Transplacental Passage of Acetaminophen in Term Pregnancy.

Objective The objective of this study was to determine the maternal and fetal pharmacokinetic (PK) profiles of acetaminophen after administration of a therapeutic oral dose. Study Design After obtaining Institutional Review Board approval and their written informed consent, pregnant women were given a single oral dose (1,000 mg) of acetaminophen upon admission for scheduled cesarean delivery. Maternal venous blood and fetal cord blood were obtained at the time of delivery and acetaminophen levels were measured using gas chromatography-mass spectroscopy. PK parameters were calculated by noncompartmental analysis. Nonparametric correlation of maternal/fetal acetaminophen levels and PK curves were calculated. Results In this study, 34 subjects were enrolled (median, 32 years; range, 25-39 years). The median maternal weight was 82 kg (range, 62-100 kg). All but two subjects were delivered beyond 39 weeks' gestation. The median newborn birth weight was 3,590 g (interquartile range, 3,403-3,848 g). Noncompartmental analysis described similar PK parameters in the maternal (T1/2, 84 minutes; apparent clearance [Cl/F], 28.8 L/h; apparent volume of distribution [Vd/F], 57.5 L) and fetal compartments (T1/2, 82 minutes; Cl/F, 31.2 L/h; Vd/F, 61.2 L). Paired maternal/fetal acetaminophen levels were highly correlated (p < 0.0001). Conclusion Fetal acetaminophen PKs in the fetus parallels that in the mother suggesting that placental transfer is flow limited. Maternal acetaminophen levels can be used as a surrogate for fetal exposure.

Behavioural consequences of child abuse.

OBJECTIVE: To discuss the consequences of abuse on childhood behavioural development, to highlight some behavioural clues that might alert physicians to ongoing child abuse, and to explore the specific role of the family physician in this clinical situation. SOURCES OF INFORMATION: A systematic search was used to review relevant research, clinical review articles, and child protection agency websites. MAIN MESSAGE: A child's behaviour is an outward manifestation of inner stability and security. It is a lens through which the family physician can observe the development of the child throughout his or her life. All types of abuse are damaging to children-physically, emotionally, and psychologically-and can cause long-term difficulties with behaviour and mental health development. Family physicians need to be aware of and alert to the indicators of child abuse and neglect so that appropriate interventions can be provided to improve outcomes for those children. CONCLUSION: Child abuse might cause disordered psychological development and behaviour problems. Family physicians have an important role in recognizing behaviour clues that suggest child abuse and in providing help to protect children.

Resolution of complete placenta previa: does prior cesarean delivery matter?

OBJECTIVES: The purpose of this study was to prospectively assess the rate of resolution of complete placenta previa diagnosed at second-trimester sonography in patients with and without previous cesarean delivery. METHODS: This prospective study evaluated patients at 3 institutions with complete placenta previa diagnosed at second-trimester screening sonography. All patients were followed with sonography every 4 to 6 weeks until either resolution of the previa or delivery occurred. Patients with persistent/nonresolving complete placenta previa underwent cesarean delivery. RESULTS: A total of 67 patients were enrolled in the study; 18 patients had a prior cesarean delivery. Resolution of placenta previa occurred in 11 of 18 patients (61%) with a prior cesarean delivery, whereas 44 of 49 patients (90%) without a prior cesarean delivery had resolution of placenta previa (P = .012, Fisher exact test). Placental location per se (anterior or posterior) was not associated with resolution of placenta previa (P = .22). Complete placenta previa persisted to delivery in 5 of 9 patients (56%) with a prior cesarean delivery and an anterior placental location. CONCLUSIONS: This prospective study indicates that patients with a prior cesarean delivery and complete placenta previa diagnosed at second-trimester sonography are less likely to have subsequent resolution of the previa when compared to those without a history of cesarean delivery.

Transabdominal and transcervical chorionic villus sampling models to teach maternal-fetal medicine fellows.

