Preeclampsia: The Need for a Biological Definition and Diagnosis.

The centuries-old approach to the prevention of eclampsia and its associated maternal morbidity and mortality is based on the recognition of the presence of premonitory signs and symptoms such as hypertension and proteinuria. The spectrum of preceding signs and symptoms came to be known as preeclampsia, which is debatably considered to be an early stage on a clinical continuum possibly leading to eclampsia. The premonitory signs and symptoms were then construed as diagnostic criteria for the poorly understood syndrome of preeclampsia, and this led to a perpetual debate that remains subject to wide disagreement and periodic updates. In this commentary, we will draw attention to the fact that the criteria for preeclampsia should be viewed from the prism of a screening test rather than as diagnostic of a condition in itself. Focusing research on developing better diagnostic and screening methods for what is clinically important, namely maternal and perinatal morbidity and mortality from hypertensive disorders of pregnancy, a long overdue upgrade from what was possible centuries ago, will ultimately lead to better management approaches to what really matters.

Cross-cultural barriers to health care.

Culturally sensitive health care represents a real ethical and practical need in a Western healthcare system increasingly serving a multiethnic society. This review focuses on cross-cultural barriers to health care and incongruent aspects from a cultural perspective in the provision of health care. To overcome difficulties in culturally dissimilar interactions and eventually remove cross-cultural barriers to health care, a culturally sensitive physician considers his or her own identity, values, and beliefs; recognizes the similarities and differences among cultures; understands what those similarities and differences mean; and is able to bridge the differences to accomplish clear and effective communication.

The Ethics and Practice of Periviability Care.

Since the 1960s, the gestational age at which premature infants typically survive has decreased by approximately one week per decade [...].

The ethics and practice of perinatal care at the limit of viability: FIGO recommendations.

An arbitrary gestational age limit of viability cannot be set, and in clinical practice the focus should be on a periviability interval-the so-called "gray zone" of prognostic uncertainty. For cases within this interval, the most appropriate decision-making process remains debatable and periviability has emerged as one of the greatest challenges in bioethics. Universally recognized ethical principles may be interpreted differently due to socioeconomic, cultural, and religious aspects. In the case of periviability, there is considerable uncertainty over whether interventions result in a greater balance of clinical good over harm. Furthermore, the fetus or neonate is unable to exercise autonomy and the physicians and parents will act as patient surrogates. When parents and physicians disagree about the infant's best interest, a dialogue without paternalistic attitudes is essential, whereby physicians should only offer, but not recommend, perinatal interventions. Parental choice, based on thorough information, should be respected within the limits of what is medically feasible and appropriate. When disagreements between parents and physicians occur, how is consensus to be achieved? Professional guidelines can be helpful as a framework and starting point for discussion. In reality, however, guidelines only rarely draw categorical lines and in many cases remain vague and ambiguously worded. Local ethics committees can provide counseling and function as moderators during discussions, but ethics committees do not have decision precedence. Counseling assumes the most significant role in periviability discussions, taking into consideration the particular fetal and maternal characteristics, as well as parental values. Several caveats should be observed relative to counseling: message fragmentation or inconsistence should be minimized, prognosis should preferably be presented in a positive framing, and overreliance on statistics should be avoided. It is recommended that decisions regarding neonatal resuscitation in the periviability interval be made before birth and not conditional on the newborn's appearance at birth. Regardless of decision, it is important to assure pre- and postnatal coherence. The present article describes how individual physicians, centers, and countries differ in the approach to the decision to initiate or forgo intensive care in the periviability interval. It is impossible to provide a global consensus view and there can be no unifying ethical, moral, or practical strategy. Nevertheless, ethically justified, quality care comprises early involvement of the obstetric and neonatal team to enable a coherent, comprehensible, nonpaternalistic, and balanced plan of care. Ultimately, physicians will need to adjust the expectations to the local standards, local outcome data, and local neonatal support availability.

Is thrombin activation predictive of subsequent preterm delivery?

