Buprenorphine Induction Using Microdosing for the Management of Opioid Use Disorder in Pregnancy.

Background Conventional buprenorphine inductions require patients to abstain from full agonist opioids until they experience mild-to-moderate opioid withdrawal. We described a successful buprenorphine induction case in a pregnant patient using microdosing, which avoided withdrawal symptoms. Case Presentation The patient is a 29-year-old G2P1001 at 18 2/7 weeks of gestation, who desired a switch from methadone to buprenorphine to minimize neonatal opioid withdrawal syndrome (NOWS), which complicated her last pregnancy. She was given increasing microdoses of buprenorphine over a 7-day period, while continuing her daily dose of methadone. She discontinued the methadone on day 8. She did well during the week of buprenorphine microdosing, with no complaints of withdrawal or cravings. She was engaged in her prenatal care. Her dose of buprenorphine was increased to 8 mg twice daily in the third trimester for some withdrawal symptoms in the evening consisting of new onset nausea and vomiting. The patient underwent an elective 39-week induction of labor and had a spontaneous vaginal delivery of an appropriately grown male fetus. Only nonpharmacologic interventions were used. Conclusion Buprenorphine microdosing was well tolerated in this patient and avoided withdrawal symptoms in the mothers, and NOWS. A microdosing study in pregnancy is indicated.

Randomized Trials of Retosiban Versus Placebo or Atosiban in Spontaneous Preterm Labor.

OBJECTIVE: The aim of this study is to assess the efficacy and safety of retosiban in spontaneous preterm labor (sPTL). STUDY DESIGN: Two multicenter, randomized, and double-blind trials compared retosiban with placebo and retosiban with atosiban in women with a singleton pregnancy and intact membranes in sPTL at 24 to 336/7 weeks' gestation. Coprimary endpoints in the placebo-controlled trial were time to delivery (TTD) or treatment failure (whichever occurred first) and neonatal composite morbidity and mortality. The primary endpoint of the atosiban comparator trial was TTD. RESULTS: The trials were terminated early because of slow recruitment. The placebo-controlled trial enrolled 23 participants (February 2016-July 2017; 2.6% of target);the atosiban-comparator trial enrolled 97 (March 2015-August 2017; 29% of target). Baseline participant characteristics were similar between treatments. In the placebo-controlled trial, mean gestational ages at randomization were 30.8 (retosiban, n = 10) and 30.5 weeks (placebo, n = 13), and mean times to delivery/treatment failure were 18.9 days (retosiban) and 11.1 days (placebo). Two and four neonates in the retosiban and placebo groups, respectively, had ≥1 component of the neonatal composite endpoint. In the atosiban-comparator trial, mean gestational age at randomization was 31.5 weeks (for both retosiban, n = 47, and atosiban, n = 50), and adjusted mean TTDs were 32.51 days (retosiban) and 33.71 days (atosiban; p > 0.05). Adverse events were no more common with retosiban than placebo or atosiban. CONCLUSION: Despite considerable efforts to conduct two adequate and well-controlled studies in patients with sPTL, both studies were unable to recruit effectively and consequently terminated prematurely. Key factors negatively affecting participation were patient and physician resistance to use of a placebo comparator, lack of investigator consensus on diagnostic criteria and acceptance of protocol procedures, and ethics committee decisions. Meaningful cooperation between pharmaceutical companies, regulatory authorities, and the obstetric community is essential for future development of drugs to treat sPTL.

Opioid Addiction in Pregnancy: Does Depression Negatively Impact Adherence With Prenatal Care?