OBJECTIVE: Many fellowship programs in maternal-fetal medicine (MFM) lack sufficient exposure and training in chorionic villus sampling (CVS). We describe a novel training model of transabdominal and transcervical CVS. METHODS: A porcine heart simulated a 12-week human uterus with a cervical canal created at the apex of the heart. A piglet was placed within a water-filled condom, which was placed inside the "uterus." A second water-filled condom simulated a maternal bladder. Fresh human placenta was placed between the condom and uterine wall. A zipper-sealed freezer bag with ultrasonic gel simulated an abdominal wall. Transabdominal ultrasound was utilized with this model to perform CVS. RESULTS: The design involved four MFM specialists and three fellows. Twenty-three faculty MFM specialists and eight MFM fellows endorsed the fidelity of both models. One hundred percent of attendees of a procedural workshop agreed that these models could be used to teach proper technique to fellows and faculty. CONCLUSION: We report a novel training model for transabdominal and transcervical CVS to teach proper technique in a nonclinical setting.

Current trends in narcotic use in pregnancy and neonatal outcomes.

OBJECTIVE: The purpose of this study was to evaluate trends and prevalence of chronic prescription narcotic use during pregnancy and the subsequent neonatal outcomes. STUDY DESIGN: We conducted a retrospective cohort study of all deliveries at Mayo Clinic from 1998 through 2009; the data was obtained from prospectively maintained obstetrics and neonatal databases. RESULTS: Over the study time period, there were 26,314 deliveries; 167 women used prescription narcotics chronically during pregnancy. The prevalence of women who used chronic narcotics during their pregnancy increased over the time period from 1998-2009 (P < .0001). Neonatal withdrawal syndrome occurred in 10 of neonates (5.6%), and all but 1 of these neonates required pharmacologic treatment for the disease. CONCLUSION: Chronic narcotic use during pregnancy is increasing in prevalence. Neonatal withdrawal syndrome occurred in 5.6% of the exposed neonates. Although neonatal withdrawal syndrome is uncommon, it is clinically significant. Physicians need to consider the risks and benefits carefully when prescribing narcotic pain medications during pregnancy.

Cost-effective standardization of preterm labor evaluation.

OBJECTIVE: The purpose of this study was to determine the effect of a standardized evidence-based protocol for preterm labor evaluation on resource use and obstetrics outcomes. STUDY DESIGN: We conducted a retrospective 12-month observational study of patients with symptoms of preterm labor at the Mayo Clinic. All patients underwent triage evaluation per a standardized protocol with a combination of cervical length measurement with contingent fetal fibronectin assay. RESULTS: Of 201 patients who underwent evaluation, 3 women delivered within 7 days, and only 1 woman delivered after a negative evaluation. Mean gestational age at evaluation was 29 weeks 1 day, and delivery was at 38 weeks 3 days of gestation, with an average interval of 57.4 days until delivery. The rate of hospital admission was reduced by 56%, compared with the previous year; an estimated annual cost saving was $39,900. CONCLUSION: Implementation of a standardized protocol for evaluation of preterm labor reduces the rate of unnecessary hospital admissions for observation with consequent significant reduction in expenses.

Malignant schwannoma in pregnancy: a case report and literature review.

Malignant peripheral nerve sheath tumors in pregnancy are an uncommon finding. This diagnosis in a pregnant patient with neurofibromatosis type 1 poses additional treatment dilemmas. A 28-year-old primigravida with known neurofibromatosis type 1 complained of increasing shortness of breath and cough. Evaluation revealed a large chest mass, biopsy proven to be a malignant schwannoma. This malignant peripheral nerve sheath tumor, discovered at 26 weeks' gestation, grew so rapidly that delivery was necessary at 30 weeks' gestation. Management of pregnant patients with rare, rapidly growing tumors may require early delivery in cases where maternal health is in jeopardy.

Pain associated with chorionic villus sampling: transabdominal vs transcervical approach.

