This is an executive summary of a workshop on the management and counseling issues of women anticipated to deliver at a periviable gestation (broadly defined as 20 0/7 through 25 6/7 weeks of gestation), and the treatment options for the newborn. Upon review of the available literature, the workshop panel noted that the rates of neonatal survival and neurodevelopmental disabilities among the survivors vary greatly across the periviable gestations and are significantly influenced by the obstetric and neonatal management practices (for example, antenatal steroid, tocolytic agents and antibiotic administration; cesarean birth; and local protocols for perinatal care, neonatal resuscitation and intensive care support). These are, in turn, influenced by the variations in local and regional definitions of limits of viability. Because of the complexities in making difficult management decisions, obstetric and neonatal teams should confer prior to meeting with the family, when feasible. Family counseling should be coordinated with the goal of creating mutual trust, respect and understanding, and should incorporate evidence-based counseling methods. Since clinical circumstances can change rapidly with increasing gestational age, counseling should include discussion of the benefits and risks of various maternal and neonatal interventions at the time of counseling. There should be a plan for follow-up counseling as clinical circumstances evolve. The panel proposed a research agenda and recommended developing educational curricula on the care and counseling of families facing the birth of a periviable infant.
The counseling and management of women at risk for delivering near the limit of viability, referred to in this document as the ‘periviable period’ (broadly defined as 20 0/7 through 25 6/7 weeks of gestation), remain one of the most challenging issues faced by obstetricians and neonatologists. When delivery is anticipated or occurs during this period, the health-care team and the family must quickly make complex, ethically challenging decisions—often in an emotionally charged and evolving setting. Such decision making continues through the newborn infant’s hospital course in the neonatal intensive care unit (NICU).1
Despite guidelines from professional societies regarding maternal and neonatal care at periviable gestations, many issues remain unresolved.2, 3, 4 For example: where should women at risk for periviable birth be cared for; when should tocolytic agents and antenatal corticosteroids be given to delay delivery and to advance fetal lung maturation; when should electronic fetal monitoring be instituted to assess the fetal status; when should cesarean delivery be offered for fetal indications; how should the potential benefits to the infant and the risks to the mother from cesarean birth at a periviable gestation be balanced; when and how should the family be counseled regarding these complex issues and what should the contents of such counseling be; and when and how should decisions regarding initial or continued intensive newborn care versus comfort care be made?
To address these issues, the Society for Maternal-Fetal Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Section on Perinatal Pediatrics of the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists convened a joint workshop, which was held concurrently with the annual meeting of the Society for Maternal-Fetal Medicine in San Francisco, CA, USA on 12–13 February 2013. This executive summary reviews the benefits and risks of obstetric and neonatal interventions related to periviable birth, provides an outline for counseling these patients, describes newborn outcomes after periviable birth, and outlines research and educational agendas regarding care and treatment of these patients. Suggested treatment outlines are based on review of the available literature and extrapolation from relevant articles by the expert panel.
There are numerous terms used to refer to preterm delivery at a very early gestational age (for example, extremely low gestational age, extreme preterm and very preterm), at a very small size (extremely low birth weight and micro preemie), of a very immature fetus (immature born and marginally viable) or near the limit of potential survival (margin of viability, border of viability, threshold of viability and periviable).5, 6, 7, 8, 9, 10, 11, 12, 13 Each encompasses a gestational age spectrum that includes high rates of mortality and severe morbidities among survivors at the lower end, and significantly higher rates of survival and survival without major disabilities at the upper end. We recognize that there is no ideal definition, and that no phrase precisely reflects all components of the epidemiology and the dilemmas associated with decision making during this time frame. We have opted for the phrase ‘periviable birth’, defined as delivery occurring from 20 0/7 through 25 6/7 weeks of gestation, to reflect the gestational age range in which survival rates range from 0% at 20 weeks to more than 50% at 25 weeks of gestation.
Morbidity and mortality rates and ethical dilemmas
Approximately 0.4–0.5% of all births occur at or before 27 weeks of gestation, and these account for over 40% of infant deaths14 and most neonatal deaths. Infants born at 20 and 21 weeks of gestation do not survive, irrespective of resuscitation efforts. The survival data for births at 22, 23, 24 and 25 weeks of gestation (excluding infants with birth weight lower than 401 g, greater than 1000 g or higher than the 97th percentile for gestational age; infants with ambiguous genitalia or major anomalies; and survivors not requiring mechanical ventilation) reported from the National Institute of Child Health and Human Development Neonatal Research Network were 6%, 26%, 55%, and 72%, respectively, at initial discharge from the hospital.15 Investigators from the same network later reported an additional 2.2% of extremely low gestational age infants (before 27 weeks and birth weight less than 1000 g) died after discharge and before 22 months of age.16 Many studies have noted that from the mid 1980s through the late 2000s, there has been an increasing rate of survival after periviable birth.15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 However, survival data for periviable births from the reports published since 2000 show remarkable variability in outcomes among studies15,21,24, 25, 26, 27, 28, 29 (Table 1). There are multiple reasons for this variation, some of which include nonmodifiable factors (for example, fetal sex and weight and singleton birth), modifiable factors (for example, intent to intervene, antenatal corticosteroid administration and life-sustaining interventions at birth), and study design and reporting features (for example, single center, regional or national data; definition of mortality; inclusion of all live births versus resuscitated newborns versus only those admitted to a NICU; Table 2). Other factors that might affect the reported survival are local practices and protocols for withholding or withdrawing intensive care after birth.