OBJECTIVE: We aimed to evaluate whether depression in pregnancy in women with opioid dependency negatively impacts adherence with prenatal care. METHODS: This was a retrospective chart analysis of opioid-dependent pregnant women over a 6-year period at 2 large referral and tertiary care centers. The primary outcome was adherence with prenatal care based on the concurrent diagnosis of depression. Adherence was assessed by looking at the number of observed versus expected prenatal visits. Secondary outcomes included neonatal intensive care unit (NICU) stay, and incidence and severity of neonatal abstinence syndrome (NAS). RESULTS: A total of 74 patient charts were reviewed. 45/74 (60.8%) of the opioid-dependent pregnant patients were either diagnosed with depression (n = 41), anxiety (n = 2), or scored >10 on the Edinburgh Prenatal Depression Scale (n = 1). Patients with a diagnosis of depression were significantly less adherent with prenatal care; 80% adherent (73% vs 93%; P = 0.03), 90% adherent (62% vs 93%; P = 0.003). A higher number of patients in the depression group had an infant treated for withdrawal (62% vs 38%; P = 0.041), and had longer NICU stays (27% vs 21%; P = 0.018). Analysis of the whole cohort of opioid dependent gravidas revealed Buprenorphine maintenance therapy had the lowest mean NAS score 6.5 ±â€Š4.4, compared with methadone maintenance 10.6 ±â€Š3.6, and no maintenance therapy 9.4 ±â€Š4.0 (P = 0.008). CONCLUSION: Depression negatively impacts adherence with prenatal care and was significantly associated with a higher incidence of neonatal withdrawal and longer NICU stays. Buprenorphine therapy had the lowest incidence and severity of NAS when compared with methadone and no maintenance therapy.

Perinatal and Neonatal Outcomes of Triplet Gestations Based on Chorionicity.

Objective To compare perinatal and neonatal outcomes of dichorionic (DC) and monochorionic (MC) with trichorionic (TC) triplet gestations. Methods A retrospective cohort study of DC + MC versus TC triplet gestations delivered at a tertiary care hospital from 2009 to 2015. The results include 42 sets of triplets (TC, n = 26; DC + MC, n = 16). Maternal demographics and pregnancy data were compared. Neonatal outcomes were assessed using composite morbidity and mortality. Results Maternal baseline characteristics including age, mode of conception, race, parity, body mass index, and previous preterm delivery were statistically comparable. Comparison of prenatal management and complications yielded no significant differences in terms of presence of shortened cervix, cerclage placement, use of tocolytics, intrauterine growth restriction, premature rupture of membranes, pregnancy-induced hypertension, or gestational diabetes. However, evaluation of composite morbidity and mortality (RDS, IVH, NEC, IUGR, and death) illustrated that all infants born from DC + MC triplet gestations suffered some morbidity or mortality compared with TC pregnancies (p < 0.01). Conclusion DC + MC triplet gestations are at an increased risk of neonatal morbidity and mortality compared with TC triplet gestations.

Management of Breast Cancer during Pregnancy: Are We Compliant with Current Guidelines?

Introduction The purpose of this study was to evaluate the management of patients with breast cancer in pregnancy treated at the Advocate Health Care, to determine whether these patients were treated according to guidelines for pregnant patients, which aim to maximize both fetal and maternal outcomes. Methods A retrospective chart review was performed at the Advocate Lutheran General Hospital, Christ Medical Center, and Illinois Masonic Medical Center from 2002 to 2012 on patients diagnosed with breast cancer during pregnancy using ICD-9 (International Classification of Diseases - 9th version) codes. Results Eleven patients between 12 and 37 weeks' gestation matched the search criteria. One patient terminated the pregnancy. Patients in our study were treated appropriately according to guidelines with the following exceptions. Trastuzumab was used in one patient during pregnancy which likely caused the oligohydramnios resulting in an induction of labor at 33 weeks. Three patients were delivered preterm between 34 and 36 weeks without an obstetric indication. Two patients underwent sentinel node biopsy. Conclusion The diagnosis of breast cancer in pregnancy is an infrequent but devastating diagnosis that is likely to increase. Although sentinel lymph node biopsy is not generally recommended in pregnancy, this may be an outdated guideline as using a low-dose lymphoscintigraphic technique appears to be safe in pregnancy.

