Society for Maternal-Fetal Medicine Consult Series #71: Management of previable and periviable preterm prelabor rupture of membranes.

Previable and periviable preterm prelabor rupture of membranes are challenging obstetrical complications to manage given the substantial risk of maternal morbidity and mortality, with no guarantee of fetal benefit. The following are the Society for Maternal-Fetal Medicine recommendations for the management of previable and periviable preterm prelabor rupture of membranes before the period when a trial of neonatal resuscitation and intensive care would be considered appropriate by the healthcare team and desired by the patient: (1) we recommend that pregnant patients with previable and periviable preterm prelabor rupture of membranes receive individualized counseling about the maternal and fetal risks and benefits of both abortion care and expectant management to guide an informed decision; all patients with previable and periviable preterm prelabor rupture of membranes should be offered abortion care, and expectant management can also be offered in the absence of contraindications (GRADE 1C); (2) we recommend antibiotics for pregnant individuals who choose expectant management after preterm prelabor rupture of membranes at ≥24 0/7 weeks of gestation (GRADE 1B); (3) antibiotics can be considered after preterm prelabor rupture of membranes at 20 0/7 to 23 6/7 weeks of gestation (GRADE 2C); (4) administration of antenatal corticosteroids and magnesium sulfate is not recommended until the time when a trial of neonatal resuscitation and intensive care would be considered appropriate by the healthcare team and desired by the patient (GRADE 1B); (5) serial amnioinfusions and amniopatch are considered investigational and should be used only in a clinical trial setting; they are not recommended for routine care of previable and periviable preterm prelabor rupture of membranes (GRADE 1B); (6) cerclage management after previable or periviable preterm prelabor rupture of membranes is similar to cerclage management after preterm prelabor rupture of membranes at later gestational ages; it is reasonable to either remove the cerclage or leave it in situ after discussing the risks and benefits and incorporating shared decision-making (GRADE 2C); and (7) in subsequent pregnancies after a history of previable or periviable preterm prelabor rupture of membranes, we recommend following guidelines for management of pregnant persons with a previous spontaneous preterm birth (GRADE 1C).

The importance of professional responsibility and fetal viability in the management of abortion.

In June 2022, the Dobbs v. Jackson Women's Health Organization Supreme Court decision ended the constitutional right to the professional practice of abortion throughout the United States. The removal of the constitutional right to abortion has significantly altered the practice of obstetricians and gynecologists across the US. It potentially increases risks to pregnant patients, leads to profound changes in how physicians can provide care, especially in states with strict bans or gestational limits to abortion, and has introduced personal challenges, including moral distress and injury as well as legal risks for patients and clinicians alike. The professional responsibility model is based on the ethical concept of medicine as a profession and has been influential in shaping medical ethics in the field of obstetrics and gynecology. It provides the framework for the importance of ethical and professional conduct in obstetrics and gynecology. Viability marks a stage where the fetus is a patient with a claim to access to medical care. By allowing unrestricted abortions past this stage without adequate justifications, such as those concerning the life and health of the pregnant individual, or in instances of serious fetal anomalies, the states may not be upholding the equitable ethical consideration owed to the fetus as a patient. Using the professional responsibility model, we emphasize the need for nuanced, evidence-based policies that allow abortion management prior to viability without restrictions and allow abortion after viability to protect the pregnant patient's life and health, as well as permitting abortion for serious fetal anomalies.

"It feels like you have to choose one or the other": a qualitative analysis of obstetrician focus groups on periviability counseling.

OBJECTIVES: The objective of this study was to gain knowledge and ascertain challenges about periviability counseling among obstetricians to inform curricular development. METHODS: Focus groups were utilized. A series of open-ended questions was posed to each group of obstetricians; responses were audio recorded and transcribed. Transcriptions were analyzed by two coders using thematic analysis. RESULTS: Four focus groups were convened. Prominent themes included: (1) Obstetrician knowledge about neonatal outcomes is limited, (2) Periviability counseling is both time intensive and time-challenged, (3) Patient processing of information relies on the content, delivery and patient readiness, and (4) Obstetrician bias is toward advocating for maternal safety, which may run counter to parental instinct to "do everything." The last theme was specifically focused on the role of cesarean delivery. CONCLUSIONS: Curricula focused on improving obstetrician periviability counseling should focus on neonatal outcomes, the role of cesarean delivery, and utilization of shared decision-making.