Data regarding long-term outcomes are likewise complex. Woods et al.31 reported the outcomes at 30 months of age for infants born at or before 23 weeks, at 24 weeks and at 25 weeks of gestation in 1995 in the United Kingdom and Ireland. These authors found a progressive decline in the proportion of children with ‘severe’ disability (Bayley Scales of Infant Development-II score 54 or lower) with increasing gestational age, ranging from 27% at 23 weeks to 19% at 24 weeks and 17% at 25 weeks of gestation. In the same cohort followed to 6 years of age, similar trends in the rates of ‘overall disability’ (a combined measure of cognition, neuromotor function, hearing and vision) were evident; 25%, 29% and 18% at 23, 24 and 25 weeks of gestation, respectively.32 A recent systematic review, published since the workshop was held, evaluated long-term neurodevelopmental impairment at 4–8 years among survivors born between 22 and 25 weeks of gestation. The risk of moderate-to-severe neurodevelopmental impairment decreased 6% (95% confidence interval (CI) 1.7–10.3%) for each week gained in gestational age.33 However, morbidities were common and the CIs for point estimates were wide: 43% (21–69%), 40% (27–54%), 28% (18–41%) and 24% (17–32%) at 22, 23, 24 and 25 weeks of gestational age, respectively. Importantly, survival after birth at 22 and 23 weeks of gestation was uncommon (n=12 and n=75, respectively). Severe neurodevelopmental impairment did not significantly decrease with increasing gestational age at birth.
When counseling parents, it is appropriate to present the data regarding the rate of survival and long-term disabilities separately, as the parents’ perspectives and the importance they give these may be different. Physicians should recognize that the parents’ views on what is a ‘severe’ disability may be different from those of the researchers or clinicians, who traditionally report the combination of death and severe disability together. Coping with a child’s behavior problem, considered a ‘minor’ disability in the published literature, may be difficult to handle for some families, while other families may be able to adapt more readily to disabilities typically considered to be major (for example, cerebral palsy).
An appreciation of the complex issues discussed above will help health-care providers to engage in counseling efforts without being biased by one’s personal values and experiences. Future studies are needed to develop accurate prediction models to permit better counseling of families based on their individual risks, rather than based on gestational age alone.
Ideally, all periviable births should occur in tertiary care centers with expertise in maternal–fetal medicine and the availability of the highest level of neonatal intensive care services. Maternity hospitals without such resources should develop partnerships with a tertiary care center, and the latter should maintain requisite resources, including timely availability of needed experts to care for the mother, her fetus and the newborn infant. Protocols should be developed to clarify the processes for consultation and transfer, as well as management before and during transfer (for example, antenatal corticosteroid administration for fetal maturation, magnesium sulfate for neuroprophylaxis, antibiotics for infection and group B streptococcus (GBS) prophylaxis).
Obstetric interventions at periviable gestations have included measures to delay delivery and to improve newborn outcomes when delivery is anticipated, for example: emergent cerclage, tocolytic therapy to delay delivery for antenatal steroid benefit, antibiotics for GBS prophylaxis or to reduce infection and prolong latency after preterm premature rupture of the membranes (PROM), antenatal corticosteroids to enhance fetal maturation and a willingness to intervene to prevent stillbirth or fetal trauma at delivery. The potential effect of these interventions on newborn outcomes as well as maternal well-being varies according to individual circumstances and with advancing gestational age.
Evidence-based data regarding obstetric interventions for those delivering at 20–25 weeks of gestation are limited, since these gestational ages were considered nonviable in the 1970s and early 1980s when many studies on these interventions for anticipated preterm births were conducted. Further, because a small number of women actually deliver at or before 25 weeks of gestation, most studies and meta-analyses involving these patients lack power to assess the effect of such interventions.
The workshop panel reviewed available literature and considered interventions and the levels of supporting evidence across the spectrum of periviable gestations.34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 Some of these interventions pose little risk to the mother, while others impose a significant burden.
Tocolytic therapy is proposed to reduce uterine activity for the purpose of delaying delivery to increase the time for antenatal corticosteroid effects. However, data regarding currently available therapeutic tocolytic agents fail to consistently demonstrate either pregnancy prolongation beyond 24–48 hours or newborn benefits, and no studies specifically address women with preterm labor or PROM at 20–25 weeks of gestation.