Diagnosing Pulmonary Embolism in Pregnancy: Are Biomarkers and Clinical Predictive Models Useful?

Objective The objective of this study was to evaluate whether trimester-specific D-dimer levels or the modified Wells score (MWS) is a useful risk stratification tool to exclude pregnant women at low risk of pulmonary embolism (PE) from diagnostic imaging. Study Design This is a prospective and retrospective cohort study. Pregnant women who underwent diagnostic imaging for suspected PE were prospectively enrolled. D-dimer serum levels were drawn, and a MWS was assigned. Pregnant women diagnosed with a PE before study launch who underwent diagnostic imaging and had a D-dimer level drawn were also evaluated. Results In this study, 17 patients were diagnosed with a PE and 42 patients had no PE on diagnostic imaging. Sixteen out of 17 patients with a PE versus 11 out of 42 without PE had an abnormal D-dimer level (p = 0.001). Four patients with a PE versus zero without a PE had an abnormal MWS (p = 0.005). The combination of a trimester-specific D-dimer level along with the MWS was abnormal in all 17 patients with a documented PE versus 11/42 (26.2%) patients without a documented PE (p = 0.001). Conclusion A combination of trimester-specific D-dimer levels along with a MWS can be used in pregnancy to triage women into a low-risk category for PE and thereby avoid radiation exposure in a majority of pregnant patients.

Patterns of fetal growth in an Asian Indian cohort in the USA.

OBJECTIVE: To determine whether a greater proportion of fetuses in an Asian Indian cohort are classified as small for gestational age than would be expected from a normally distributed population. METHODS: A retrospective analysis of fetal growth pattern and neonatal outcome was conducted among Asian Indian women who were referred to a maternal-fetal medicine center in Park Ridge, IL, USA, for evaluation of fetal growth between January 1, 2012, and December 31, 2013. The primary outcome was an abdominal circumference or estimated weight of lower than the 10th percentile for gestational age according to the Hadlock formula. RESULTS: Overall, 207 women and 210 fetuses were included. Forty-eight (22.9%) fetuses had an abdominal circumference lower than the 10th percentile. The total number of neonates classified as small for gestational age at delivery was 22 (10.5%), a value indicative of a normally distributed population. CONCLUSION: Fetal size was smaller than expected among the present Asian Indian cohort, but most neonates were classified as appropriate for gestational age at birth. Population specific growth curves are needed to improve assessment of fetal growth.

Fetal tachycardia treated successfully with maternally administered propylthiouracil.

Background. Fetal tachycardia may result from the transplacental passage of thyroid stimulating immunoglobulins in a patient with hypothyroidism secondary to ablation of Graves' disease. Case. A 32-year-old woman, gravida 4, para 2, and abortus 1, with hypothyroidism and a history of Graves' disease, presented at 23 6/7 weeks of gestation with a persistent fetal tachycardia. The treatment of the fetal tachycardia with maternally administered digoxin and Sotalol was unsuccessful. Maternal thyroid stimulating immunoglobulins were elevated, and treatment with maternally administered propylthiouracil (PTU) resulted in a normal sinus rhythm for the remainder of the pregnancy. An induction of labor was performed at 37 weeks. Four to five days after delivery, the neonate exhibited clinical signs of hyperthyroidism necessitating treatment. Conclusion. Fetal tachycardia resulting from the transplacental passage of thyroid stimulating immunoglobulins can be successfully treated with maternally administered PTU. The neonate needs to be followed up closely as clinical signs of hyperthyroidism may occur as thyroid stimulating immunoglobulins continue to circulate in the neonate, while the serum levels of PTU decline.

Ghrelin levels in cord blood from concordant and discordant twin pairs: association with birth weight and postnatal catch-up growth.

