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.

Severe perineal laceration during operative vaginal delivery: the impact of occiput posterior position.

OBJECTIVE: To identify risk factors for severe (third/fourth degree) perineal laceration with operative vaginal delivery (OVD, forceps or vacuum). STUDY DESIGN: Case-control study comparing singleton OVDs with or without severe laceration (n=138). RESULT: In multivariable analyses, severe perineal laceration was associated with occiput posterior (OP) position at delivery, vaginal nulliparity, use of forceps, longer period pushing in the second stage and lower gestational age, but not birth weight, labor induction or episiotomy. Among 29 OP patients at full dilation, 9/13 (69%) attempted rotations to occiput anterior (OA) were successful, and 14/16 (88%) patients in whom rotation was not attempted remained OP at delivery. Successful rotation from OP to OA was associated with fewer severe lacerations than no attempt or unsuccessful rotation (22 vs 75%, P=0.01). CONCLUSION: Severe perineal laceration during OVD is associated with OP position at delivery and is reduced threefold in patients successfully rotated from OP to OA.

Psychosocial assessment by phone for high-scoring patients taking the Edinburgh Postnatal Depression Scale: communication pathways and strategies.

The well-documented risks associated with perinatal depression provide a strong argument for universal screening. However, uncertainty about what to do with findings is a significant barrier to implementing screenings where obstetric care is provided. Based on experience with a comprehensive screening program, we describe a protocol for those critical communication pathways that encourage a dynamic phone exchange between a mental health caller and the patient who has scored in the high range on the Edinburgh Postnatal Depression Scale. In addition, we present guidelines for developing an action plan for addressing intervention needs and closing the feedback loop to the original administrators of the scale.

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

First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique.

OBJECTIVE: To describe the process of training for measuring nuchal translucency at five clinical centers in North America and to evaluate methods of quality assurance and feedback. DESIGN: Throughout a period of 18 months, the performance of sonographers in measuring fetal nuchal translucency was monitored using qualitative and quantitative methods of review. After 12 months, different approaches (written and personal feedback) were used to inform sonographers of technical aspects that needed to or could be improved. RESULTS: On initial qualitative review, discrepancies in judgment from different reviewers coincided with suboptimal magnification, failure to visualize the amniotic membrane and/or use of cross-shaped calipers. At subsequent global review, 13 (29%) images of nuchal translucency measurements were considered unacceptable. Quantitative assessment revealed that, during the first part of the study, the means from four sonographers were significantly smaller and the mean from the fifth sonographer was significantly larger than expected on the basis of findings from The Fetal Medicine Foundation (P < 0.0001). Following feedback, sonographers who underestimated nuchal translucency and who received a written report only did not change measurements overall (P = 0.9759). In contrast, those who received additional intervention showed a marked difference (P < 0.0001). CONCLUSIONS: Global qualitative review of images from one sonographer may be preferable to assessment of individual aspects of images. Results from global qualitative review correspond well with findings from quantitative analysis, indicating that the latter can be applied for ongoing audit. Observation of divergent results should prompt extensive personal feedback, rather than a written report, to prevent sonographers from settling in their own, inappropriate technique.

A reappraisal of amniotic fluid alpha-fetoprotein measurement at the time of genetic amniocentesis and midtrimester ultrasonography.

OBJECTIVE: To evaluate the contemporary utility of amniotic fluid alpha-fetoprotein measurement as a complementary test for fetal abnormalities at the time of invasive genetic testing. METHODS: A review of amniotic fluid alpha-fetoprotein test results was conducted to determine the frequency with which elevated alpha-fetoprotein values added independent diagnostic information and altered clinical management. Amniotic fluid specimens processed for alpha-fetoprotein between 1995 and 1998 were included. Elevated alpha-fetoprotein cases were classified as either incidental to the fetal abnormality diagnosed or central to the identification of a fetal anomaly on the basis of whether an ultrasonographic examination had already identified the anomaly before amniocentesis. The costs associated with alpha-fetoprotein testing were used to estimate the expenditure per pregnancy in which elevated alpha-fetoprotein values would add discriminatory diagnostic value. A hypothetical national cost model was constructed to explore the utility of selective rather than routine amniotic fluid alpha-fetoprotein measurement. RESULTS: Eighty-two (3%) of 2769 amniotic fluid alpha-fetoprotein values were elevated. In only 1 instance was the elevated result found to be partially discriminatory (e.g., an established diagnosis of microcephaly with an associated small encephalocele identified after the elevated amniotic fluid alpha-fetoprotein value prompted repeated ultrasonographic assessment). Sixty-one other neural tube defects were detected by ultrasonography alone (myelomeningocele, n = 28; anencephaly, n = 24; and encephalocele, n = 9). Thus, an elevated alpha-fetoprotein result added diagnostic precision in only 1 (0.036%) of 2769 cases. Cost estimates suggested that routine amniotic fluid alpha-fetoprotein assessment resulted in a $219,000 expenditure per informative case. CONCLUSIONS: Routine measurement of amniotic fluid alpha-fetoprotein during amniocentesis may not be warranted in centers with expertise in targeted ultrasonographic imaging.