Physical examination–indicated cervical cerclage is performed when the fetal membranes are seen to bulge to or past the external cervical os in the absence of contractions. Observational studies describe that physical examination–indicated cerclage, performed at an average gestational age of 22 weeks, can be associated with a mean pregnancy prolongation of 7–9 weeks, compared with 2–3 weeks for those treated without cerclage placement, as well as increased live birth and neonatal survival.35, 36, 37, 38
Antenatal corticosteroid administration is one of the most effective antenatal interventions to improve infant outcomes.39, 40, 41, 42, 43 Lung tissue in explant culture from 12–24 week human fetuses has been shown to respond to corticosteroids with an increase in epithelial maturation and the appearance of lamellar bodies.39 Data from the Eunice Kennedy Shriver Neonatal Research Network observational cohort revealed death or neurodevelopmental impairment at 18–22 months to be lower for infants exposed to antenatal corticosteroids and born at 23 weeks of gestation (83.4% versus 90.5%; adjusted odds ratio (AOR) 0.58 (95% CI, 0.42–0.80)), at 24 weeks (68.4% versus 80.3%; AOR 0.62 (95% CI, 0.49–0.78)), and at 25 weeks (52.7% versus 67.9%; AOR 0.61 (95% CI, 0.50–0.74)), but not at 22 weeks of gestation (90.2% versus 93.1%; AOR 0.80 (95% CI, 0.29–2.21)).40 Death, intraventricular hemorrhage (IVH) or periventricular leukomalacia and death or necrotizing enterocolitis were also significantly less frequent among infants born at 23, 24 and 25 weeks of gestation after antenatal corticosteroid exposure. The benefits regarding reduced death persisted through 18–22 months (OR 0.59 (95% CI, 0.53–0.65)) for infants born at 22–25 weeks of gestation. Similarly, Mori et al.41 reported that infants exposed to antenatal corticosteroids before birth at 24–25 weeks of gestation had less frequent respiratory distress syndrome (OR 0.77 (95% CI, 0.60–0.98]), less frequent severe IVH (OR 0.49 (95% CI, 0.36–0.67)) and lower mortality (OR 0.65 (95% CI, 0.5–0.86)) compared with unexposed infants at the same gestations. In fact, even among the infants born at 22–23 weeks of gestation, antenatal corticosteroid exposure decreased mortality rates (OR 0.72 (95% CI, 0.53–0.97)). In 2008, Tyson et al.25estimated that antenatal corticosteroid administration increased the ‘functional’ (in terms of maturity) gestational age of those born at 22–25 weeks by 1.1, 1.2 and 1.3 weeks for survival, death or profound impairment, and death or any impairment, respectively.
Magnesium sulfate for neuroprotection has been studied among women at risk for imminent early preterm birth in five randomized controlled trials, including women recruited at 24–25 weeks of gestation.44 Overall, magnesium sulfate treatment reduced cerebral palsy (relative risk (RR) 0.68 (95% CI, 0.54–0.87)) and substantial gross motor dysfunction (RR 0.61 (95% CI, 0.44–0.85)) among survivors without increasing mortality (RR 1.04 (95% CI, 0.92–1.17)). Similar effects were seen with administration before 30 weeks of gestation for any cerebral palsy (RR 0.69 (95% CI, 0.52–0.92)), moderate-to-severe cerebral palsy (RR 0.54 (95% CI, 0.36–0.80)) and death (RR 1.00 (95% CI, 0.87–1.15)). However, data specific to those treated at 20–25 weeks are not available.
Intrapartum antibiotic prophylaxis against GBS reduces newborn infection and antibiotic treatment during conservative management of preterm PROM both prolongs pregnancy and reduces newborn infections. Studies of these interventions have included only limited numbers of women near the limit of viability and specific data for those at 20–25 weeks of gestation are lacking.
If a decision is made to provide intensive interventions for an infant in the periviable period, a second decision is required regarding the mode of delivery. This second decision can be divided in two: Is routine cesarean delivery appropriate for all such pregnancies? And, if not, will emergency cesarean delivery be considered to prevent trauma, stillbirth or fetal asphyxia for specific indications? The published literature regarding cesarean delivery for periviable birth is limited by a lack of adequate data reflecting the causes, interventions and contribution of current practices on outcomes related to cesarean delivery for periviable births.45, 46, 47, 48, 49 Further, randomized controlled trials of adequate size regarding planned cesarean delivery compared with planned vaginal delivery for periviable births have not been performed. Currently available data do not consistently support routine cesarean delivery to improve perinatal mortality or neurological outcomes for early preterm infants.45 There is no clear evidence that routinely performed cesarean delivery improves survival or long-term outcomes with growth restriction, and data suggesting improved outcomes with cesarean delivery for fetal malpresentation are limited.49 Alternatively, cesarean delivery in the periviable period incurs greater maternal morbidity, both immediately postoperatively and for future pregnancies, which must be considered in the risk–benefit balance when counseling women.
Within this framework, a team approach to counseling is recommended for those presenting at 20 or more weeks of gestation. The use of different obstetric interventions should be based on an individual analysis of the risks and benefits. When death is anticipated, the parents should be informed about the option of termination of pregnancy if this is consistent with regional statutes. A plan for re-evaluation and follow-up counseling should also be in place. Importantly, providers and families should understand that initiation of intervention to enhance outcomes (for example, antibiotics for preterm PROM and antenatal corticosteroid administration) does not mandate that all other aggressive interventions (for example, cesarean delivery) be undertaken regardless of clinical circumstances in the periviable period.