Effectiveness and adverse effects of vaginal misoprostol as a single agent for second trimester pregnancy termination: the impact of fetal viability.

PURPOSE: To compare the effectiveness of vaginal misoprostol for second-trimester termination between pregnancies with a dead fetus in utero and those with a live fetus and to identify factors associated with the success rate. METHODS: Singleton pregnancies with live fetuses and dead fetuses, between 14 and 28 weeks of gestation, with an unfavorable cervix, were recruited to have pregnancy termination with intravaginal misoprostol 400 mcg every 6 h. RESULTS: Misoprostol was highly effective for termination, with a low failure rate of 6.3%. The effectiveness was significantly higher in pregnancies with a dead fetus (log-rank test; p: 0.008), with a median delivery time of 11.2 vs. 16.7 h. Fetal viability, fetal weight or gestational age, and an initial Bishop score were significantly associated with the total amount of misoprostol dosage used for induction. Fetal viability and gestational age/fetal weight were still independent factors after adjustment for other co-factors on multivariate analysis. CONCLUSION: Vaginal misoprostol is highly effective for second-trimester termination, with significantly higher effectiveness in pregnancies with a dead fetus. Also, the effectiveness is significantly associated with birth weight/gestational age, and initial Bishop score.

Orphans cannot be after-birth aborted: a response to Bobier.

I offer a response to an objection to my account of the moral difference between fetuses and newborns, an account that seeks to address an analogy between abortion and infanticide, which is based on the apparent equality of moral value of fetuses and newborns.

The (mis)use of fetal viability as the determinant of non-criminal abortion in the Netherlands and England and Wales.

Time plays a fundamental role in abortion regulation. In this article, we compare the regulatory frameworks in England and Wales and the Netherlands as examples of the centrality accorded to viability in the determination of the parameters of non-criminal abortion, demonstrating that the use of viability as a threshold renders the law uncertain. We assess the role played by the concept of viability, analysing its impact upon the continued criminalization of abortion and categorization of abortion as a medical matter, rather than a reproductive choice. We conclude that viability is misconceived in its application to abortion and that neonatal viability (relating to treatment of the premature infant) and fetal viability (related to the capacity to survive birth) must be distinguished to better reflect the social context within which the law and practice of abortion operate. We show how viability thresholds endanger pregnant people.

Proteome-defined changes in cellular pathways for decidua and trophoblast tissues associated with location and viability of early-stage pregnancy.

BACKGROUND: In early pregnancy, differentiating between a normal intrauterine pregnancy (IUP) and abnormal gestations including early pregnancy loss (EPL) or ectopic pregnancy (EP) is a major clinical challenge when ultrasound is not yet diagnostic. Clinical treatments for these outcomes are drastically different making early, accurate diagnosis imperative. Hence, a greater understanding of the biological mechanisms involved in these early pregnancy complications could lead to new molecular diagnostics. METHODS: Trophoblast and endometrial tissue was collected from consenting women having an IUP (n = 4), EPL (n = 4), or EP (n = 2). Samples were analyzed by LC-MS/MS followed by a label-free proteomics analysis in an exploratory study. For each tissue type, pairwise comparisons of different pregnancy outcomes (EPL vs. IUP and EP vs. IUP) were performed, and protein changes having a fold change ≥ 3 and a Student's t-test p-value ≤ 0.05 were defined as significant. Pathway and network classification tools were used to group significantly changing proteins based on their functional similarities. RESULTS: A total of 4792 and 4757 proteins were identified in decidua and trophoblast proteomes. For decidua, 125 protein levels (2.6% of the proteome) were significantly different between EP and IUP, whereas EPL and IUP decidua were more similar with only 68 (1.4%) differences. For trophoblasts, there were 66 (1.4%) differences between EPL and IUP. However, the largest group of 344 differences (7.2%) was observed between EP and IUP trophoblasts. In both tissues, proteins associated with ECM remodeling, cell adhesion and metabolic pathways showed decreases in EP specimens compared with IUP and EPL. In trophoblasts, EP showed elevation of inflammatory and immune response pathways. CONCLUSIONS: Overall, differences between an EP and IUP are greater than the changes observed when comparing ongoing IUP and nonviable intrauterine pregnancies (EPL) in both decidua and trophoblast proteomes. Furthermore, differences between EP and IUP were much higher in the trophoblast than in the decidua. This observation is true for the total number of protein changes as well as the extent of changes in upstream regulators and related pathways. This suggests that biomarkers and mechanisms of trophoblast function may be the best predictors of early pregnancy location and viability.

