Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) through non-specialist providers and telemedicine: a study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven. METHODS: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms. DISCUSSION: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.

Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype.

This investigation is concerned with the kinetics of the reciprocal relationship between sheep hemoglobin (Hb) A and Hb C formation in response to anemia. The relative synthesis of the hemoglobin types was assessed at various times in bone marrow erythroid cells incubated in vitro with (59)Fe. The changeover from Hb A to Hb C formation lagged by about 3 days behind the development of anemia and was complete within about 11 days. After recovery from anemia the reciprocal change back to preanemic conditions proceeded at a much slower rate, Hb C formation gradually declining to unmeasurable levels over about 25 days. Infusions of plasma with high erythropoietin titre induced the formation of relatively large quantities of Hb C in erythroid cells of nonanemic sheep, demonstrating the central importance of a humoral mechanism in the change of expression of the hemoglobin genes. THE FOLLOWING CONCLUSIONS WERE DRAWN: hemoglobin phenotype is determined at a stem cell level. Erythroid stem cells appear to undergo gradual renewal. The identity of the plasma factor which induces Hb C formation is not yet known; it is not present in plasma from nonanemic sheep, and its production is not dependent upon hemoglobin genotype. If the plasma factor turns out to be erythropoietin, then this hormone must have an important influence on the pool of erythroid stem cells.

Effect of amniotic fluid bacteria on the course of labor in nulliparous women at term.

Patients with intraamniotic infection have an increased rate of cesarean delivery. To determine whether bacterial colonization of amniotic fluid affects uterine activity or delivery outcome, serial amniotic fluid samples were collected from 41 nulliparous patients in active labor with ruptured membranes for longer than 12 hours. To define positive changes, these samples were divided arbitrarily by colony count change using an increase of less than 10(2) colony-forming units per milliliter; greater than or equal to 10(2) but less than 10(4) colony forming units per milliliter; or greater than or equal to 10(4) colony forming units per milliliter. Nineteen, seven, and 15 sample sets fulfilled these criteria, respectively. Comparing serial samples with these changes in colony count revealed no significant difference in ten labor and delivery variables. Based on virulence of the isolates identified, samples were then divided into high (N = 19) or low (N = 16) virulence in both samples. Compared with sample sets with persistently low-virulence organisms, sample sets with persistently high-virulence isolates had a lower cervical dilatation rate (0.49 +/- 0.39 versus 0.98 +/- 0.58 cm/hour, P = .04), despite an increased maximum oxytocin dose (10.0 +/- 8.0 versus 5.4 +/- 5.2 mU/minute, P = .03). Controlling for birth weight, labor length, and epidural, magnesium sulfate, and oxytocin use, it was found that patients with high-virulence bacteria also had a higher cesarean section rate (57.9 versus 25.0%, P = .05). These results support a causal relationship between high-virulence bacteria in the amniotic fluid and poor cervical dilatation response to oxytocin in patients at risk for the development of intrapartum infection.

Percutaneous transvesical chorionic villus sampling: an alternative approach to the retroverted uterus.

In 458 consecutive chorionic villus sampling (CVS) procedures, we observed a significant influence of uterine position upon sampling efficacy. Compared with anteverted (N = 243) or axial (N = 149) locations, the retroverted uterus (N = 66) was associated with a lower mean sample weight per aspiration (22, 18, and 15 mg, respectively; P less than .01) and a greater frequency of multiple-pass procedures (23, 31, and 52%, respectively; P less than .0001). To improve sampling efficiency in selected cases of uterine retroversion, we adopted a transvesical approach. When compared with transabdominal or transcervical techniques, transvesical CVS had the highest single-pass success rate (33, 33, and 60%, respectively). Only one in 30 transvesical cases required three placental passes, compared with nine of 36 retroverted uteri sampled by either transabdominal or transcervical techniques (P less than .05). The mean transvesical sample weight was 18.7 mg; at least 10 mg was retrieved in all cases. Post-procedure bleeding occurred in four instances and an additional patient suffered a spontaneous loss at 16 weeks' gestation. Aneuploidy was found in four of 30 biopsy specimens, and the remaining pregnancies either have delivered at term (N = 18) or are continuing (N = 7). Our preliminary experience suggests that selected use of this CVS method may improve sampling efficiency without increasing the incidence of complications.