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.

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.

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.

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.

A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group.

OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen. STUDY DESIGN: This multicenter, randomized, double-blind pilot study compared treatment with heparin and low-dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at

Optional vaginal delivery rate. An informative indicator of intrapartum care.

OBJECTIVE: To determine whether an "optional" vaginal delivery rate and novel delivery score would provide informative profiles of intrapartum care. STUDY DESIGN: Prospective survey of all parturients delivering between January and December 1996. Deliveries were categorized as standard-vaginal (V-S), optional-vaginal (V-O), standard-cesarean (C-S) or potentially avoidable-cesarean (C-PA) using specific perinatal criteria derived from the literature. A weighted equation was developed and applied, generating physician delivery scores, giving "extra credit" for V-O and a "debit" for C-PA: delivery score = [(% V-O x 2) + (% V-S) - (% C-PA] x 100. RESULTS: V-O rates and delivery scores ranged from 0% to 25% and from 52 to 113, respectively (medians of 9.8% and 92.9). Among the obstetricians (n = 38), a significant inverse correlation was noted between the total C-S rates and V-O rates (r = -.54, P < .005). The maternal-fetal medicine physicians (n = 6) had high total C-S rates (22-36%) but also had high V-O rates (17.1-23.5%) and high delivery scores (82.1-101.5). CONCLUSION: The optional vaginal delivery rate and delivery score are more-informative indicators of intrapartum management acumen than is cesarean section rate alone. We suggest incorporating these descriptors into departmental quality assurance programs.

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.

Timing of labor induction after premature rupture of membranes between 32 and 36 weeks' gestation.

OBJECTIVE: The objective was to determine a consensus gestational age for labor induction after premature rupture of membranes between 32 and 36 weeks' gestation on the basis of the relative frequencies of adverse neonatal outcomes. STUDY DESIGN: A retrospective review was undertaken of all patients with premature rupture of membranes between 32 and 36 weeks' gestation. These patients were managed expectantly whenever possible. Neonatal outcomes were stratified by gestational age at rupture of membranes. RESULTS: Two hundred thirty-six patients with rupture of membranes between 32 and 36 weeks' gestation were managed expectantly. Prolongation of pregnancy by >/=1 week was infrequent in all cases, particularly if membrane rupture occurred after 34 weeks' gestation. Reductions in the neonatal length of stay and the incidence of hyperbilirubinemia were observed at 34 weeks' gestation with respect to younger gestational ages. No perinatal deaths occurred among the study cases. CONCLUSIONS: A "break point" in neonatal morbidity was observed at 34 weeks' gestation, which supports induction of labor at this gestational age. The short latencies observed limit the potential benefits of expectant management.

Neonatal outcomes in triplet gestations after a trial of labor.

OBJECTIVE: This study aimed to compare neonatal outcomes in a cohort of triplet gestations undergoing a trial of labor with those of a similar cohort delivered by elective cesarean delivery. STUDY DESIGN: Thirty-three women with triplet gestations who underwent a trial of labor were compared with a matched cohort of 33 women with triplet gestations who were delivered of their infants by elective cesarean delivery. Neonatal outcomes assessed included respiratory distress syndrome, retinopathy of prematurity, necrotizing enterocolitis, intraventricular hemorrhage, Apgar scores, and birth trauma. RESULTS: Twenty-nine of 33 women (87.9%) who underwent a trial of labor had a successful vaginal delivery of all 3 neonates. One patient was delivered of her first triplet vaginally but then required a cesarean delivery for abruptio placentae; 3 other patients were delivered of their infants by cesarean section for active-phase arrest of labor. There were no differences in neonatal outcomes between the 2 groups, although triplet neonates delivered by elective cesarean section demonstrated a trend toward a greater incidence of respiratory distress syndrome (P = .09). CONCLUSION: Our experience suggests that offering vaginal delivery is an acceptable management plan for triplet gestations.