Does birth matter?

This paper is a response to a recent paper by Bobier and Omelianchuk in which they argue that the critics of Giubilini and Minerva's defence of infanticide fail to adequately justify a moral difference at birth. They argue that such arguments would lead to an intuitively less plausible position: that late-term abortions are permissible, thus creating a dilemma for those who seek to argue that birth matters. I argue that the only way to resolve this dilemma, is to bite the naturalist bullet and accept that the intuitively plausible idea that birth constitutes a morally relevant event is simply mistaken and biologically misinformed.

Why appeals to the moral significance of birth are saddled with a dilemma.

In 'Dilemma for Appeals to the Moral Significance of Birth', we argued that a dilemma is faced by those who believe that birth is the event at which infanticide is ruled out. Those who reject the moral permissibility of infanticide by appeal to the moral significance of birth must either accept the moral permissibility of a late-term abortion for a non-therapeutic reason or not. If they accept it, they need to account for the strong intuition that her decision is wrong as well as deny the underlying normative principle that killing a viable fetus requires good reason, and not wanting to care for the child when the child could be easily placed for adoption is not a good enough reason to abort. If they reject the moral permissibility of the late-term abortion, they need to explain why her decision is wrong. Doing so, however, will undermine their own project of denying infanticide by appeal to birth. Walter Veit argues that the dilemma relies too much on intuition and does not live up to biological continuity. We explain why his criticisms are unconvincing.

Trends in Active Treatment of Live-born Neonates Between 22 Weeks 0 Days and 25 Weeks 6 Days by Gestational Age and Maternal Race and Ethnicity in the US, 2014 to 2020.

Importance: Birth in the periviable period between 22 weeks 0 days and 25 weeks 6 days' gestation is a major source of neonatal morbidity and mortality, and the decision to initiate active life-saving treatment is challenging. Objective: To assess whether the frequency of active treatment among live-born neonates in the periviable period has changed over time and whether active treatment differed by gestational age at birth and race and ethnicity. Design, Setting, and Participants: Serial cross-sectional descriptive study using National Center for Health Statistics natality data from 2014 to 2020 for 61 908 singleton live births without clinical anomalies between 22 weeks 0 days and 25 weeks 6 days in the US. Exposures: Year of delivery, gestational age at birth, and race and ethnicity of the pregnant individual, stratified as non-Hispanic Asian/Pacific Islander, non-Hispanic Black, Hispanic/Latina, and non-Hispanic White. Main Outcomes and Measures: Active treatment, determined by whether there was an attempt to treat the neonate and defined as a composite of surfactant therapy, immediate assisted ventilation at birth, assisted ventilation more than 6 hours in duration, and/or antibiotic therapy. Frequencies, mean annual percent change (APC), and adjusted risk ratios (aRRs) were estimated. Results: Of 26 986 716 live births, 61 908 (0.2%) were periviable live births included in this study: 5% were Asian/Pacific Islander, 37% Black, 24% Hispanic, and 34% White; and 14% were born at 22 weeks, 21% at 23 weeks, 30% at 24 weeks, and 34% at 25 weeks. Fifty-two percent of neonates received active treatment. From 2014 to 2020, the overall frequency (mean APC per year) of active treatment increased significantly (3.9% [95% CI, 3.0% to 4.9%]), as well as among all racial and ethnic subgroups (Asian/Pacific Islander: 3.4% [95% CI, 0.8% to 6.0%]); Black: 4.7% [95% CI, 3.4% to 5.9%]; Hispanic: 4.7% [95% CI, 3.4% to 5.9%]; and White: 3.1% [95% CI, 1.1% to 4.4%]) and among each gestational age range (22 weeks: 14.4% [95% CI, 11.1% to 17.7%] and 25 weeks: 2.9% [95% CI, 1.5% to 4.2%]). Compared with neonates born to White individuals (57.0%), neonates born to Asian/Pacific Islander (46.2%; risk difference [RD], -10.81 [95% CI, -12.75 to -8.88]; aRR, 0.82 [95% CI, [0.79-0.86]), Black (51.6%; RD, -5.42 [95% CI, -6.36 to -4.50]; aRR, 0.90 [95% CI, 0.89 to 0.92]), and Hispanic (48.0%; RD, -9.03 [95% CI, -10.07 to -7.99]; aRR, 0.83 [95% CI, 0.81 to 0.85]) individuals were significantly less likely to receive active treatment. Conclusions and Relevance: From 2014 to 2020 in the US, the frequency of active treatment among neonates born alive between 22 weeks 0 days and 25 weeks 6 days significantly increased, and there were differences in rates of active treatment by race and ethnicity.