Fetal posterior urethral valve syndrome: a prospective application of antenatal prognostic criteria.

A case of posterior urethral valve syndrome is presented. Four weeks after a normal 24-week ultrasound examination, diminished amniotic fluid, megacystis, and renal hyperechogenicity were observed. A repeat ultrasound examination at 30 weeks' gestation identified oligohydramnios and increased renal echogenicity. These findings prompted the performance of a percutaneous cystocentesis to assess fetal renal function indirectly. The specimen was evaluated for osmolality and sodium and chloride concentrations. The urine electrolyte concentrations (sodium 115 mEq/L; chloride 93 mEq/L) and the osmolality (230 mOsm/L) were elevated, suggesting impaired renal function and a poor prognosis. Despite these findings, aggressive management was used, including administration of antenatal corticosteroids and elective preterm delivery. A percutaneous cystocentesis was required during the infant's initial resuscitation, followed by a difficult urethral catheterization. Ultimately, a vesicostomy performed on day 4 of life was associated with prompt return of renal function (serum creatinine 0.7 mg/dL at the time of discharge). At 6 months of age, normal renal function has been documented and the vesicostomy has been closed. This case demonstrates the potential limitations of available prognostic criteria in evaluating fetal urinary obstruction and residual renal function. In selected cases (when the onset of obstruction is documented in the third trimester), refinement of these prognostic criteria may be indicated. Similar cases may be best managed by preterm delivery and prompt postnatal decompression.

Fetal stroke associated with elevated maternal anticardiolipin antibodies.

Middle cerebral artery infarction explains some cases of congenital hemiparesis with or without neonatal stroke. The etiology of the stroke is often obscure. We describe two infants with imaging evidence of middle cerebral artery infarction whose mothers had elevated anticardiolipin antibody levels after delivery. We speculate that these antibodies may have been responsible for intrauterine thromboembolic stroke.

Randomized trial of antenatal dexamethasone in surfactant-treated infants delivered before 30 weeks' gestation.

OBJECTIVE: To determine if an additive effect exists between antenatal corticosteroid administration and postnatal surfactant therapy in the prevention of respiratory distress syndrome (RDS) in preterm infants. METHODS: A randomized, double-blind trial was conducted from April 1990 to June 1994, in which dexamethasone (5 mg every 12 hours for a total of four doses) or saline was given to women at risk for delivery at 24-29 weeks' gestation. At birth, prophylactic surfactant was administered to all study infants. Main outcome measures were RDS occurrence and severity. Secondary clinical end points included bronchopulmonary dysplasia, pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, retinopathy, intraventricular hemorrhage, and death. RESULTS: Seventy-five of the 124 randomized subjects delivered 96 infants within the studied gestational age range (dexamethasone, n = 54; placebo, n = 42). Similar maternal demographics and obstetric complications were noted between study groups. A greater population of infants were delivered from multi-fetal gestations in the dexamethasone cohort (26 of 54 versus 12 of 42 newborns; P = .05). There were no significant differences in the occurrence or severity of RDS between the dexamethasone and placebo infants (none or mild, 67 versus 67%; moderate, 24 versus 26%; severe, 9 versus 7%, respectively), or differences in any of the secondary clinical outcomes. The study size was sufficient to exclude a 50% reduction in RDS incidence as a consequence of dexamethasone exposure. An analysis restricted to singletons (dexamethasone, n = 28; placebo, n = 30) revealed similar overall occurrence of intraventricular hemorrhage (12 of 28 versus ten of 30; P = .63), but significantly fewer grade 3 and 4 intraventricular hemorrhages in dexamethasone-exposed neonates (two of 12 versus six of ten; P = .048). CONCLUSION: Antenatal dexamethasone does not appear to decrease the incidence or severity of RDS in surfactant-treated infants delivered at 24-29 weeks' gestation, but may be associated with reduced severity of intraventricular hemorrhages in surfactant-treated singletons in this gestational age range.

