Patrick M. Mullin

Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy.

Our objective was to examine whether delivery at 37 weeks of gestation alters adverse pregnancy outcomes in Latina patients with intrahepatic cholestasis of pregnancy (ICP). We conducted a retrospective chart review of Latina patients who delivered at our institution coded with ICP between 2000 and 2007. During this time period it was our practice to offer delivery to patients with ICP at 37 weeks of gestation. Subjects were classified into three groups according to total bile acid (TBA) concentration: < 20 micromol/L (mild ICP), > or = 20 micromol/L and < 40 micromol/L (moderate ICP), and > or = 40 micromol/L (severe ICP). Meconium passage was observed in no births in patients with mild IC, but was found in 18% of deliveries with moderate/severe ICP. The risk of meconium passage increased linearly, with a 19.7% increased risk for each 10 mumol/L increase in TBA concentration ( P = 0.001). There was no association with higher TBA concentration and other adverse outcomes. There was no difference in adverse outcomes between moderate and severe ICP. We concluded that in our Latina population with ICP, an association existed between meconium passage and moderate/severe ICP. Delivering at 37 weeks was associated with a low risk of adverse outcomes due to ICP among all patients, including those with higher TBA concentrations.

Prevention of pre-eclampsia with low-dose aspirin or vitamins C and E in women at high or low risk: a systematic review with meta-analysis

UNLABELLED The aim of this study is to review literature about the efficacy of low dose aspirin (LDA) and vitamins C/E (VCE) to prevent pre-eclampsia in women at high and low risk. Randomized clinical trials were included and stratified for high and low risk women. Inclusion criteria were: assignment of patients in treated or placebo groups, definition of pre-eclampsia according to the guidelines of the International Society for the Study of Hypertension in Pregnancy. Exclusion criteria were: omitting at least one of the inclusion criteria, trials involving women with pre-eclampsia at trial entry, studies investigating hypertensive disorders other than pre-eclampsia, prophylaxis of intrauterine growth restriction with low-dose aspirin or vitamins C/E, non-randomized studies and data reported in graphs or percentages. The incidence of pre-eclampsia, perinatal outcomes and adverse effects attributable to LDA and VCE were compared between treated women and placebo. Inter-studies heterogeneity was tested. P<0.05 was considered significant. pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated. PRISMA guidelines were followed. Fifteen studies were pooled. LDA did not decrease the incidence of pre-eclampsia in high-risk (396/5025 - 8% vs placebo: 464/5027 - 9%; P=0.05; OR: 0.72; 95% CI: 0.51-1.00) and low-risk (137/4939 - 3% vs placebo: 166/4962 - 3%; P=0.10; OR: 0.82; 95% CI: 0.65-1.04) women. Similarly, VCE did not reduce the incidence of pre-eclampsia in high-risk (VCE: 250/1744 - 14% vs placebo: 275/1741 - 16%; P=0.24; OR: 0.84; 95% CI: 0.63-1.12) and low-risk (VCE: 56/935 - 6% vs placebo 47/942 - 5%; P=0.57; OR: 1.20; 95% CI: 0.82-1.75) women. In high-risk women, other hypertensive disorders were more frequent in VCE (121/1692 - 7%) than placebo (79/1693 - 5%; P=0.002). Perinatal outcomes were not improved by LDA or VCE. CONCLUSION there is no evidence to support the administration of LDA or VCE to prevent pre-eclampsia.

Familial Aggregation of Hyperemesis Gravidarum

OBJECTIVE This study was undertaken to determine whether there is familial aggregation of hyperemesis gravidarum (HG), making it a disease amenable to genetic study. STUDY DESIGN Cases with severe nausea and vomiting in a singleton pregnancy treated with intravenous hydration and unaffected friend controls completed a survey regarding family history. RESULTS Sisters of women with HG have a significantly increased risk of having HG themselves (odds ratio, 17.3; P = .005). Cases have a significantly increased risk of having a mother with severe nausea and vomiting; 33% of cases reported an affected mother compared to 7.7% of controls (P < .0001). Cases reported a similar frequency of affected second-degree maternal and paternal relatives (18% maternal lineage, 23% paternal lineage). CONCLUSION There is familial aggregation of HG. This study provides strong evidence for a genetic component to HG. Identification of the predisposing gene(s) may determine the cause of this poorly understood disease of pregnancy.

