maternal-fetal medicine (MFM) physicians, and a representative of the hospital ethics committee. The group is tasked with establishing guidelines to answer key clinical questions based on their review of the available local and published outcome data, societal and professional recommendations [40,51-54], ethical issues and relevant rights of the key stakeholders for the established prognosis categories. (See 'Outcomes' above and 'Rights and obligations of key stakeholders' above and 'Ensuring just care based on prognosis' above.)
Key clinical questions — The framework for decision-making policy regarding resuscitation for periviable newborns is based on the answers from the institution's multidisciplinary team to the following three fundamental questions regarding prognosis:
●At what minimal chance of survival, or survival without significant disability, should resuscitation be offered?
●Above what chance of survival, or survival without disability, should resuscitation be considered ethically obligatory, and provided for all newborns?
●To what extent should anticipated disability factor into resuscitation decisions?
OUR APPROACH — Our center at Yale New Haven Children's Hospital has established and updated the following approach to the treatment of periviable infants.
Assessment of prognosis — Prognostic thresholds were established after review of outcome data and the ethical issues and rights of the key stakeholders that answered the key clinical questions. Our center selected the National Institute of Child Health and Human Development (NICHD) Extremely Preterm Birth Outcomes Tool to aid in establishing prognostic categories. The NICHD Extremely Preterm Birth Outcomes Tool predicts outcomes (survival and neurodevelopmental outcome) based upon gestational age (GA), birth weight (BW), sex, plurality, and the use of antenatal corticosteroids. (See 'Key clinical questions' above and 'Prediction tools' above.)
Our institutional policy for resuscitation and critical care interventions for periviable infants reached by group consensus is based on the following prognostic categories:
●Impermissible (poor prognosis) threshold – Attempted resuscitation is considered impermissible <22 weeks GA and will not be offered or attempted. Although there are no published data for likelihood of survival below 22 weeks GA if resuscitation is attempted, survival for this age group was felt to be exceedingly low and significantly below 10 percent based on the very few case reports of survival and biologic evidence that maturation of organ function (eg, lung function) is insufficient to sustain extrauterine life.
●Obligatory (favorable) threshold – Resuscitation is considered obligatory if treatment would yield a chance of ≥66 percent for survival without profound disability based on the NICHD outcome estimator. Profound disability is defined by the NICHD outcome estimator as a Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive score that was untestable or a Gross Motor Function Classification System (GMFCS) level score of 5 (on a scale of 0 [normal] to 5 [most impaired]) [5].
It is recognized that our choice of 66 percent as the threshold for obligatory is a subjective one. In our discussion, the group noted that the British Association of Perinatal Medicine (BAPM Perinatal Management of Extreme Preterm Birth before 27 weeks of gestation) used a >50 percent chance of survival without severe disability [39,40]. Other institutions when developing guidelines must determine the appropriate threshold for their center.
●Permissible (unclear prognosis) – Infants that fall between the impermissible and obligatory thresholds have an uncertain prognosis. For these patients, the preference of the parents/caregivers should generally determine the extent of resuscitative efforts.
Prenatal management
●Prenatal counseling – During preterm labor, it is important for the care team to provide information to parents/caregivers on the potential outcome of the delivery of the periviable infant based on available data for the specific birth hospital setting. The team should understand and acknowledge the parents'/caregivers' values and preferences regarding the extent of care prior to the delivery.
In most cases, when an agreed-upon plan has been made prenatally, the clinical team should not deviate from it at the time of delivery based solely on the neonate's general appearance. However, deviating from an agreed-upon plan may be appropriate if the assessment in the delivery room provides new objective data that significantly alter the previously discussed prognosis (eg, if the neonate's BW is considerably lower than expected or there is a profound discrepancy between physical appearance and the obstetrical estimate of GA). When this occurs, the decision to deviate from an agreed-upon plan should be discussed with the parents/caregivers if possible [55].
●Antenatal corticosteroids – Administration of antenatal corticosteroids is recommended for women in preterm labor and is discussed separately. In our center, antenatal corticosteroids are offered to women starting at 22 weeks gestation, whereas, other centers use 23 weeks gestation. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Candidates for a first ACS course by gestational age'.)
Additional information on obstetric care guidelines regarding clinical management of pregnancies with threatened or imminent delivery at 200/7 to 256/7 weeks gestation is presented elsewhere. (See "Delivery of the low birth weight singleton cephalic fetus", section on 'Management at/near the limit of viability'.)
Postnatal management — Our general postnatal approach for resuscitation and intensive care measures for periviable infants is as follows.
●Below 22 weeks gestation – Resuscitation is not offered or provided due to the extremely low chance of survival, regardless of other factors. In this setting, the likelihood of benefit is disproportionally small when measured against the likelihood of harm.
●Beginning at 22 weeks gestation – Resuscitation options for parents are based on prognosis as determined by the NICHD Extremely Preterm Birth Outcomes Tool. (See 'Assessment of prognosis' above.)