Information Order for Periviable Counseling: Does It Make a Difference?

OBJECTIVES: To examine whether the order of presenting survival vs disability information, with or without the description of infant neonatal intensive care unit (NICU) experiences would influence treatment choice during hypothetical periviable birth counseling. STUDY DESIGN: An internet sample of childbearing-aged women (n = 839) viewed a pictograph displaying the chances of survival and a pictograph on the chances of disability for a baby resuscitated during the periviable period. The sample was randomized to the order of pictographs and level of description of infant NICU experiences. Participants selected between intensive care or comfort care and reported their personal values. RESULTS: The order of the information influenced treatment choices (P = .02); participants were more likely to choose intensive care if they saw the survival pictograph first (70%) than the disability pictograph first (62%). Level of description of premature infant NICU experiences did not influence treatment choice (P = .92). Participants who valued sanctity of life, autonomy in making decisions, who were more religious, and had adequate health literacy were more likely to choose intensive care. Such participant characteristics had greater explanatory power than the experimental manipulations. CONCLUSIONS: Subtle differences in how information is presented may influence critical decisions. However, even among women with the same values, diversity in treatment choice remains.

Proactive neonatal treatment at 22 weeks of gestation: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to provide a systematic review and meta-analysis to quantify prognosis and identify factors associated with variations in reported mortality estimates among infants who were born at 22 weeks of gestation and provided proactive treatment (resuscitation and intensive care). DATA SOURCES: PubMed, Scopus, and Web of Science databases, with no language restrictions, were searched for articles published from January 2000 to February 2020. STUDY ELIGIBILITY CRITERIA: Reports on live-born infants who were delivered at 22 weeks of gestation and provided proactive care were included. The primary outcome was survival to hospital discharge; secondary outcomes included survival without major morbidity and survival without neurodevelopmental impairment. Because we expected differences across studies in the definitions for various morbidities, multiple definitions for composite outcomes of major morbidities were prespecified. Neurodevelopmental impairment was based on Bayley Scales of Infant Development II or III. Data extractions were performed independently, and outcomes agreed on a priori. STUDY APPRAISAL AND SYNTHESIS METHODS: Methodological quality was assessed using the Quality in Prognostic Studies tool. An adapted version of the Grading of Recommendations Assessment, Development and Evaluation approach for prognostic studies was used to evaluate confidence in overall estimates. Outcomes were assessed as prevalence and 95% confidence intervals. Variabilities across studies attributable to heterogeneity were estimated with the I2 statistic; publication bias was assessed with the Luis Furuya-Kanamori index. Data were pooled using the inverse variance heterogeneity model. RESULTS: Literature searches returned 21,952 articles, with 2034 considered in full; 31 studies of 2226 infants who were delivered at 22 weeks of gestation and provided proactive neonatal treatment were included. No articles were excluded for study design or risk of bias. The pooled prevalence of survival was 29.0% (95% confidence interval, 17.2-41.6; 31 studies, 2226 infants; I2=79.4%; Luis Furuya-Kanamori index=0.04). Survival among infants born to mothers receiving antenatal corticosteroids was twice the survival of infants born to mothers not receiving antenatal corticosteroids (39.0% vs 19.5%; P<.01). The overall prevalence of survival without major morbidity, using a definition that includes any bronchopulmonary dysplasia, was 11.0% (95% confidence interval, 8.0-14.3; 10 studies, 374 infants; I2=0%; Luis Furuya-Kanamori index=3.02). The overall rate of survival without moderate or severe impairment was 37.0% (95% confidence interval, 14.6-61.5; 5 studies, 39 infants; I2=45%; Luis Furuya-Kanamori index=-0.15). Based on the year of publication, survival rates increased between 2000 and 2020 (slope of the regression line=0.09; standard error=0.03; P<.01). Studies were highly diverse with regard to interventions and outcomes reported. CONCLUSION: The reported survival rates varied greatly among studies and were likely influenced by combining observational data from disparate sources, lack of individual patient-level data, and bias in the component studies from which the data were drawn. Therefore, pooled results should be interpreted with caution. To answer fundamental questions beyond the breadth of available data, multicenter, multidisciplinary collaborations, including alignment of important outcomes by stakeholders, are needed.