OBJECTIVE: The purpose of this study was to compare anticipated and perceived pain that is associated with transabdominal and transcervical chorionic villus sampling (CVS). STUDY DESIGN: Women with singleton pregnancies who were undergoing CVS completed a preprocedure 0-10 visual analog scale (VAS; 0 = no pain, 10 = excruciating pain) for anticipated transabdominal and transcervical CVS-related pain. After the procedure, patients completed a VAS for perceived pain. RESULTS: One hundred twenty-one women underwent transabdominal (n = 98) or transcervical (n = 23) CVS. Anticipated pain was 4.5 +/- 2.0, which was similar in patients who ultimately underwent transabdominal (score, 4.6 +/- 3.8) or transcervical (score, 4.1 +/- 2.2) CVS. Postprocedure perceived pain was similar for transabdominal CVS in women with an abdominal wall thickness of <4 cm (score, 2.3 +/- 0.8) and transcervical CVS (score, 2.6 +/- 2.2) but was significantly greater for transabdominal CVS among women with an abdominal wall thickness of > or =4 cm (score, 5.6 +/- 1.2; P < .0001) and nulliparous women who had transcervical CVS (score, 4.3 +/- 2.1; P = .01). CONCLUSION: Transabdominal CVS is more painful in heavier women, and transcervical CVS is more painful in nulliparous women.

Sonographic findings in trisomy 9.

OBJECTIVE: The purpose of this study was to identify the most common prenatal sonographic findings in fetuses with complete trisomy 9. METHODS: A retrospective review of all cases of trisomy 9 at 5 participating institutions over a 15-year interval was conducted. Indications for referral and sonographic findings in each case were reviewed to identify characteristic fetal structural anomalies. RESULTS: Six cases of trisomy 9 are presented. Most patients were referred for abnormal sonographic findings on screening examinations (66%) or advanced maternal age (33%). Fetal heart defects and central nervous system malformations were the most frequent sonographic anomalies seen. CONCLUSIONS: Sonographic findings in trisomy 9 are similar to those found in other autosomal trisomies. Because trisomy 9 is uniformly lethal and is not included as part of the standard prenatal aneuploidy screening by fluorescence in situ hybridization analysis, clinicians should be cautious in counseling patients with structurally abnormal fetuses until the full karyotype is available.

Ultrasound findings in trisomy 22.

We sought to identify the characteristic sonographic findings of fetal trisomy 22 by performing a retrospective review of nine cases of fetal trisomy 22. All cases of chromosomal mosaicism were excluded, as were first-trimester losses. Indications for sonography, gestational age, and sonographically detected fetal anomalies were analyzed. The majority of patients were referred for advanced maternal age or abnormal ultrasound findings on screening exam. Oligohydramnios was the most common sonographic finding, present in 55% of affected fetuses. Intrauterine growth restriction and increased nuchal thickness were slightly less frequent.

Pregnancy complicated by triploidy: a comparison of the three karyotypes.

We evaluated triploid pregnancy to determine whether there are clinically important differences between the three karyotypes: 69,XXX, 69,XXY, and 69,XYY. Prospectively maintained cytogenetic databases at five tertiary care centers were retrospectively reviewed over a 10-year period to identify all triploid pregnancies. Targeted ultrasounds were reviewed to identify fetal and placental findings. Sonographic findings were compared by karyotype. There was a total of 549 triploid gestations; preimplantation genetic diagnosis (PGD) detected 413 triploid embryos, and the cytogenetic databases provided 136 clinical pregnancies with triploidy. In triploid embryos with PGD, the frequency of the 69,XYY karyotype was 8.7% (36/413), compared with 0.74% (1/136) during the first trimester of clinical pregnancies (p = 0.002). In clinical pregnancies, 60% (36/60) of 69,XXY fetuses survived the first trimester of development compared with 69% (52/75) of 69,XXX fetuses (p = NS). No clinically important differences were observed between 69,XXX and 69,XXY karyotypes in terms of type, number, or severity of fetal or placental anomalies. Gestations with a 69,XYY karyotype are found less frequently compared with gestations with a 69,XXX or 69,XXY karyotype. The decline in fetal survival of the 69,XYY triploid karyotype needs further investigation. There are significant abnormalities detected during prenatal sonography in most all clinically recognized cases of triploidy. Sonography cannot reliably distinguish between the 69,XXY and 69,XXX karyotypes.