Optimally, guidance regarding perinatal management of anticipated or imminent periviable birth would be offered based on a firm knowledge of the likelihood of infant survival and a known likelihood of long-term morbidities. Gestational age alone and currently available predictive algorithms do not provide information that is sufficiently accurate or generalizable. Regardless of local or regional differences, there are substantial current data supporting that infants born at or before 21 weeks of gestation do not survive after birth regardless of aggressive intervention, and that the majority of infants born at or beyond 24 weeks of gestation do survive if live born and resuscitated. Alternatively, at 22–23 weeks of gestation, the majority of live-born resuscitated infants will not survive, and it is likely that local and other individual factors will have the greatest effect on outcomes for these infants born at the cusp of viability. In certain circumstances (for example, unknown or irregular menstrual history with late prenatal care), gestational age cannot be determined accurately. In this circumstance, gestational age is estimated based on data available when periviable birth is imminent, and the accuracy of this estimate should be considered during counseling and decision making.
Table 3 offers guidance based on current evidence and expert opinion. In many cases, data specific to the periviable period are lacking, so guidance is offered based on extrapolation from available data regarding interventions at more advanced gestational ages. Interventions to delay delivery before 22 weeks of gestation may not succeed in prolongation of pregnancy. In such circumstances, it is appropriate to withhold continued intrapartum interventions for fetal benefit, neonatal resuscitation or both, despite initiation of aggressive therapy. With delivery before 22 weeks of gestation, interventions that significantly increase maternal morbidities (for example, cesarean delivery) should be avoided, where possible, and the live-born infants should be offered comfort care. Because most newborns at 24–25 weeks of gestation will survive if resuscitated, efforts to prolong pregnancy, intrapartum interventions for fetal benefit and neonatal resuscitation should generally be offered, if appropriate. At 22–23 weeks of gestation, management decisions will need to be made based on whether the fetus is considered potentially viable based on individual clinical circumstances and whether the family desires aggressive measures to improve the potential for newborn survival after birth. In general, those born at 23 weeks of gestation should be considered potentially viable, as survival with resuscitation is 26–28% or more. Those considered nonviable at 22–23 weeks of gestation can be treated similarly to pregnancies at 20–21 weeks of gestation, while those considered potentially viable should be treated in a manner consistent with similar pregnancies at 24–25 weeks of gestation. If feasible, delivery of potentially viable infants should be undertaken in settings in which resources are available to care for extremely small and immature infants. This approach has the potential to increase the opportunity for survival and reduce morbidities among survivors.
Optimally, decisions regarding newborn resuscitation will be made after family counseling. Such counseling cannot be provided before delivery in all cases, as periviable birth often occurs emergently. Where detailed family counseling and input cannot be accomplished before delivery, follow-up counseling should be performed after initial newborn evaluation and care and should incorporate information available, such as the newborn’s initial response to intervention. It is emphasized that preterm infants born in the periviable period do not survive without life-sustaining interventions after birth, regardless of obstetric interventions.
It is expected that the team responsible for stabilizing the periviable infant will have successfully completed training provided by the Neonatal Resuscitation Program and be competent to implement all of the components of the International Liaison Committee on Resuscitation neonatal guidelines.51 It is helpful to carry out simulated scenarios to make sure the processes are implemented smoothly. Elements of successful stabilization include a preresuscitation checklist to evaluate equipment functionality, clearly assigned roles and responsibilities for each person involved in newborn resuscitation, and adherence to the Neonatal Resuscitation Program algorithm.52 After stabilization, a debriefing session can provide time for self-reflection and help improve the function of the group for future resuscitations. The goal of the initial stabilization of the periviable infant is no different from that for an infant at a more advanced gestational age. However, because of extreme fetal immaturity and small size, there are special considerations (Table 4). The feasibility of enhancing placental transfusion by delaying cord clamping for up to 30 seconds should be explored. Neonatologists, neonatal fellows or senior respiratory therapists, if available, should intubate these newborns to keep the number of intubation attempts to a minimum. If effective pulmonary ventilation is established, cardiopulmonary resuscitation (CPR) is rarely needed. In one study, the chance of disability-free survival was only 14% in extremely low-birth-weight infants who attained a 5-minute Apgar score <2 after CPR in the delivery room, indicating that prolonged CPR is a marker for higher mortality rates.52
Hypothermia is a major threat to the survival of a periviable newborn. In a cohort of over 500 infants born at or before 24 weeks of gestation, 72% had an admission temperature below 36 °C and 34% were below 34 °C.53 For every 1 °C decrease in admission temperature, the odds of late-onset sepsis increased by 11% (OR 1.11; 95% CI, 1.02–1.20), and risk of death increased by 28% (OR 1.28; 95% CI, 1.16–1.41). The World Health Organization and the International Liaison Committee on Resuscitation recommend that the delivery room should be at least 25 °C (77°F) to prevent neonatal hypothermia.54 Other steps include using wool or plastic hats, wrapping with polyethylene occlusive and using a thermal gel mattress.