Abortion Rights after Artificial Wombs: Why Decriminalisation is Needed Ahead of Ectogenesis.

Significant scientific progress has been made toward artificial womb technology, which would allow part of human gestation to occur outside the body. Bioethical and legal scholars have argued that artificial wombs will challenge defences of abortion based in arguments for protecting bodily autonomy, for a pregnant person could have the foetus transferred to an artificial womb instead of being terminated. Drawing on examples from the common law jurisdictions of Canada, the USA, and the UK, I assess three ways scholars have argued abortion might be defended after ectogenesis (through redefining foetal viability, through a property right, and through a right to avoid genetic parenthood). I argue that while each of these proposals has strategic merit, each has significant legal and ethical limitations. Taking the normative position that abortion will remain a vital healthcare resource, I make the case for protecting abortion rights from a challenge posed by ectogenesis by focusing on decriminalisation.

Early embryo-maternal communication in the oviduct: A review.

An intact embryo-maternal communication is critical for the establishment of a successful pregnancy. To date, a huge number of studies have been performed describing the complex process of embryo-maternal signaling within the uterus. However, recent studies indicate that the early embryo communicates with the oviductal cells shortly after fertilizationand that this is important for the successful establishment of pregnancy. Only if the early embryo is capable to signal the mother within a precise timeframe and to garner a response, will the embryo be able to survive and reach the uterus. This review will give an overview of all the experimental designs which have investigated embryo-maternal interaction in the oviduct. In addition to that, it will provide a comprehensive analysis of the findings to date elucidating the morphological and molecular changes in the oviduct which are induced by the presence of the early embryo highlighting how the tubal responses affect embryo development and survival.

Fecundity is impaired in a mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI), or brittle bone disease, is most often caused by mutations in genes encoding type I collagen or proteins that process it. Women with OI have a small, but significant increase in risk of serious pregnancy complications including uterine rupture. Here, the OI mouse, Col1a2oim/oim , was used to examine the effects of collagen mutation on establishment and maintenance of pregnancy. Picrosirius birefringence was faint in Col1a2oim/oim uteri, indicating diminished collagen in the myometrium and endometrium. There was some evidence of increased uterine gland number (p = .055) and size (p = .12) in (p = .055) virgin uteri, though the they were not significantly different than controls. There were no differences in the number of corpora lutea, or the time from pairing to delivery of pups between Col1a2oim/oim and control dams, suggesting that ovulation and conception occur normally. However, when examined at Gestation Day 6.5 (postimplantation), gestation Day 10.5 (midpregnancy), and Postnatal Days 1-2, Col1a2oim/oim dams had significantly fewer viable pups than controls overall. In pairwise comparisons, the loss was only significant in the postnatal group, suggesting the gradual loss of pups over time. Overall, the Col1a2oim/oim mouse data suggest that OI impairs uterine function in pregnancy in a way that affects a small but significant number of fetuses.

Hypoxanthine phosphoribosyltransferase (HPRT)-deficiency is associated with impaired fertility in the female rat.

The purine hypoxanthine plays important role in regulating oocyte maturation and early embryonic development. The enzyme hypoxanthine phosphoribosyltransferase (HPRT) recycles hypoxanthine to generate substrates for nucleotide synthesis and key metabolites, and here we show that HPRT deficiency in the rat disrupts early embryonic development and causes infertility in females.

Values clarification: Eliciting the values that inform and influence parents' treatment decisions for periviable birth.