OBJECTIVE: To determine whether cord blood ghrelin levels in discordant and concordant twins predict postnatal catch-up growth. METHODS: After obtaining parental consent, cord blood samples were collected at delivery for total ghrelin analysis. Infant weight, length and head circumference were obtained at birth, 2, 4, and 6 months of age. Data points post-discharge were obtained from the pediatrician's office or via parent contact. Pearson correlation evaluated the relationship between cord blood ghrelin levels and postnatal catch-up growth. RESULTS: There was a statistically significant correlation between cord blood ghrelin levels and birth weight among concordant twins, but not among the discordant twins. Cord blood ghrelin levels did not predict postnatal growth at 6 months of age overall, but did so in the subset of monochorionic, discordant pairs. CONCLUSION: Cord blood ghrelin levels did not correlate overall with birth size or postnatal catch-up growth in concordant and discordant twin pairs, but did so in selected subsets. Further studies are needed.

A management strategy for fetal immune-mediated atrioventricular block.

INTRODUCTION: The purpose of this study is to describe an in utero management strategy for fetuses with immune-mediated 2° or 3° atrioventricular (AV) block. METHODS AND RESULTS: The management strategy as applied to 29 fetuses consisted of three parts. First, using fetal echocardiography and obstetrical ultrasound, we assessed fetal heart rate (FHR), heart failure, growth and a modified biophysical profile score (BPS) assessing fetal movement, breathing and tone. Second, we treated all fetuses with transplacental dexamethasone, adding terbutaline if the FHR was<56 bpm. Digoxin and/or intravenous immune globulin (IVIG) was added for progressive fetal heart failure. Third, we delivered fetuses by cesarean section for specific indications that included abnormal BPS, maternal/fetal conditions, progression of heart failure, or term pregnancy. We assessed perinatal survival, predictors of delivery and maternal/fetal complications in 29 fetuses with 3° (n=23) or 2° (n=6) AV block. There were no fetal deaths. In utero therapy included dexamethasone (n=29), terbutaline (n=13), digoxin (n=3) and/or IVIG (n=1). Delivery indications included term gestation (66%), fetal/maternal condition (14%), low BPS (10%) and progression of fetal heart failure (10%). An abnormal BPS correlated with urgent delivery. CONCLUSION: These results suggest that applying this specific management strategy that begins in utero can improve perinatal outcome of immune-mediated AV block.

Fetal bladder sagittal length: a simple monitor to assess normal and enlarged fetal bladder size, and forecast clinical outcome.

PURPOSE: We examined if the parameter of fetal bladder sagittal length (FBSL) could serve as a monitor of normative and enlarged fetal bladder size. MATERIALS AND METHODS: There were 76 consecutive cases examined between 1984 and 2000 that included measurement of fetal bladder size as FBSL and postnatal urological followup. Fetal images used to assess normal bladder size were derived from cases in which the bladder was normal on prenatal imaging and postnatal testing. An enlarged bladder was categorized as being greater than the 95% CI for a given gestational age (GA). The presence and extent of renal pelvic dilatation were also noted and correlated with FBSL. RESULTS: Measuring normal FBSL in 39 fetuses showed an exponential growth pattern (r = 0.76), which could be represented by the approximate linear formula FBSL = GA in weeks -5 (+/- 95% upper/lower CI = 7). An enlarged bladder was diagnosed in 37 fetuses. A dilated bladder in 9 fetuses, defined as FBSL greater than the 95% upper CI of normal (ie between GA + 2 and GA + 12), showed outcomes of posterior urethral valves, vesicoureteral reflux or a normal outcome. Megacystis in 28 fetuses, defined as FBSL greater than 10 mm larger than that of a dilated bladder (ie greater than GA + 12), showed additional outcomes of megacystis megaureter/vesicoureteral reflux or prune-belly syndrome. A normal outcome was significantly more likely in fetuses with a dilated bladder than in those with megacystis (p < or = 0.05). The incidence of azotemia in those with a dilated bladder or megacystis and pyelectasis was significantly lower than that in those with megacystis with hydronephrosis (p < or = 0.03). CONCLUSIONS: Postnatal diagnosis of fetuses that show an enlarged bladder is predicted based on whether the bladder is enlarged as a dilated bladder or megacystis and if the renal pelvis is enlarged as pyelectasis or hydronephrosis.