The golden hours
Some experts consider the first 48–72 hours after resuscitation of extremely premature infants as ‘golden hours’ during which infants appear to transition from intrauterine to extrauterine life. Apparent stability is often followed by deterioration, most likely due to failure of multiple organ systems and in some cases aggravated by hypothermia. Even if hypothermia is prevented in the delivery room, many periviable infants become hypothermic during transfer to the NICU, potentially compounding metabolic acidosis. The lungs of such infants may be so immature that it may be difficult or impossible to ventilate them. Over half of preterm infants at periviable gestations manifest low mean blood pressure values during the first 3 days. As there are no evidence-based guidelines for either defining ‘hypotension’ or its treatment, the health-care team should assess the overall status of the infant prior to deciding on fluid, medication and other interventions. However, as physiological functions are interconnected, management of one ‘clinical problem’ may affect others. For instance, an attempt to correct serum electrolyte imbalance might lead to fluid overload and adversely affect the respiratory and cardiovascular functions. Thus, one should plan for vigilant monitoring to assess rapidly changing physiological functions and to fine-tune management options.
The first week
Critical to the continued survival of the periviable infant are respiratory and cardiovascular support; fluid, electrolyte and nutritional management; treatment of acid–base imbalances; and utilization of cerebral protection measures.27 Periviable infants require all components of intensive care, but their needs are often more acute with a narrow margin for error. For instance, because of extreme thinness of the skin and subcutaneous tissue, there is a risk of profound water loss unless a neutral thermal temperature environment with high humidity is maintained. Slight imbalance in administered fluid volume could compromise cardiac, respiratory and renal functions. The role of noninvasive respiratory management in improving outcomes has not been well studied in periviable infants.
Intracranial hemorrhage is a major neurological complication in the first week of life for periviable infants. Antenatal corticosteroids are known to reduce the occurrence of patent ductus arteriosus and IVH.41, 42, 43,55, 56, 57, 58, 59 Systematic reviews and meta-analyses of the studies of prophylactic postnatal indomethacin have confirmed the significant reduction in severe IVH. In 14 trials including over 2500 newborns, a 35% reduction in severe IVH was evident (RR 0.66 (95% CI, 0.53–0.82), P<0.001).58 However, a well-conducted study of prophylactic indomethacin did not show a benefit on neurodevelopmental outcomes, despite a reduction in severe IVH (Grades 3 and 4) from 13 to 9%.59 The demonstrated reduction in severe IVH, serious pulmonary hemorrhage and the need for surgical ligation of patent ductus arteriosus59 may well be considered significant benefits by families.
Optimal nutrition is of critical importance to the periviable infant, as is the provision of human milk, which has been shown to decrease necrotizing enterocolitis and mortality rates. Initial intravenous therapy should contain amino acids, and optimal total parenteral nutrition should be started in the first 24 hours after birth. Mothers should be encouraged and taught to express their breast milk. Breast milk expression within 6 hours of delivery is associated with increased production and a longer duration of breast milk feeding. Delay of enteral feeding for a prolonged period is no longer indicated, as early institution of trophic feeds has been demonstrated to be beneficial.
While there is intrainstitutional and interinstitutional variation regarding how the components of intensive care management for the periviable infant are administered, the effect of such practice variations on survival and morbidity rates needs to be assessed.
The goal of family counseling regarding anticipated or imminent periviable birth is to provide objective information in a compassionate manner, to permit shared decision making and to support the family. Although developing a standardized approach to counseling is important, there cannot be a single approach for all families. The health-care team should be prepared to tailor their approach and language to family needs and preferences (Table 5).
Counseling should be a bi-directional, collaborative and ongoing process. Often, families in crisis do not recall many key components of the counseling. Some parents only want to know ‘the big picture,’ while others wish to receive detailed information and statistics.60 Counseling of the pregnant woman can be directive when appropriate (Table 5).50 Some families want to be directed in their decision making, whereas others want to have an active role in making their own decisions. Some parents wish other family members or key supporters to participate in the process. Counseling should continue after the birth of the infant, preferably using designated personnel to update the family during the first hours and days after delivery.
Components of counseling
Critical components in counseling will vary depending upon whether it is done before birth, after birth or both; the likelihood of survival; and the likelihood of long-term disability. Depending upon the underlying cause of imminent periviable delivery, the discussion may include the benefits and risks of various obstetric interventions and the utility and timing of transfer to a tertiary care obstetric and neonatal facility. Discussion of the alternatives to and rationale for or against active maternal and neonatal intervention are appropriate. Institutional, regional or national data regarding outcomes should be provided as available. Although there are visual and Internet tools that augment counseling, their effect on patient satisfaction, understanding and decision making have not been well studied.
Depending on circumstances, discussion of options for redirecting or withdrawing life-sustaining interventions can be brought up either at the initial meeting or at a subsequent meeting. Whenever comfort care is offered, it should be clarified that appearance at birth and Apgar scores are of limited prognostic value, and that comfort care is an approach to caring for the newborn rather than being considered ‘no care.’ Health-care providers should avoid statements such as ‘doing everything,’ ‘the parents want nothing done’ or ‘there is nothing we can do.’ Provision of comprehensive palliative and family-centered support is a very important aspect of medical care.
It should be emphasized that management decisions are not necessarily irrevocable. Interventions aimed at improving survival may be initiated prenatally, but a final decision to not institute life-sustaining interventions at the time of delivery can still be appropriate, particularly if the shared decision is that the predicted likelihood of newborn complications that may affect survival and adverse long-term outcomes is considered to be too high. The shared decision regarding management may change with time, and the team should not be ‘locked’ into previous decisions, particularly when clinical circumstances change.