BACKGROUND: Values clarification can assist families facing the threat of periviable delivery in navigating the complexity of competing values related to death, disability, and quality of life (QOL). OBJECTIVE: We piloted values clarification exercises to inform resuscitation decision making and qualitatively assess perceptions of QOL. METHODS: We conducted a mixed-method study of women with threatened periviable delivery (22 0/7-24 6/7 weeks) and their important others (IOs). Participants engaged in three values clarification activities as part of a semi-structured interview-(a) Card sorting nine conditions as an acceptable/unacceptable QOL for a child; (b) Rating/ranking seven common concerns in periviable decision making (scale 0-10, not at all to extremely important); and (c) "Agreed/disagreed" with six statements regarding end-of-life treatment, disability, and QOL. Participants were also asked to define "QOL" and describe their perceptions of a good and poor QOL for their child. Analysis was conducted using SAS version 9.4 and NVivo 12. RESULTS: All mild disabilities were an acceptable QOL, while two-thirds of participants considered long-term mechanical ventilation unacceptable. Although pregnant women rated "Impact on Your Physical/Mental Health" (average 5.6) and IOs rated "Financial Concerns" the highest (average 6.6), both groups ranked "Financial Concerns" as the most important concern (median 5.0 and 6.0, respectively). Most participants agreed that "Any amount of life is better than no life at all" (pregnant women 62.1%; IOs 75.0%) and disagreed that resuscitation would cause "Too much suffering" for their child (pregnant women 71.4%; IOs 80.0%). Half were familiar with the phrase "QOL". Although the majority described a good QOL in terms of emotional well-being (eg "loved", "happy", "supported"), a poor QOL was described in terms of functionality (eg "dependent" and "confined"). Additionally, financial stability emerged as a distinctive theme when IOs discussed poor QOL. CONCLUSION: The study offers important insights on parental perspectives in periviable decision making and potential values clarification tools for decision support.

Ectogestation ethics: The implications of artificially extending gestation for viability, newborn resuscitation and abortion.

Recent animal research suggests that it may soon be possible to support the human fetus in an artificial uterine environment for part of a pregnancy. A technique of extending gestation in this way ("ectogestation") could be offered to parents of extremely premature infants (EPIs) to improve outcomes for their child. The use of artificial uteruses for ectogestation could generate ethical questions because of the technology's potential impact on the point of "viability"-loosely defined as the stage of pregnancy beyond which the fetus may survive external to the womb. Several medical decisions during the perinatal period are based on the gestation at which infants are considered viable, for example decisions about newborn resuscitation and abortion, and ectogestation has the potential to impact on these. Despite these possible implications, there is little existing evidence or analysis of how this technology would affect medical practice. In this paper, we combine empirical data with ethical analysis. We report a survey of 91 practicing Australian obstetricians and neonatologists; we aimed to assess their conceptual understanding of "viability," and what ethical consequences they envisage arising from improved survival of EPIs. We also assess what the ethical implications of extending gestation should be for newborn and obstetric care. We analyze the concept of viability and argue that while ectogestation might have implications for the permissibility of neonatal life-prolonging treatment at extremely early gestation, it should not necessarily have implications for abortion policy. We compare our ethical findings with the results of the survey.

An alternative approach to developing guidelines for the management of an anticipated extremely preterm infant.

Objectives To identify the probability of survival and severe neurodevelopmental impairment (sNDI) at which perinatal physicians would or would not offer or recommend resuscitation at birth for extremely preterm infants. Methods A Delphi process consisting of five rounds was implemented to seek consensus (>80% agreement) amongst British Columbia perinatal physicians. The first-round consisted of neonatal and maternal-fetal-medicine Focus Groups. Rounds two to five surveyed perinatal physicians, building upon previous rounds. Draft guidelines were developed and agreement sought. Results Based on 401 responses across all rounds, consensus was obtained that resuscitation should not be offered if survival probability <5%, not recommended if survival probability 5 to <10%, resuscitation recommended if survival without sNDI probability >70 to 90% and resuscitation standard care if survival without sNDI >90%. Conclusions This physician consensus-based, objective framework for the management of an anticipated extremely preterm infant is a transparent alternative to existing guidelines, minimizing gestational-ageism and allowing for individualized management utilizing up-to-date data. Further input from other key stakeholders will be required prior to guideline implementation.