Single versus weekly courses of antenatal corticosteroids in preterm premature rupture of membranes.

OBJECTIVE: This study was performed to evaluate the efficacy of weekly courses of antenatal corticosteroids compared with a single course in women with preterm premature rupture of membranes (PROM). METHODS: A planned secondary analysis of women with preterm PROM who participated in a multicenter, randomized trial of weekly courses of antenatal corticosteroids versus single-course therapy was performed. After their first course of standard antenatal steroid therapy, administered between 24 to 32-6/7 weeks of gestation, consenting women were randomly assigned to receive betamethasone versus placebo injections weekly until 34-0/7 weeks of gestation. Maternal and neonatal morbidities were compared between the 2 groups. RESULTS: Of the 161 women with preterm PROM, 81 women were assigned to receive weekly courses of steroids and 80 to the single-course group. There were no significant differences in composite morbidity between the groups (27 [34.2%] of 81 patients versus 33 [41.8%] of 80 patients, P =.41). Chorioamnionitis was higher in patients who received weekly courses of antenatal steroids (39 [49.4%] of 81 patients versus 25 [31.7%] of 80 patients, P =.04). CONCLUSION: Weekly courses of antenatal steroids in women with preterm PROM did not improve neonatal outcomes beyond that achieved with single-course therapy and was associated with an increased risk of chorioamnionitis. Antenatal steroid therapy should not be routinely repeated in patients with preterm PROM. LEVEL OF EVIDENCE: I

Amiodarone therapy for drug-refractory fetal tachycardia.

BACKGROUND: Fetal tachycardia complicated by ventricular dysfunction and hydrops fetalis carries a significant risk of morbidity and mortality. Transplacental digoxin is effective therapy in a small percentage, but there is no consensus with regard to antiarrhythmic treatment if digoxin fails. This study evaluates the safety, efficacy, and outcome of amiodarone therapy for digoxin-refractory fetal tachycardia with heart failure. METHODS AND RESULTS: Fetuses with incessant tachycardia and either hydrops fetalis (n=24) or ventricular dysfunction (n=2) for whom digoxin monotherapy and secondary antiarrhythmic agents (n=13) were not effective were treated transplacentally with a loading dose of oral amiodarone for 2 to 7 days, followed by daily maintenance therapy for <1 to 15 weeks. Digoxin therapy was continued throughout gestation. Newborns were studied by transesophageal pacing or ECG monitoring to determine the mechanism of tachycardia. Three fetuses were delivered urgently in tachycardia during amiodarone loading, and 3 required additional antiarrhythmic agents for sustained cardioversion. Amiodarone or amiodarone combinations converted 14 of 15 (93%) with reentrant supraventricular tachycardia, 2 of 2 with ventricular or junctional ectopic tachycardia, and 3 of 9 (33%) with atrial flutter. Amiodarone-related adverse effects were transient in 5 infants and 8 mothers. Mean gestational age at delivery was 37 weeks, with 100% survival. CONCLUSIONS: Orally administered amiodarone is safe and effective treatment for drug-refractory fetal tachycardia, specifically reentrant supraventricular tachycardia, junctional ectopic, or ventricular tachycardia, even when accompanied by hydrops fetalis or ventricular dysfunction.

Intermittent airway obstruction and superior vena cava syndrome in a patient with an undiagnosed mediastinal mass after cesarean delivery.

Airway obstruction and cardiovascular collapse may follow the induction of general anesthesia in patients with mediastinal masses. We present a case in which a patient with a diagnosis of an upper gastrointestinal bleed presented for an emergency cesarean delivery. At the conclusion of surgery, the patient had complete airway obstruction during an upper gastrointestinal endoscopy. Patients may encounter airway compromise during instrumentation of the esophagus, and the presence of an intrathoracic mass should be included in the differential diagnosis of airway obstruction.