OBJECTIVE: To determine the relation between thrombin generation (measured by thrombin-antithrombin [TAT] complexes) early in pregnancy and subsequent preterm delivery. STUDY DESIGN: Select cohort of 731 women undergoing indicated second trimester amniocentesis prospectively followed to delivery. Primary outcome was preterm delivery. TAT levels were examined continuously and categorized by quartiles. Multivariable techniques were applied to adjust for potential confounders. Receiver operating characteristic curve analysis was used to determine a discriminatory cutoff level for TAT complexes. RESULTS: TAT concentration was significantly higher in women who delivered preterm (median, 98.9 mcg/L) than in those who did not (median, 66.3 mcg/L; P < .001). This difference persisted when 55 spontaneous preterm deliveries (median, 87.6 mcg/L) and 34 indicated preterm deliveries (median, 117.7 mcg/L) were separately compared with controls (P = .04 and P < .001, respectively). Crude and adjusted odds ratio for preterm delivery in the upper 2 TAT quartiles relative to the uppermost quartile relative to the lowest quartile were 2.45 (95% confidence interval [CI], 1.36-4.72; P = .004) and 2.31 (95% CI, 1.18-4.65; P = .017), respectively. Despite these distinct differences, the area under the receiver operating characteristic curve was only 0.62 (95% CI, 0.56-0.69), indicating poor performance of TAT concentration as a risk discriminator. CONCLUSION: Amniotic fluid levels of TAT complexes in the second trimester are elevated in women who subsequently deliver preterm, suggesting that thrombin generation may be involved in the various etiopathogenic mechanisms leading to preterm delivery.

The diagnosis of rupture of fetal membranes (ROM): a meta-analysis.

AIM: The aim of this study was to compare the performance of tests based on the detection of insulin-like growth factor binding protein 1 (IGFBP-1) and placental α-microglobulin-1 (PAMG-1) in diagnosing rupture of fetal membranes (ROM) across different patient populations. METHODS: A meta-analysis was conducted on prospective observational or cohort studies investigating ROM tests based on the detection of IGFBP-1 and PAMG-1 meeting the following criteria: (1) performance metrics calculated by comparing results to an adequate reference method; (2) sensitivity thresholds of the investigated tests matching those of the currently available tests; (3) study population, as a minimum, included patients between 25 and 37 weeks of gestation. Sensitivities, specificities, and diagnostic odds ratios were calculated. RESULTS: Across all patient populations, the analyzed performance measures of the PAMG-1 test were significantly superior compared with those of the IGFBP-1 test. Of particular clinical relevance, PAMG-1 outperformed IGFBP-1 in the equivocal group, which comprised patients with uncertain rupture of membranes (sensitivity, 96.0% vs. 73.9%; specificity, 98.9% vs. 77.8%; PAMG-1 vs. IGFBP-1 tests, respectively). CONCLUSIONS: Compared with its performance in women with known membrane status, the accuracy of the IGFBP-1 test decreases significantly when used on patients whose membrane status is unknown. In this latter clinically relevant population, the PAMG-1 test has higher accuracy than the IGFBP-1 test.

Prospective investigation of second-trimester thrombin activation and preterm birth.

OBJECTIVE: We sought to determine if second-trimester amniotic fluid thrombin-antithrombin (TAT) complexes concentration correlates with subsequent preterm birth. STUDY DESIGN: A cohort of 550 women with singleton nonanomalous pregnancies undergoing second-trimester genetic amniocentesis was followed up to delivery and analyzed as a nested case-control study. Cases of preterm birth (n = 52) were compared with 104 term control subjects. Amniotic fluid collected at amniocentesis was tested for TAT. RESULTS: TAT concentrations were significantly higher in women who delivered preterm (median 115.9 µg/L) than in those who did not (median 62.2 µg/L; P < .001). This difference persisted when 31 spontaneous preterm births and 21 indicated preterm births were analyzed separately. The odds ratios for preterm birth in the highest TAT quartile relative to the lowest quartile was 4.98 (95% confidence interval, 1.17-22.01; P = .007). CONCLUSION: We found a difference in the pattern of intraamniotic thrombin generation between women destined to deliver at term and those who deliver preterm, regardless of the type of preterm birth.

Evidence based medicine - decades later.