Educational needs and knowledge gaps
Table 6 outlines the recommendations for research and education developed during the workshop. Although this listing is not complete, we anticipate that it can provide guidance in setting priorities for research and education regarding care and counseling regarding periviable birth.
Perhaps the most controversial aspect of the workshop, and difficult aspect of caring for a woman at risk for periviable birth and her periviable newborn, is the lack of highly predictive models for infant morbidities and mortality rates. Estimated gestational age is available before birth based on menstrual dating, ultrasound or both, but the actual conception date is rarely known. The division between 1 week and the next is an arbitrary cutoff that does not reflect continuous growth and maturation (for example, a 23 6/7-week and a 24 0/7-week infant (1 day discrepant) are likely more similar in size and maturity than a 23 0/7-week infant and a 24 6/7-week infant (13 days discrepant)). Although fetal sex, plurality and antenatal treatments (for example, antenatal corticosteroids, magnesium sulfate for neuroprotection and antibiotic treatment) can be known with near certainty, other factors such as birth weight can only be estimated before delivery. Similarly, the response of an individual newborn to resuscitative efforts cannot be reliably predicted before birth. Published long-term follow-up outcome data reflect the response of the newborn to interventions that may no longer be in place, or may not reflect newer practices (for example, oscillator and nitric oxide ventilation therapy). Although the group consensus was that counseling and treatment should optimally be based on a more refined understanding of an individual infant’s likelihood of adverse outcomes, currently available predictive models using individual parameters are not known to be highly accurate. The development of accurate and precise predictive models based on ascertainable and accurate measures, which utilize updated and current outcome data, is an area of particular need.
Campbell DE, Fleischman AR . Limits of viability: dilemmas, decisions, and decision makers. Am J Perinatol 2001; 18: 117–128.
Perinatal care at the threshold of viability. ACOG Practice Bulletin No. 38. American College of Obstetricians and Gynecologists. Obstet Gynecol 2002; 100: 617–624.
MacDonald H American Academy of Pediatrics. Committee on Fetus and Newborn. Perinatal care at the threshold of viability. Pediatrics 2002; 110: 1024–1027.
Batton DG, Committee on Fetus and Newborn. Clinical report—antenatal counseling regarding resuscitation at an extremely low gestational age. Pediatrics 2009; 124: 422–427.
Pignotti MS . The definition of human viability: a historical perspective. Acta Paediatr 2010; 99: 33–36.
Khan RA, Burgoyne L, O’Connell MP, Dempsey EM . Resuscitation at the limits of viability—an Irish perspective. Acta Paediatr 2009; 98: 1456–1460.
Kollée LA, Cuttini M, Delmas D, Papiernik E, den Ouden AL, Agostino R et al. MOSAIC Research group. Obstetric interventions for babies born before 28 weeks of gestation in Europe: results of the MOSAIC study. BJOG 2009; 116: 1481–1491.
Zecca E, de Luca D, Costa S, Marras M, de Turris P, Romagnoli C . Delivery room strategies and outcomes in preterm infants with gestational age 24–28 weeks. J Matern Fetal Neonatal Med 2006; 19: 569–574.
Louis JM, Ehrenberg HM, Collin MF, Mercer BM . Perinatal intervention and neonatal outcomes near the limit of viability. Am J Obstet Gynecol 2004; 191: 1398–1402.
Verlato G, Gobber D, Drago D, Chiandetti L, Drigo P ; Working Group of Intensive Care in the Delivery Room of Extremely Premature Newborns. Guidelines for resuscitation in the delivery room of extremely preterm infants. J Child Neurol 2004; 19: 31–34.
Sanders MR, Donohue PK, Oberdorf MA, Rosenkrantz TS, Allen MC . Perceptions of the limit of viability: neonatologists’ attitudes toward extremely preterm infants. J Perinatol 1995; 15: 494–502.
Allen MC, Donohue PK, Dusman AE . The limit of viability—neonatal outcome of infants born at 22 to 25 weeks’ gestation. N Engl J Med 1993; 329: 1597–1601.
Andrews B, Lagatta J, Chu A, Plesha-Troyke S, Schreiber M, Lantos J et al. The nonimpact of gestational age on neurodevelopmental outcome for ventilated survivors born at 23–28 weeks of gestation. Acta Paediatr 2012; 101: 574–578.
Lau C, Ambalavanan N, Chakraborty H, Wingate MS, Carlo WA . Extremely low birth weight and infant mortality rates in the United States. Pediatrics 2013; 151: 855–860.
Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126: 443–456.
De Jesus LC, Pappas A, Shankaran S, Kendrick D, Das A, Higgins RD et al. Risk factors for post-neonatal intensive care unit discharge mortality among extremely low birth weight infants. J Pediatr 2012; 161: 70–74 e1–2.
Salihu HM, Emusu D, Aliyu ZY, Kirby RS, Alexander GR . Survival of ‘pre-viable’ infants in the United States. Wien Klin Wochenschr 2005; 117: 324–332.