Elevated expression of serine protease HtrA1 in preeclampsia and its role in trophoblast cell migration and invasion.

OBJECTIVE: Aberrant expression of developmentally regulated genes during placental development could affect fetal growth and contribute to preeclampsia. Expression of serine protease HtrA1 is developmentally regulated with the highest expression in decidua capsularis, compared with ectoplacental cone, and with the highest expression during later stages of pregnancy, compared with early stages. This study was designed to determine the expression of HtrA1 in placental tissues from control and preeclamptic pregnancies and to determine the effect of HtrA1 expression in trophoblast cell migration and invasion. STUDY DESIGN: HtrA1 expression was assessed by immunohistochemistry in placentas from gestational age-matched preeclamptic and control pregnancies. HtrA1 expression in extravillous trophoblast cells, HTR-8/SVneo, was assessed by immunoblotting and immunofluorescence microscopy. Finally, the effect of ectopic expression of HtrA1 on cell migration and invasion was determined in HTR-8/SVneo cells. RESULTS: Higher expression of HtrA1 was detected in placental tissues collected from patients with early-onset preeclampsia, compared with those from gestational age-matched control samples. Moreover, ectopic expression of HtrA1 significantly attenuates HTR-8/SVneo cell migration and invasion. CONCLUSION: Higher expression of HtrA1 is associated with early-onset preeclampsia and may affect trophoblast cell migration and invasion.

Anesthetic management of parturients with congenitally corrected transposition of the great arteries: three cases and a review of the literature.

Women with congenitally corrected transposition of the great arteries (CCTGA) have a propensity for congestive heart failure and cardiac dysrhythmias during pregnancy, labor, and delivery. We report the successful obstetric and anesthetic management of three women with CCTGA, review the pertinent medical literature, and discuss important issues surrounding the anesthetic management of parturients with CCTGA.

Dilation and evacuation of a single fetus after midtrimester PROM in previable twin pregnancy.

Midtrimester premature rupture of membranes (PROM) is an unusual complication of multiple gestation that most often results in poor obstetric outcome. Presented are four cases of twin pregnancy complicated by preterm PROM and umbilical cord prolapse at 16 to 21 weeks' gestation. After a period of expectant management, dilation and evacuation of only the presenting fetus was performed with careful ultrasound guidance, to attempt delayed interval delivery. This resulted in pregnancy prolongation of 42 to 133 days for the remaining cotwins. Dilation and evacuation of a single demised fetus in twin pregnancy complicated by PROM and cord prolapse can be accomplished with favorable clinical outcome.

Expectant management of uterine incarceration from an anterior uterine myoma: a case report.

BACKGROUND: Uterine incarceration is an infrequent complication of pregnancy in the early second trimester. Although imaging can be confirmatory, the diagnosis is made primarily on clinical grounds, and definitive treatment involves manual reduction to restore the proper anatomic position. Except for preexisting uterine retroversion, often this event is idiopathic. CASE: A 30-year-old primigravida presented at 15 weeks' gestation with uterine incarceration. Manual replacement was unsuccessful. Spontaneous resolution occurred at 20 weeks, followed by uneventful pregnancy. The patient underwent a classical cesarean section at term due to fetal malpresentation. CONCLUSION: Uterine incarceration may be managed conservatively, with a favorable outcome.

Experiences of substance-using suicidal males who present frequently to the emergency department.