A comparison of pregnancy loss between transcervical and transabdominal chorionic villus sampling.

OBJECTIVE: To evaluate the comparative safety of transcervical and transabdominal chorionic villus sampling (CVS). METHODS: From May 1988 to January 1992, CVS was performed by two operators at 9-12 weeks' gestation in 1048 singleton pregnancies. The sampling method for each patient, transabdominal or transcervical, was chosen primarily based upon placental location; the transabdominal route was used for anterior or fundal location and the transcervical route for posterior placentation. Perinatal outcome was assessed by post-procedure patient telephone contact, mid-gestation ultrasound evaluation, postpartum questionnaire completed by the referring obstetrician, and telephone interview with each patient after delivery. RESULTS: Complete follow-up was available in 1012 cases (97%). Excluding 39 elective abortions, 35 of 973 euploid pregnancies aborted spontaneously. The difference in fetal loss rate between transcervical and transabdominal CVS approached statistical significance (5.2 versus 2.9%; P = .058). Bleeding before CVS (P = .006) and multiple placental aspirations (P = .022) were associated with fetal loss for the entire study group. An interaction between uterine position and sampling method was also indicated; an increased loss rate was associated with transcervical CVS in the presence of uterine retroversion (P = .0017). CONCLUSION: Despite choosing the preferred CVS method for each patient, an increased loss rate may be associated with transcervical sampling in the presence of uterine retroversion.

Immunologic studies in presumed amniotic fluid embolism.

OBJECTIVE: To evaluate the potential role of immunologic mechanisms that involve mast cell degranulation (anaphylaxis) or complement activation in the mechanism of amniotic fluid embolism. METHODS: This study was a case series of nine women with presumed amniotic fluid embolism and a control group of 22 women who had normal labor. Women were from community and tertiary referral hospitals in Japan and the United States. Main outcome measures were maternal peripartum complement levels (C3 and C4), serum levels of tryptase, urinary histamine concentrations, and serum levels of a fetal antigen (sialyl Tn). RESULTS: Serum tryptase and urinary histamine measurements were negative in women with amniotic fluid embolism; seven of nine had elevated levels of fetal antigen. All eight who had serum available for testing had abnormally low levels of complement. Mean C3 level of 44.0 mg/dL and C4 level of 10.7 mg/dL were significantly lower than corresponding postpartum control values of 117.3 mg/dL and 29.4 mg/dL (P =.018 for C3, P =.012 for C4). Postpartum C3 and C4 levels decreased by 8% and 5%, respectively, compared with intrapartum values (P =.003 for C3, P =.021 for C4) but were still within normal range. CONCLUSION: Serologic findings suggest a role for complement activation in the mechanism of amniotic fluid embolism. Laboratory data from this series did not implicate mast cell degranulation (anaphylaxis) in the pathophysiology of the disease.

Clinical implications of atypical chromosome abnormalities diagnosed prenatally.

OBJECTIVE: To determine the frequency of atypical aneuploidy resulting from prenatal testing and assess the implications of these diagnoses on prenatal decision making. METHODS: We reviewed all amniotic fluid and chorionic villus samples obtained between January 1994 and September 1997 and grouped the abnormal cases into typical or atypical subcategories. This distinction was based upon whether the diagnosis provided a straightforward range of prognoses or an ambiguous clinical implication. Results were stratified by sample source to determine whether atypical aneuploidy was more commonly seen in cultures of chorionic villi or amniocytes. We also evaluated the influence of ultrasound findings on prenatal decision making in atypical aneuploid cases. RESULTS: Of 2960 samples, 134 were abnormal (4.4%), with 27 of 134 abnormalities (20%) representing atypical aneuploidies. The percentages of chorionic villus and amniocentesis cases complicated by atypical aneuploidy (22% and 78%, respectively) were consistent with the distribution of procedures in the entire study. Ultrasound abnormalities did not invariably prompt a decision to terminate pregnancy (only two terminations of six fetuses with congenital malformation), whereas atypical karyotypes led to termination even in the presence of normal-appearing fetal anatomy (five terminations of 21 without malformations; P = .63). CONCLUSION: The frequency of atypical aneuploidy resulting from prenatal diagnosis was approximately 1.0%, and these cases represented 20% of all abnormal karyotypes observed. The ambiguity conferred by atypical aneuploidy can influence a family's decision making, even in the presence of normal ultrasound findings.

Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity.

OBJECTIVE: To compare lamellar body counts with the lecithin/sphingomyelin ratio and phosphatidylglycerol analysis in terms of assessment of risk of respiratory distress syndrome (RDS). METHODS: Lamellar body counts, lecithin-sphingomyelin ratios (L/Ss), and phosphatidylglycerol levels were assessed in 1611 amniotic fluid samples obtained at four clinical sites from pregnant women whose fetuses were at risk for RDS. Cases in which delivery occurred within 72 hours of sample collection (n = 833) were analyzed. Specific cutoffs for predicting the likelihood of RDS for both the lamellar body count and the L/S had been derived previously at each of the clinical sites based on receiver operating characteristic curves using unrelated samples, whereas phosphatidylglycerol was reported as either mature (present) or immature (absent). Standard clinical and radiographic criteria were used to diagnose RDS, and the diagnosis was confirmed by review of newborn records. RESULTS: One hundred (12.0%) of the 833 infants delivered within 72 hours of sample collection developed RDS. The negative predictive value of the lamellar body count (97.7%) was similar to that of the L/S (96.8%) and slightly better than that of phosphatidylglycerol analysis (94.7%) (P =.048). The lamellar body count performed as well as phospholipid analysis irrespective of gestational age or patient population. CONCLUSION: The lamellar body count compares favorably with traditional phospholipid analysis as an assay for assessment of fetal lung maturity. Lamellar body counts are preferable because they are faster, more objective, less labor intensive, less technique dependent, and less expensive and because they can be performed with equipment available in every hospital laboratory.

Late first-trimester invasive prenatal diagnosis: results of an international randomized trial.

OBJECTIVE: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. METHODS: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. RESULTS: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. CONCLUSION: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. LEVEL OF EVIDENCE: I

Multifetal reduction increases the risk of preterm delivery and fetal growth restriction in twins: a case-control study.

OBJECTIVE: To compare pregnancy outcome in twin gestations resulting from multifetal reduction to "primary" twin pregnancies derived from either spontaneous conception or infertility therapy. DESIGN: Case-control study. SETTING: University-affiliated tertiary center. PATIENT(S): Multifetal pregnancies (quadruplets or more) reduced to twins (group A) compared with twin gestations conceived either spontaneously (group B) or through infertility therapy (group C). INTERVENTION(S): Multifetal reduction for group A; perinatal care for groups A, B, and C. MAIN OUTCOME MEASURE(S): Comparison of perinatal complications between groups including antepartum bleeding, premature membrane rupture, and preterm labor. Neonatal outcomes compared including gestational age at delivery, birth weight, incidence of fetal growth restriction, and twin discordancy. RESULT(S): A higher incidence of idiopathic preterm labor was noted in group A cases (14/18) compared with either of the control groups (B: 26/54, or C: 24/54). As a consequence, group A had the lowest gestational age at delivery (32.6 +/- 3.9 weeks) compared with groups B (33.6 +/- 4.4 weeks) and C (36.0 +/- 3.4 weeks). Corresponding birth weights of both first- and second-born twins were significantly lower in group A compared with group C, whereas the birth weight comparison between groups A and B showed a nonsignificant difference. The proportion of pregnancies in which one or both twins weighted less than the 10th percentile was greatest in group A pregnancies (A: 5/18 versus C: 5/54). Discordant birth weight among twin pairs was proportionately greater for group A cases at both the 20% and 30% discordance levels. CONCLUSION(S): Twin gestations resulting from multifetal reduction are at increased risk for preterm birth, fetal growth restriction, and discordancy when compared with fertility therapy-derived, nonreduced twins.