Hoekstra RE, Ferrara TB, Couser RJ, Payne NR, Connett JE . Survival and long-term neurodevelopmental outcome of extremely premature infants born at 23–26 weeks’ gestational age at a tertiary center. Pediatrics 2004; 113: e1–e6.
Kamath BD, Box TL, Simpson M, Hernández JA . Infants born at the threshold of viability in relation to neonatal mortality: Colorado, 1991 to 2003. J Perinatol 2008; 28: 354–360.
Iams JD, Mercer BM ; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. What we have learned about antenatal prediction of neonatal morbidity and mortality. Semin Perinatol 2003; 27: 247–252.
Donohue PK, Boss RD, Shepard J, Graham E, Allen MC . Intervention at the border of viability: perspective over a decade. Arch Pediatr Adolesc Med 2009; 163: 902–906.
Morse SB, Wu SS, Ma C, Ariet M, Resnick M, Roth J . Racial and gender differences in the viability of extremely low birth weight infants: a population-based study. Pediatrics 2006; 117: e106–e112.
Mohamed MA, Nada A, Aly H . Day-by-day postnatal survival in very low birth weight infants. Pediatrics 2010; 126: e360–e366.
Petrova A, Mehta R, Anwar M, Hiatt M, Hegyi T . Impact of race and ethnicity on the outcome of preterm infants below 32 weeks gestation. J Perinatol 2003; 23: 404–408.
Tyson JE, Parikh NA, Langer J, Green C, Higgins RD, National Institute of Child Health and Human Development Neonatal Research Network. Intensive care for extreme prematurity—moving beyond gestational age. N Engl J Med 2008; 358: 1672–1681.
Batton B, Burnett C, Verhulst S, Batton D . Extremely preterm infant mortality rates and cesarean deliveries in the United States. Obstet Gynecol 2011; 118: 43–48.
Mehler K, Grimme J, Abele J, Huenseler C, Roth B, Kribs A . Outcome of extremely low gestational age newborns after introduction of a revised protocol to assist preterm infants in their transition to extrauterine life. Acta Paediatr 2012; 101: 1232–1239.
Kyser KL, Morriss FH Jr, Bell EF, Klein JM, Dagle JM . Improving survival of extremely preterm infants born between 22 and 25 weeks of gestation. Obstet Gynecol 2012; 119: 795–800.
Lee HC, Green C, Hintz SR, Tyson JE, Parikh NA, Langer J et al. Prediction of death for extremely premature infants in a population-based cohort. Pediatrics 2010; 126: e644–e650.
Smith PB, Ambalavanan N, Li L, Cotten CM, Laughon M, Walsh MC et al. Approach to infants born at 22 to 24 weeks’ gestation: relationship to outcomes of more-mature infants. Pediatrics 2012; 129: e1508–e1516.
Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR . EPICure Study Group Neurologic and developmental disability after extremely preterm birth. N Engl J Med 2000; 343: 378–384.
Marlow N, Wolke D, Bracewell MA, Samara M EPICure Study Group. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 2005; 352: 9–19.
Moore GP, Lemyre B, Barrowman N, Daboval T . Neurodevelopmental outcomes at 4 to 8 years of children born at 22 to 25 weeks’ gestational age. a meta-analysis. JAMA Pediatr 2013; 167: 967–974.
Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D . Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. The Cochrane Database of Systematic Reviews 2009 Issue 1. Art. No CD004661 doi:10.1002/14651858.CD004661.pub3.
Althuisius SM, Dekker GA, Hummel P, van Geijn HP, Cervical Incompetence Prevention Randomized Cerclage Trial. Cervical incompetence prevention randomized cerclage trial: emergency cerclage with bed rest versus bed rest alone. Am J Obstet Gynecol 2003; 189: 907–910.
Daskalakis G, Papantoniou N, Mesogitis S, Antsaklis A . Management of cervical insufficiency and bulging fetal membranes. Obstet Gynecol 2006; 107: 221–226.
Debby A, Sadan O, Glezerman M, Golan A . Favorable outcome following emergency second trimester cerclage. Int J Gynaecol Obstet 2007; 96: 16–19.
Stupin JH, David M, Siedentopf JP, Dudenhausen JW . Emergency cerclage versus bed rest for amniotic sac prolapse before 27 gestational weeks. A retrospective, comparative study of 161 women. Eur J Obstet Gynecol Reprod Biol 2008; 139: 32–37.
Gonzales LW, Ballard PL, Ertsey R, Williams MC . Glucocorticoids and thyroid hormones stimulate biochemical and morphological differentiation of human fetal lung in organ culture. J Clin Endocrinol Metab 1986; 62: 678–691.
Carlo WA, McDonald SA, Fanaroff AA, Vohr BR, Stoll BJ, Ehrenkranz RA et al. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks’ gestation. JAMA 2011; 306: 2348–2358.
Mori R, Kusuda S, Fujimura M, Neonatal Research Network Japan. Antenatal corticosteroids promote survival of extremely preterm infants born at 22 to 23 weeks of gestation. J Pediatr 2011; 159 (110–14): e1.
Chawla S, Natarajan G, Rane S, Thomas R, Cortez J, Lua J . Outcomes of extremely low birth weight infants with varying doses and intervals of antenatal steroid exposure. J Perinat Med 2010; 38: 419–423.