Factors associated with success of emergent second-trimester cerclage.

OBJECTIVE: To assess the factors associated with delivery greater than or equal to 28 weeks' gestation after placement of an emergent cerclage in women with singleton gestations. METHODS: All women who underwent emergent cerclage, defined as any cerclage placed between 16 and 24 6/7 weeks' gestation in response to documented cervical change on physical examination, at Northwestern Memorial Hospital from 1980 to 2000 were identified. Univariable and multivariable analyses were used to determine the factors most associated with achieving at least 28 weeks' gestation. RESULTS: One hundred sixteen women were eligible for analysis. Maternal age, race, and operative variables such as suture type and use of antibiotics were not associated with differences in the frequency of delivery at or after 28 weeks. Cerclage placement at or after 22 weeks' gestation increased the likelihood of reaching 28 weeks, whereas several cervical examination findings (dilatation greater than 3 cm, cervical length less than 0.5 cm, and membranes prolapsing beyond the external cervical os) as well as need for placement in a nullipara significantly reduced the likelihood of reaching 28 weeks. In multivariable analysis, nulliparity (odds ratio 0.31, 95% confidence interval 0.1, 0.8) and membranes prolapsing beyond the external cervical os (odds ratio 0.24, 95% confidence interval 0.1, 0.4) continued to be associated with delivery before 28 weeks, whereas cerclage placement at or after 22 weeks (odds ratio 3.2, 95% confidence interval 1.2, 8.6) increased the chance of achieving at least 28 weeks' gestation. CONCLUSION: Nulliparity, the presence of membranes prolapsing beyond the external cervical os, and gestational age less than 22 weeks at cerclage placement are associated with decreased chance of delivery at or after 28 weeks after emergent cerclage; these factors may be used to help counsel patients considering the procedure.

Antenatal detection of skeletal dysplasias.

OBJECTIVE: To assess the accuracy of the prenatal diagnosis of skeletal dysplasias. METHODS: All antenatally detected anomalies are coded in our ultrasound database, which is linked with a genetics database that includes outcomes. A final diagnosis is sought on the basis of radiographic studies, molecular testing, or both. Our ultrasound and genetics databases were queried for "skeletal dysplasias." All cases were reviewed specifically for the degree of bone shortening and other distinguishing characteristics on antenatal sonography. RESULTS: Thirty-seven cases of skeletal dysplasia were antenatally diagnosed over an 8-year period. Complete follow-up was available in 31 cases. The mean gestational age at diagnosis was 22.7 weeks (range, 14-32.3 weeks). Twenty-one cases were diagnosed before 24 weeks. A final diagnosis was obtained in 80% of cases. The antenatal diagnosis was correct in 20 (65%) of 31 cases. There were 2 false-positive diagnoses. Specific final diagnoses included thanatophoric dysplasia (8), osteogenesis imperfecta (6), Roberts syndrome (2), achondroplasia (3), Ellis-van Creveld syndrome (1), metaphyseal dysplasia (1), spondyloepiphyseal dysplasia (1), distal arthrogryposis (1), caudal regression (1), and glycogen storage disorder (1). The condition was correctly thought to be lethal in 16 of the fetuses on the basis of early severe long bone shortening (13), femur length-abdominal circumference ratio of less than 0.16 (12), hypoplastic thorax (10), marked bowing or fractures (4), short ribs (4), caudal regression (1), and cloverleaf skull (1). The ability to predict lethality was 100%. There were no false-positive findings with respect to lethality. CONCLUSIONS: Accurate antenatal diagnosis of skeletal dysplasias is problematic; in this series, only 20 of 31 cases were correctly diagnosed. However, the antenatal prediction of lethality was highly accurate. The most common predictors of lethal skeletal dysplasias included early and severe shortening of the long bones, femur length-abdominal circumference ratio of less than 0.16, hypoplastic thorax, and certain distinguishing characteristics.