Midtrimester amniocentesis. Influence of operator caseload on sampling efficiency.

OBJECTIVE: To evaluate the impact of operator caseload on the sampling efficiency for early and standard, midtrimester amniocentesis. STUDY DESIGN: Prospective ascertainment of genetic amniocenteses performed during 36 months, grouped into early (13-14 weeks' gestation) and standard procedures (15-20 weeks' gestation). Details of each amniocentesis were recorded immediately after sampling, and pregnancy outcomes were retrieved via questionnaires completed by the delivering physician. Sampling efficiency was evaluated separately in the early and standard cohorts in relation to operator caseload. RESULTS: In total, 193 and 707 patients underwent early and standard amniocentesis, respectively. Forty of 46 physician-operators performed < 50 total procedures during the study interval (group A). When compared to operators performing > or = 50 cases (group B, n = 6), a higher rate of single-pass success was noted among group B physicians for both early and standard procedures (A vs. B, early: 40/45 vs. 145/148, P = .018; standard: 243/295 vs. 384/412, P < .0001). Logistic regression confirmed an independent effect of physician caseload on sampling efficiency and a significant interaction between physician caseload and simultaneous ultrasound guidance in predicting single-attempt success. CONCLUSION: Operator caseload directly influenced sampling efficiency for both early and standard, midtrimester amniocentesis.

Perinatal outcome associated with outpatient management of triplet pregnancy.

OBJECTIVE: Our goal was to compare the lengths of hospitalization and the perinatal outcomes of triplet pregnancies managed with either outpatient or inpatient third-trimester bed rest. STUDY DESIGN: Thirty-two triplet pregnancies in which outpatient bed rest was prescribed (April 1993 to April 1996) were compared with a historic cohort of 34 triplets (January 1985 to March 1993) in which routine hospitalization was undertaken in the third trimester. Length of hospitalization and maternal and neonatal outcome parameters were compared between groups. RESULTS: Maternal inpatient hospital days were significantly reduced for the group managed as outpatients, but combined maternal and neonatal hospitalization was similar between groups. The mean gestational age at delivery was 1 week greater in the hospitalized cohort (33.5+/-2.8 vs 32.5+/-2.8, respectively; p=0.16), and average birth weight was correspondingly greater in hospitalized cases (1942 gm vs 1718 gm, p < 0.005). Neonatal lengths of stay were similar between groups, reflecting earlier postnatal discharge in the outpatient era of this study. Preeclampsia occurred with greater frequency in the outpatient group (31.3% vs 8.8%, p=0.02), and the neonatal complication of intraventricular hemorrhage occurred more commonly in this cohort as well (10/96 vs 1/102, p=0.004). All other maternal and neonatal complications were similar between groups. CONCLUSION: Reduction in the length of hospitalization attributable to outpatient management was limited to the maternal length of stay. It is possible that the observed maternal and neonatal complications in the outpatient group may have been related to less rigorous bed rest. We would suggest that the differences noted in preeclampsia, birth weight, and intraventricular hemorrhage support prospective evaluation of bed rest in triplet pregnancy.

Endothelin-1-induced placental and fetal growth restriction in the rat.

The objective of this study was to evaluate the effect of increased circulating endothelin on fetal and placental growth in the rat. Indwelling arterial and venous catheters were placed on day 14 of a 22-day gestation in timed-pregnant Sprague-Dawley rats. Saline, 0.2 nmol/kg/h endothelin, or 0.5 nmol/kg/h endothelin was continuously infused from day 15 through 21 in randomly assigned animals (n = 12 in each group). Maternal arterial blood pressure and serum endothelin levels were evaluated on days 15, 18, and 21 of gestation. On day 21, pregnancy outcome data including fetal and placental weights, litter size, and the occurrence of stillbirths were ascertained, and fetal blood was obtained for serum endothelin levels. All data were compared among the three groups, and statistical significance was determined by analysis of variance. Endothelin infusion resulted in a dose-dependent decrease in fetal and placental weights when compared to saline-treated pregnancies. A significant increase in maternal arterial blood pressure was noted only in the 0.5 nmol/kg/h endothelin group. Fetal and placental growth restriction occurred in the absence of maternal hypertension in the 0.2 nmol/kg/h group. These results demonstrate that endothelin infusion causes restriction of fetal and placental growth, even in the absence of maternal hypertension.

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.