OBJECTIVE: This qualitative study investigated the repeated use of the emergency department (ED) by men with a history of suicidal behaviour and substance abuse to understand the needs and barriers to care for this high-risk group. Identification of common themes from interviews with patients and health care workers can serve as a basis for improved ED-based interventions. METHODS: Using semistructured interviews, patients, ED staff and family physicians were asked about needs of the aformentioned group. Twenty-five patients were interviewed and completed questionnaires regarding their substance use, aggression, parasuicidal behaviour, alexithymia and childhood trauma. In addition, 27 staff members were interviewed. Interviews were tape-recorded, transcribed and qualitatively analyzed using an iterative coding process. RESULTS: Of the 25 patients, 23 (96%) had a mood or anxiety disorder and 18 (75%) had borderline personality disorder. One-half of the patients scored high and another quarter scored moderate on alexithymia testing. The ED was viewed as a last resort despite seeking help. Frustration was felt by both patients and staff regarding difficult communication, especially during an acute crisis. CONCLUSION: The ED plays an important role in the provision of care for men with recurrent suicidal behaviour and substance abuse. Some of the diagnoses and problems faced by these patients are beyond the purview of the ED; however, staff can identify mutual goals for crisis interventions, allow for frequent communication and seek to de-escalate situations through the validation of the stress patients are experiencing.

The 18-month well-child visit in primary care: Clinical strategies for early intervention.

Family physicians, paediatricians, nurse practitioners and all primary health care providers are well-positioned in the health care system to provide identification and intervention for developmental delay in early childhood. This can be accomplished through the promotion of healthy child development by supporting children and their parents, paying special attention to issues of attachment and parent-child interactions. Early recognition and intervention is critical for addressing all developmental, social and behavioural problems in young children. A familiarity with local community resources and services is crucial; it will assist primary health care providers in supporting families by providing extra assistance and assessment for families at risk. The present article reports on the evidence-based interventions at the 18-month visit including screening tools, resources and a case example. The importance of interdisciplinary coordination to provide a comprehensive approach to screening, assessment and intervention for developmental delays in infants and young children is highlighted.

Urinary podocyte excretion as a marker for preeclampsia.

OBJECTIVE: The objective of this study was to examine whether podocyturia, which is the urinary excretion of viable podocytes (glomerular epithelial cells), is present in urinary sediments of patients with preeclampsia. We also aimed to compare the test characteristics of podocyturia to those angiogenic factors that have been shown to play an important role in the pathogenesis of preeclampsia (s-Flt-1, PlGF, and endoglin). STUDY DESIGN: Serum angiogenic factors were measured in 44 patients with preeclampsia and 23 normotensive control patients. In a patient subset (15 cases and 16 control patients), urinary proteinuria were identified and quantified on the basis of their expressions of podocyte-specific proteins. RESULTS: Urinary podocyte excretion occurred in all patients with preeclampsia. The positive predictive value for the diagnosis of preeclampsia was greater for podocyturia than for any of the measured angiogenic factors. CONCLUSION: Podocyturia is a highly sensitive and specific marker for preeclampsia. It may contribute to the development of proteinuria in preeclampsia.

In utero losartan withdrawal and subsequent development of fetal inferior vena cava thrombosis.

BACKGROUND: Angiotensin receptor blockers are antihypertensive medications prescribed by a wide variety of physicians, especially for patients with coexistent diabetes mellitus. Angiotensin receptor blockers, as well as angiotensin-converting enzyme inhibitors, are contraindicated in pregnancy. CASE: We describe the reversal of losartan-induced oligohydramnios at 27 weeks of gestation with subsequent development of fetal thrombosis and possible mechanism of action for this extremely rare in utero complication. CONCLUSION: This theory may help explain the fetal stillbirths in women taking this class of medications during the second and third trimester of pregnancy.

Adverse outcomes of renovascular hypertension during pregnancy.

BACKGROUND: A 26-year-old primigravida, with no history of hypertension, presented at 20 weeks of gestation with severe pre-eclampsia. A pelvic ultrasound revealed intrauterine fetal death, probably caused by placental abruption. The pregnancy was terminated by induction with oxytocin, followed by a vaginal breech delivery. The patient remained hypertensive for 8 weeks after delivery. INVESTIGATIONS: Physical examination, laboratory investigation, renal angiogram and renal-vein renin sampling. DIAGNOSIS: An atrophic right kidney secondary to an occluded right renal artery, probably caused by dissected fibromuscular dysplasia; a contralateral high-grade stenosis secondary to fibromuscular dysplasia. MANAGEMENT: Right nephrectomy and angioplasty of the left renal artery.