Posttraumatic stress symptoms following pregnancy complicated by hyperemesis gravidarum

Abstract Objective. Hyperemesis gravidarum (HG) can be accompanied by severe physical and emotional distress. Most studies have focused on the physical and psychological stress associated with this condition during the affected pregnancy. This study explores posttraumatic stress symptoms (PTSS) and negative life outcomes following HG pregnancies. Methods. A total of 610 women (HG = 377 and control = 233) were recruited and completed an online survey. χ-square analyses were used to compare the HG and control groups on various life outcome variables. Results. Eighteen percent of women with HG reported full criteria PTSS (n = 68). Negative life outcomes regarding financial and marital status, career, as well as psychological and physical well-being differed significantly for the HG groups compared to the control group (0.001 < p < 0.05). Conclusions. PTSS is common following HG pregnancies and is associated with negative life outcomes including inability to breastfeed, marital problems, financial problems, and inability of self care.

Prenatal exposure to hyperemesis gravidarum linked to increased risk of psychological and behavioral disorders in adulthood

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, is characterized by long-term maternal stress, undernutrition and dehydration. While maternal stress and malnutrition of pregnancy are linked to poor neonatal outcome and associated with poor adult health, long-term outcome of fetal exposure to HG has never been explored. The purpose of this study is to determine whether long-term emotional and behavioral diagnoses may be associated with fetal exposure to HG. Emotional and behavioral diagnoses of adults born of a pregnancy complicated by HG were compared to diagnoses from non-exposed controls. Offspring exposed to HG in utero were significantly more likely to have a psychological and behavioral disorder (OR = 3.6, P < 0.0001) with diagnoses primarily of depression, bipolar disorder and anxiety. In utero exposure to HG may lead to increased risks of psychological and behavioral disorders in the offspring.

Risk factors, treatments, and outcomes associated with prolonged hyperemesis gravidarum

Objective: To identify factors associated with prolonged Hyperemesis Gravidarum (HG). Study Design: About 395 women completed a survey regarding pre-existing conditions, treatments and outcomes. Responses were compared using two-sided t-tests or the F-test. Results: Participants with prolonged HG are slightly younger and weigh more. Pre-existing factors associated with prolonged HG include allergies and a restrictive diet. Prolonged HG is associated with hematemesis, dizziness, fainting and antiemetic treatment. Following pregnancy, those with prolonged HG reported more posttraumatic stress, motion sickness, muscle weakness and infants with irritability, severe colic and growth restriction. Conclusion: Multiple pre-existing conditions and poor maternal and infant outcomes were associated with prolonged HG. The most significant condition prior to pregnancy was allergies suggesting a possible autoimmune component affecting duration of HG. In addition, the most significant lifestyle choice linked to prolonged HG was a restrictive diet. Future research is needed to determine whether a change in diet prior to pregnancy may lead to a shorter duration of HG and its associated outcomes.

Prevention, Management, and Outcomes of Macrosomia: A Systematic Review of Literature and Meta-analysis

&NA; Macrosomia represents an obstetric challenge, and when suspected, there is no general consensus as to whether expectant management, induction of labor, or elective cesarean delivery are the best option. This review article was aimed to discuss literature published in the last decade about the identification, management, and outcomes of macrosomia. The identification of macrosomia remains uncertain, mainly because of the high heterogeneity across studies because of different definitions of macrosomia, gestational age at time of assessment, and fetal weight formulas. With regard to management and outcomes of macrosomia, 12,212 macrosomic neonates can be pooled from 17 articles. Compared with neonates with normal birth weight, the odds ratio of emergency cesarean delivery increases from 1.92 (1.53–2.42) to 2.24 (1.42–3.56) and 5.20 (3.47–7.79) for macrosomia 4000 g or greater, 4500 g or greater, and 5000 g or greater, respectively. The odds ratios of shoulder dystocia are 7.18 (2.06–25.00), 7.33 (5.13–10.48), and 16.16 (7.62–34.26) for macrosomia 4000 g or greater, 4500 g or greater, and 5000 g or greater, respectively. Three birth traumas were reported after cesarean delivery. Perinatal mortality is similar between macrosomic and neonates with normal birth weight at each cutoff of macrosomia. Nonetheless, limitations of current literature, which are also discussed in this review, do not allow to drive definitive conclusion about the management of macrosomia. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this CME activity, physicians should be better able to determine the optimal mode of delivery for pregnant women whose fetuses may be macrosomic, identify the potential risks of adverse neonatal outcomes in macrosomic fetuses, and identify the limitations in the obstetric literature on macrosomia.

Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum.

OBJECTIVE The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. STUDY DESIGN This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. RESULTS Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p<0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p<0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p<0.0089). Poor outcomes were associated with early start of symptoms (p<0.019), and treatment with methylprednisolone (p<0.0217), promethazine (p<0.0386), and other antihistamines [diphenhydramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p<0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. CONCLUSION Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy.

Perioperative characteristics associated with preterm birth in twin-twin transfusion syndrome treated by laser surgery

OBJECTIVE To identify perioperative risk factors for preterm delivery (PTD) in laser-treated patients with twin-twin transfusion syndrome (TTTS). STUDY DESIGN Twin-twin transfusion syndrome patients who underwent laser surgery were followed prospectively. Univariate and multivariate analyses were performed to identify gestational and surgical characteristics associated with preterm delivery. RESULTS Of 318 eligible patients, the mean (SD) gestational age of delivery was 32.8 (4.2) weeks. The number of days from laser surgery to delivery had a bimodal distribution; group I delivered within 21 days and group II delivered after 21 days of surgery. Eighteen patients (5.7%) were in group I and demonstrated the following risk factors for delivery within 21 days: incomplete laser surgery suspected (odds ratio [OR], 11.14; P = .0106), preoperative subchorionic hematoma (OR, 7.92, P = .0361), preoperative cervical length <2.0 cm (OR, 4.71; P = .0117), and recipients maximum vertical pocket ≥14 cm (OR, 3.23; P = .0335). In group II, 92 of 300 patients (30.7%) delivered <32 weeks, and 25 (8.3%) delivered <28 weeks; multivariate logistic regression analyses identified 5 risk factors for delivery <32 weeks: incomplete laser surgery suspected (OR, 10.0; P = .0506); incidental septostomy (OR, 4.4; P = .0009); triplet gestation (OR, 2.6; P = .0689); postoperative membrane detachment (OR, 2.4; P = .0393); and nonposterior placental location (OR, 1.8; P = .0282). CONCLUSION Timing of delivery after laser for twin-twin transfusion syndrome has a bimodal distribution with distinct gestational and surgical risk factors. This information may be useful in counseling patients and in directing future avenues of research.

A comparison of obstetrical outcomes with labor induction agents used at term

Abstract Objective: To compare the obstetrical outcomes of term pregnancies induced with one of four commonly used labor induction agents. Methods: This is a retrospective cohort study of induced deliveries between 1 August 1995 and 31 December 2007 occurring at the Los Angeles County + University of Southern California Medical Center. Viable, singleton, term pregnancies undergoing induction were identified. Exclusion criteria included gestational age less than 37 weeks, previous cesarean delivery, breech presentation, stillbirth, premature rupture of membranes, and fetal anomaly. Induction methods studied were oxytocin, misoprostol, dinoprostone and Foley catheter. Our primary outcome was cesarean delivery rate among the four induction agents. Secondary outcomes included rate of failed induction, obstetrical complications, and immediate neonatal complications. Results: A total of 3707 women were included in the study (1486 nulliparous; 2221 multiparous). Outcomes were compared across induction methods using Chi-square Tests (Pearson or Fisher’s, as appropriate). Among the nulliparous patients, there was no statistical difference among the four induction agents with regards to cesarean delivery rate (p = 0.51), frequency of failed inductions (p = 0.49), the cesarean delivery frequency for “fetal distress” (p = 0.82) and five minute Apgar score <7 (p = 0.24). Among parous patients, the cesarean delivery rate varied significantly by induction method (p < 0.001), being lowest among those receiving misoprostol (10%). Those receiving oxytocin and transcervical Foley catheter had cesarean rates of 22%, followed by dinoprostone at 18%. The rate of failed inductions was 2% among those receiving misoprostol, compared to 7–8% among those in the other groups (p < 0.01). Although cases of “fetal distress” between the four induction agents was not significantly different amongst multipara women, the cesarean delivery indication for “fetal distress” was higher among multipara receiving misoprostol (p = 0.004). There was no difference among the different induction agents with regards to five minute Apgar <7 (p = 0.34). Conclusion: Among nulliparous women, all induction methods have similar rate of cesarean delivery. The use of misoprostol appears to be associated with a lower risk of cesarean birth among parous women induced at our institution.