After more than two decades of enthusiasm surrounding the concept of evidence based medicine, wide variation in its implementation is still present. Some have suggested that evidence based medicine may be a failed model. We propose that the highly formulaic approach of evidence based medicine has evolved toward a more personalized, integrated and contextualized method, consistent with the principle of shared decision making advanced by the Institute of Medicine. Evidence based medicine remains an essential prerequisite but ultimately, only the practitioner's clinical expertise, knowledge and practical wisdom will provide the ability to apply general rules of evidence to particular clinical situations.

Antenatal corticosteroids after preterm premature rupture of membranes.

Preterm premature rupture of membranes (PPROM) is an obstetrical complication associated with high neonatal morbidity and mortality. The current management of PPROM focuses on neonatal benefit and includes the ancillary use of corticosteroids for fetal maturation. The purpose of this work was to provide a comprehensive and unbiased review of the available literature on prenatal administration of corticosteroids in conditions of PPROM, and to address the rationale and the relevant supporting evidence for this practice. We conclude that the cumulative level I evidence indicates a definite beneficial effect of corticosteroids in conditions of PPROM.

Factors related to corticosteroid utilization in preterm birth.

We sought to determine the rate of corticosteroid administration in preterm births in our institution and to describe factors associated with lack of corticosteroid exposure. We performed a retrospective case-control analysis. Of the 312 eligible women who delivered between 24 and 34 weeks' gestation, maternal corticosteroid administration was documented in 262 (84%) and no exposure in 50 (16%). A shorter admission to delivery interval (< 48 hours) decreased the likelihood of corticosteroid administration (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.03 to 0.28, P < 0.001). Use of tocolytics was associated with a lower risk of corticosteroid nonexposure (OR 0.21, 95% CI 0.04 to 0.69, P = 0.006). Lack of prenatal care was associated with an increased risk of corticosteroid nonexposure (OR 3.18, 95% CI 1.01 to 9.15, P = 0.01). The likelihood of corticosteroid administration was also decreased by gestational ages at the upper limit of the spectrum (33 to 34 weeks; OR 0.22, 95% CI 0.09 to 0.53, P < 0.001). The latter effect persisted after exclusion of premature rupture of membranes cases. In our population, factors associated with no maternal corticosteroid administration were shorter interval between admission and delivery, gestational age at the upper limit of the currently recommended interval for corticosteroid administration, and lack of prenatal care.

Antenatal corticosteroids in COVID-19 perspective.

The aim of this manuscript is to discuss the practice of antenatal corticosteroids administration for fetal maturation in severe acute respiratory syndrome coronavirus 2 positive pregnant women. Recent high-quality evidence supports the use of dexamethasone in the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Randomized disease outcome data have identified an association between disease stage and treatment outcome. In contrast to patients with more severe forms who benefit from dexamethasone, patients with mild disease do not appear to improve and may even be harmed by this treatment. Therefore, indiscriminate usage of fluorinated corticosteroids for fetal maturation, regardless of disease trajectory, is unadvisable. Obstetrical care needs to be adjusted during the COVID-19 pandemic with careful attention paid to candidate selection and risk stratification.

Management strategies for the prevention of preterm birth. Part I: Update on progesterone supplementation.

PURPOSE OF REVIEW: Preterm birth (PTB) is the main cause of neonatal morbidity and mortality in the developed world, generating a significant public health burden. PTB is a complex disorder and it is unlikely that one generalized prevention strategy will be effective in all patients. In this review, we are concerned with the most recent status of two proposed modalities of PTB prevention: progesterone supplementation and cerclage placement. Our intention was to emphasize the differential applicability of these two interventions tailored to specific clinical presentations. RECENT FINDINGS: Progress has been made in developing reliable prognosticators for PTB. Ultrasound cervical length measurement has emerged as the single most powerful predictor. Recent randomized trials of progesterone supplementation have indicated the relevance of this objective method of screening in the selection of patients most likely to respond to progesterone. Similarly, in studies of cerclage, cervical length has been found to perform as a tool capable of reducing unnecessary intervention. SUMMARY: Predefined treatment strategies guiding the decision on when to proceed with medical or surgical PTB prophylaxis are still lacking. On the basis of the available evidence, we suggest a differential approach giving preferential consideration to either progesterone or cerclage based on obstetrical history, cervical surveillance, and biochemical markers of inflammation.

Management strategies for the prevention of preterm birth: Part II - Update on cervical cerclage.