•For neonatal outcomes with <66 percent chance of survival without profound disability, the values and preference of informed parents/care providers generally determine whether resuscitation and aggressive treatment are provided.
•For neonatal outcomes with ≥66 percent chance of survival without profound disability, resuscitation and critical care are considered obligatory and thus are provided. In this circumstance, expectant parents/care providers are made aware that this treatment will be provided. If they do not want resuscitation and if time allows, the option of maternal transport to another facility that offers a different approach (if available) is offered.
Exceptions may be made at the discretion of the attending clinician if there is additional or subsequent evidence that significantly worsens the prognosis (eg, certain congenital anomalies or profound growth restriction).
●Comfort care measures are provided for any infant that does not undergo resuscitative efforts or has life sustaining therapies withdrawn.
●Despite the determination that resuscitation for a periviable infant with a high likelihood of survival without profound disability is obligatory, a maternal right to autonomy and bodily integrity remain. That is, regardless of the status or prognosis of her fetus, a woman has the right to refuse any interventions on herself, including but not limited to antenatal steroids, fetal monitoring, induction of labor, or caesarian section.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Periviable birth".)
SUMMARY AND RECOMMENDATIONS
●Definition – Periviability is defined as the earliest stage of fetal maturity where there is a reasonable chance, although not a high likelihood, of extrauterine survival. (See 'Definitions' above.)
●Institutional policies – Every facility that cares for high-risk pregnancies should have institutional policies in place to guide the management of periviable infants so that practice among clinical staff is consistent. This ensures that all periviable infants are treated with the same treatment approach for infants with similar prognoses). (See 'Establishing institutional policy' above and 'Ensuring just care based on prognosis' above.)
Institutional policies should include (see 'Guiding principles' above):
•An ethical framework for identifying and addressing the relevant ethical management issues. (See 'Ethical framework' above and 'Terms related to medical ethics' above.)
•A system for reviewing and accurately interpreting the most current available outcome data that address the wide range of obstetric and neonatal treatment options. (See 'Outcomes' above.)
•Consensus of a multidisciplinary team on the answers to key clinical questions regarding management of periviable infants. (See 'Key clinical questions' above and 'Assessment of prognosis' above.)
●Factors that affect survival rates and the risk of NDI for periviable preterm infants include gestational age (GA), birth weight, sex, plurality, and the receipt of antenatal corticosteroids or active initial intervention (table 1 and table 2). (See 'Survival' above and 'Neurodevelopmental outcome' above.)
●There are significant morbidities seen during the NICU course (eg, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, severe retinopathy of prematurity) associated with periviability (table 3). The major long-term complication is neurodevelopmental impairment (NDI), which can include impaired cognition, motor and neurosensory deficits, and behavioral and psychological problems. The risk of profound NDI may guide initial management (table 2). (See 'Neurodevelopmental outcome' above and 'Other morbidities' above.)
●In our practice, the consensus approach we use in managing periviable infants is based on the best available prognostic data on survival and morbidity, and review of the relevant ethical issues and principles by a multidisciplinary team of clinicians and ethicists. (See 'Our approach' above.):
●In our center, prenatal care includes counseling parents/care givers regarding the potential neonatal outcomes, including an estimation of likelihood of survival and major morbidities, and the options regarding resuscitation. After discussion, informed parents/care givers provide the clinical team with their preference regarding care for their infant. (See 'Prenatal management' above.)
●In our center, postnatal care is based on prognostic categories. (See 'Postnatal management' above and 'Assessment of prognosis' above and 'Outcomes' above.)
•For neonates <22 weeks GA, resuscitation is not offered or provided since the prognosis is poor with an extremely low likelihood of survival. Thus, the likelihood of benefit is disproportionally small when measured against the likelihood of harm.
•Beginning at 22 weeks gestation, resuscitation options for parents are generally based on prognosis as determined by the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network Extremely Preterm Birth Outcomes Tool. This tool estimates the likelihood of survival and the likelihood of survival without profound disability based upon key prognostic variables (GA, birth weight, sex, plurality, and the use of antenatal corticosteroids). (See 'Assessment of prognosis' above.)
-For neonatal outcomes with ≥66 percent chance of survival without profound disability, resuscitation and critical care are considered obligatory and thus are provided. In this circumstance, expectant parents/care providers are made aware that this treatment will be provided. If they do not want resuscitation and, if time allows, the option of maternal transport to another facility that offers a different approach (if available) is offered.
-Exceptions may be made at the discretion of the attending clinician if there is additional or subsequent evidence that significantly worsens the prognosis (eg, certain congenital anomalies or profound growth restriction).
•Comfort measures are provided to any periviable infant who does not receive active resuscitative or intensive care interventions.
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Richard Ehrenkranz, MD, FAAP (deceased), who contributed to earlier versions of this topic review.
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