Differential effects of endothelin A and B receptor antagonism on fetal growth in normal and nitric oxide-deficient rats.

OBJECTIVE: To determine the role of endothelin (ET) in fetal and placental growth in rats with and without long-term nitric oxide synthase (NOS) inhibition. METHODS: Pregnant rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline and with one of three ET receptor antagonists or vehicle. The antagonists included A-182086 (nonselective) as well as A-127722 and FR-139317 (both ET(A) selective). Treatment was begun on day 14 of gestation. On gestational day 21, a hysterotomy was done. Litter size was recorded, and viability and fetal and placental weights were determined. Results were analyzed by analysis of variance or by a Kruskal-Wallis nonparametric analysis. RESULTS: In the absence of L-NAME, fetal and placental weights were not affected by ET(A)-selective antagonism but were significantly decreased by nonselective receptor antagonism (P <.001 and P <.05 for fetal and placental weights, respectively). Infusion of L-NAME resulted in fetal and placental growth restriction (P <.001). In the setting of L-NAME infusion, fetal and placental weights were increased by the ET(A)-selective antagonists (P <.01) but not by the nonselective antagonist, compared with weights from animals treated with L-NAME alone. There were more fetal deaths with L-NAME treatment (P <.05), but their occurrence was not significantly affected by any of the ET receptor antagonists. CONCLUSIONS: Endothelin-A antagonism alone did not affect fetal or placental growth, whereas combined ET(A) plus ET(B) antagonism produced fetal and placental growth restriction. In the setting of long-term NOS inhibition, ET(A)-selective antagonism improved fetal and placental growth, whereas antagonism of both ET(A) and ET(B) receptors did not. Endothelin contributes to NOS inhibition-induced growth restriction acting through the ET(A) receptor.

Serum from patients with severe preeclampsia is not cytotoxic to endothelial cells.

OBJECTIVE: We evaluated the hypothesis that circulating factors in preeclampsia promote direct endothelial cell injury using an in vitro index of cytotoxicity. METHODS: Subconfluent umbilical vein endothelial cell monolayers were established and radiolabeled with chromium (51Cr), then randomly exposed for 24 hours in triplicate to 20% sera from nonlaboring patients with severe preeclampsia (n = 5) or mild preeclampsia and normotensive controls (n = 5). Additional experiments were performed by exposing endothelial monolayers to sera for 3 and 48 hours, and under hypoxic conditions (1% oxygen). Cytotoxicity was defined by the percentage of 51Cr release, expressed as the ratio of radioactivity in the supernatant to the maximum cell-associated radioactivity. RESULTS: Mean 51Cr release was similar in all experiments comparing preeclamptic and normal sera. Although consistently greater 51Cr release was noted in hypoxic as compared with normoxic incubations, no differences in cytotoxicity were identified among severe preeclampsia, mild preeclampsia, and normal sera in hypoxia. CONCLUSION: Sera from patients with preeclampsia do not appear to be cytotoxic to vascular endothelium in this in vitro model.

Comparison of active phase labor between triplet, twin, and singleton gestations.