PURPOSE OF REVIEW: Cerclage was devised more than 50 years ago based on the hypothesis that for some women, weakness or malfunction of the cervix has a causative role in the pathway to preterm birth (PTB). There have been many theories around the concept of cervical insufficiency but not much in the way of convincing evidence. The purpose of this review was to follow the recent developments in risk identification and prognostication of PTB in connection with appropriately targeted prophylactic interventions. RECENT FINDINGS: Sonographic cervical length measurement has emerged as an effective prognosticator for PTB in all populations studied so far, independently of obstetric history, consequently deriving a wider applicability than other predictors of PTB. However, the mechanisms leading to cervical shortening are poorly understood, and it cannot be assumed that all cases with a short cervix would benefit from cerclage. Specific conditions may actually reduce the efficacy and advisability of cerclage. For this reason, attempts have been made recently to further characterize the short cervix, leading to the conclusion that only women with a short cervix in the absence of infection/inflammation may be candidates for cerclage. Furthermore, two recent randomized trials of cerclage in women with short cervix on a second trimester ultrasound suggested a benefit with cerclage in PTB rate reduction only in those cases with a cervical length of less than 15 mm. SUMMARY: The existent literature has treated PTB prevention focusing exclusively on either progesterone use or cerclage, leaving the practitioners without any guidance on when to proceed with medical or surgical prophylaxis. Understanding that high-risk populations are not homogeneous and no single-approach modality is likely to be generally applicable, we have combined the available evidence on both progesterone and cerclage to provide guidance on how to identify subgroups of women at significantly increased risk for PTB and how to preferentially consider progesterone versus cerclage.

Bone metabolism in pregnant women exposed to single compared with multiple courses of corticosteroids.

OBJECTIVE: To compare markers of maternal bone metabolism between women who received a single compared with multiple courses of antenatal corticosteroids. METHODS: This is an analysis of serum samples from a previously reported randomized, placebo-controlled, multicenter trial. Women at risk for preterm delivery after an initial course of corticosteroids were randomly assigned to weekly courses of betamethasone (active) or placebo. Serum levels of carboxy terminal propeptide of type I procollagen (PICP) and cross-linked carboxy terminal telopeptide of type I collagen (ICTP) were measured to assess the rate of bone formation and resorption, respectively, at three time points. The placebo group (n=93) was compared with the active group, receiving four or more courses of betamethasone (n=112). RESULTS: There were significant (P<.001) increases in PICP and ICTP between baseline and delivery in both groups. Cross-linked carboxy terminal telopeptide of type I collagen, but not PICP, was lower with corticosteroid exposure immediately before administration of the fourth study course (P<.001). No significant differences in PICP and ICTP were seen between groups at delivery. CONCLUSION: Increasing levels of PICP and ICTP with advancing gestation are consistent with physiologic changes in maternal bone metabolism. Multiple courses of corticosteroids for fetal maturation are not associated with persistent or cumulative effects on maternal bone metabolism as measured by PICP and ICTP. LEVEL OF EVIDENCE: II.

Pregnancy in women with renal disease. Part I: general principles.

The purpose of this review is to improve the basis upon which advice on pregnancy is given to women with renal disease and to address issues of obstetric management by drawing upon the accumulated world experience. To ensure the proper rapport between the respect for patient's autonomy and the ethical principle of beneficence, the review attempts to impart up-to-date, evidence-based information on the predictable outcomes and hazards of pregnancy in women with chronic renal disease. The physiology of pregnancy from the perspective of the affected kidney will be discussed as well as the principal predictors of maternal and fetal outcomes and general recommendations of management. The available evidence supports the implication that the degree of renal function impairment is the major determinant for pregnancy outcome. In addition, the presence of hypertension further compounds the risks. On the contrary, the degree of proteinuria does not demonstrate a linear correlation with obstetric outcomes. Management and outcome of pregnancies occurring in women on dialysis and after renal transplant are also discussed. Although the outcome of pregnancies under chronic dialysis has markedly improved in the past decade, the chances of achieving a viable pregnancy are much higher after transplantation. But even in renal transplant recipients, the rate of maternal and fetal complications remains high, in addition to concerns regarding possible adverse effects of immunosuppressive drugs on the developing embryo and fetus.