Chawla S, Bapat R, Pappas A, Bara R, Zidan M, Natarajan G . Neurodevelopmental outcome of extremely premature infants exposed to incomplete, no or complete antenatal steroids. J Matern Fetal Neonatal Med 2013; 26: 1542–1547.
Costantine MM, Weiner SJ Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet Gynecol 2009; 114: 354–364.
Alfirevic Z, Milan SJ, Livio S . Caesarean section versus vaginal delivery for preterm birth in singletons. The Cochrane Database of Systematic Reviews 2013 Issue 9. Art CD000078. doi:10.1002/14651858.cd000078.pub3.
Lee HC, Gould JB . Survival rates and mode of delivery for vertex preterm neonates according to small- or appropriate-for-gestational-age status. Pediatrics 2006; 118: e1836–e1844.
Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES . Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 2012; 345: e7976.
Wylie BJ, Davidson LL, Batra M, Reed SD . Method of delivery and neonatal outcome in very low-birthweight vertex-presenting fetuses. Am J Obstet Gynecol 2008; 198 (640): e1–e7.
Reddy UM, Zhang J, Sun L, Chen Z, Raju TN, Laughon SK . Neonatal mortality by attempted route of delivery in early preterm birth. Am J Obstet Gynecol 2012; 207 (117): e1–e8.
Chervenak FA, McCullough LB, Levene MI . An ethically justified, clinically comprehensive approach to peri-viability: gynaecological, obstetric, perinatal and neonatal dimensions. J Obstet Gynaecol 2007; 27: 3–7.
Perlman JM, Wyllie J, Kattwinkel J, Atkins DL, Chameides L, Goldsmith JP et al. Part 11: neonatal resuscitation: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2010; 122: S516–S538.
Wyckoff MH, Salhab WA, Heyne RJ, Kendrick DE, Stoll BJ, Laptook AR, National Institute of Child Health and Human Development Neonatal Research Network. Outcome of extremely low birth weight infants who received delivery room cardiopulmonary resuscitation. J Pediatr 2012; 160 (239–44): e2.
Laptook AR, Salhab W, Bhaskar B Neonatal Research Network. Admission temperature of low birth weight infants: predictors and associated morbidities. Pediatrics 2007; 119: e643–e649.
World Health Organization, Maternal and Newborn Health/Safe Motherhood. Thermal Protection of the Newborn: a Practical Guide . World Health Organization: Geneva, Switzerland, 1997.
Been JV, Degraeuwe PL, Kramer BW, Zimmermann LJ . Antenatal steroids and neonatal outcome after chorioamnionitis: a meta-analysis. BJOG 2011; 118: 113–122.
Eriksson L, Haglund B, Ewald U, Odlind V, Kieler H . Short and long-term effects of antenatal corticosteroids assessed in a cohort of 7827 children born preterm. Acta Obstet Gynecol Scand 2009; 88: 933–938.
Abbasi S, Oxford C, Gerdes J, Sehdev H, Ludmir J . Antenatal corticosteroids prior to 24 weeks’ gestation and neonatal outcome of extremely low birth weight infants. Am J Perinatol 2010; 27: 61–66.
Fowlie PW, Davis PG, McGuire W . Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. The Cochrane Database of Systematic Reviews 2010 Issue 7. Art No. CD000174. doi:10.1002/14651858.CD000174.pub2.
Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344: 1966–1972.
Janvier A, Lorenz JM, Lantos JD . Antenatal counselling for parents facing an extremely preterm birth: limitations of the medical evidence. Acta Paediatr 2012; 101: 800–804.
The authors declare no conflict of interest.
This is an executive summary of a Society for Maternal-Fetal Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologists and American Academy of Pediatricians Workshop that was held 12–13 February 2013 in San Francisco, CA, USA. This article is being published concurrently in the May 2014 issue (vol. 123, no. 5) of Obstetrics & Gynecology and the May 2014 issue (vol. 210, no. 5) of the American Journal of Obstetrics and Gynecology.
The information and guidance herein reflect consensus regarding clinical and scientific advances as of the Workshop, is subject to change, and should not be construed as dictating an exclusive course of treatment or procedure. The information and guidance provided does not necessarily represent the official views of the National Institutes of Health, Society for Maternal-Fetal Medicine, National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, or the American Academy of Pediatricians, or the views of each individual participant in the Workshop. For a list of organizers, invited speakers, and discussants who participated in the workshop, see the Appendix online at http://links.lww.com/AOG/A483.
About this article
Cite this article
Raju, T., Mercer, B., Burchfield, D. et al. Periviable birth: executive summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. J Perinatol 34, 333–342 (2014). https://doi.org/10.1038/jp.2014.70
Early antenatal counseling in the outpatient setting for high-risk pregnancies: a randomized control trial
Journal of Perinatology (2021)
Improved Survival of Periviable Infants after Alteration of the Threshold of Viability by the Neonatal Resuscitation Program 2015
Maternal metabolic profiling to assess fetal gestational age and predict preterm delivery: a two-centre retrospective cohort study in the US
BMJ Open (2020)
Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction
American Journal of Obstetrics and Gynecology (2020)
Advances in Neonatal Care (2020)