OBJECTIVE: To characterize the active phase of labor in triplet pregnancies and compare it with gestational age-matched twins and singletons. METHODS: Active phase rates were calculated beginning at 5 cm of dilation for women with triplet gestations longer than 24 weeks who labored and reached the second stage. Twin and singleton cohorts that also completed the first stage of labor were matched for gestational age at delivery (+/-1 week), parity, and epidural use. Intrapartum variables included oxytocin use (induction or augmentation, duration of infusion, and maximum dosage), cervical dilation at membrane rupture, and active phase dilation rate. RESULTS: Thirty-two triplet pregnancies met inclusion criteria between January 1994 and September 1998 and were each compared with twin and singleton cases in a 1:2 ratio. Triplet and twin active phase rates, while similar (1.8 versus 1.7 cm/hour, respectively), were significantly lower than the mean singleton dilation rate (2.3 cm/hour, P =.02). No other intrapartum variables differed between the three groups. Despite controlling for gestational age at delivery, mean birth weights were significantly higher in singletons and correspondingly lower in twins and triplets (2,493 versus 2,112 and 1,968 g, respectively; P =.001). An analysis of active phase dilation rates as a function of the cumulative birth weight per pregnancy demonstrated an inverse correlation, with slower progress in active labor associated with increasing total fetal weight (R = -.24; P =.002). CONCLUSIONS: Triplet and twin active phase dilation proceeds at a slower rate than that observed in singleton pregnancies. The rate of active phase dilation is inversely correlated to total fetal weight.

The perinatal management of central nervous system anomalies.

The diagnosis, proper evaluation, and treatment of a CNS anomaly requires the participation of many subspecialists and support personnel. The outcome can be favorably modified through the choice of elective termination, aggressive or passive perinatal intervention, and the 24-hour availability of neurosurgical expertise. At the conclusion of the pregnancy, accurate and informative counseling also should be provided. Although these discussions need not take place immediately, review of the final diagnosis, its risk of recurrence, and the appropriate screening for subsequent pregnancy should be included.

Understanding prostaglandin metabolites and platelet-activating factor in the pathophysiology and treatment of the antiphospholipid syndrome.

As clinicians include an immunologic evaluation in their assessment of recurrent fetal loss among otherwise asymptomatic women, the diagnosis of PAPS will be uncovered with greater frequency. Our understanding of the underlying pathophysiology of PAPS is critical if we are to propose safe and rational therapies for these patients. It appears as though prostaglandin metabolites are implicated directly in the processes that culminate in this unique, localized vasculopathy; and research is actively progressing with this focus in mind. For the present, we should look critically at the available treatments to be sure that the rationale for use is consistent with current evidence and that the margin of fetal and maternal safety justifies their use. To date, only low-dose aspirin appears to alter prostaglandin metabolites favorably and is thus, emerging as our safest and most efficacious treatment.

Perinatal management of meconium staining of the amniotic fluid.

The pathogenesis of meconium passage and the pathophysiology of meconium aspiration are reviewed. Intrapartum and neonatal strategies for the prevention of meconium aspiration syndrome are presented in historical perspective, and newer interventions are appraised.

Antenatal steroid therapy before 33 weeks' gestation.

OBJECTIVE: The purpose of this study was to determine those factors influencing contemporary antenatal steroid use in pregnancies delivered prior to 33 weeks of gestation. METHOD: We analyzed the clinical circumstances of 86 consecutive patients who delivered prior to 33 weeks of gestation and compared to 20 women who received dexamethasone prior to delivery with the remaining 66 untreated cases. RESULT: Known risk factors for preterm delivery (e.g. prior preterm birth, n = 17; prior admission and tocolysis during the index pregnancy, n = 15) did not discriminate between treated and untreated subsets. Premature membrane rupture (3/20 vs. 34/66; P < 0.01) and documented preterm labor (1/20 vs. 23/66 P < 0.01) were more common in the untreated cohort and a shorter mean interval from admission to delivery was also observed (2.8 vs 11.2 days). However, a full course of steroids would have been possible in 22/66 untreated women, since delivery was delayed for at least 36 h in these patients. CONCLUSION: These observations reflect the fact that many preterm births cannot be anticipated, even among hospitalized patients. We would therefore suggest that universal steroid treatment be considered for all women with documented preterm labor prior to 33 weeks of gestation. Initiation of steroid therapy at the referral center, (prior to maternal transport) should also be considered. Since both premature membrane rupture and early gestational age (24-28 weeks') confounded many of these cases, steroid use in patients with these circumstances should be reevaluated.