Determinant of Prenatal Diagnostic Testing among Women with Increased Risk of Fetal Aneuploidy and Genetic Disorders.

OBJECTIVE: This study aimed to assess factors that influence patients' decisions in accepting prenatal diagnostic testing following genetic counseling for increased risk of fetal aneuploidy. METHODS: This is a retrospective cohort study of women at increased risk of fetal aneuploidy and genetic disorders who had genetic counseling from January 2012 to December 2016 at a single academic center. Demographics, indications for genetic counseling, and rates of diagnostic testing were collected and compared between those who accepted diagnostic testing and those who chose cell free DNA. The variables were analyzed using Chi-square, Fisher's exact test, and multiple logistic regression. RESULT: Of the 2,373 pregnant women who underwent genetic counseling for increased risk of fetal aneuploidy and genetic disorders during the study period, 321 women had diagnostic testing (13.5%). Women at 35 years and older accepted diagnostic testing more than women younger than 35 years (20.7 vs. 11.5%, p < 0.001). Asian women accepted diagnostic testing at 27.7% more than white, non-Hispanic Black, and Hispanic women at 18.0, 12.1, and 11.7%, respectively, p = 0.002. Number of indications for genetic counseling influenced the likelihood of accepting diagnostic testing. Women with one indication had 11.5% acceptance of diagnostic testing, and with two and three indications, it was 17.0 and 29.2%, respectively. The commonest indication for diagnostic testing was cystic hygroma (risk ratio [RR] = 7.5, 95% confidence interval [CI]: 3.12-8.76 p < 0.001). The relative risk of diagnostic testing for fetuses with shortened long bones, femur and humerus, thickened nuchal fold, echogenic bowel, single umbilical artery, and increased nuchal translucency were 4.0, 3.3, 3.1, 2.7, and 2.7, respectively. Abnormal serum analyte alone was associated with less acceptance of diagnostic testing (RR = 0.8, 95% CI: 0.7-0.96, p = 0.017). CONCLUSION: Age, race, ethnicity, and cumulative number of indications for genetic counseling influenced acceptance of diagnostic testing in at-risk women of fetal aneuploidy and genetic disorders. KEY POINTS: · Genetic counseling.. · Fetal aneuploidy.. · Genetic disorders.. · Prenatal diagnostic testing. Prenatal diagnostic testing in women with increased risk of fetal aneuploidy and genetic disorders..

Comparison of Continuation of Low-Molecular-Weight Heparin versus Switching to Unfractionated Heparin in the Peripartum.

OBJECTIVE: This study aimed to determine whether switching from low-molecular-weight heparin (LMWH) to unfractionated heparin (UFH) or its continuation in the peripartum affected anesthesia choice or bleeding complications. STUDY DESIGN: A retrospective cohort study of 189 anticoagulated pregnant women who delivered at the University of Illinois at Chicago Hospital and Health Science System from 2005 to 2016. Demography, anesthesia choice, and bleeding complications were compared between the two groups. RESULTS: There were 138 (73%) women on LMWH versus 51 (27%) who switched from LMWH to UFH during the peripartum. The demographics were similar, 123 women were on prophylactic: 81 (66%) were on LMWH and 42 (34%) switched to UFH. Of the 66 women on therapeutic anticoagulation, 57 (86%) continued on LMWH, while 9 (14%) switched to UFH. No difference in neuraxial anesthesia type received: 42 (82.4%) versus 108 (79.7%) women (odds ratio: 1.20, 95% confidence interval [CI]: 0.52-2.73, p = 0.837). Bleeding complications more than 1,000 mL, 6 versus 10% (relative risk [RR]: 0.58, 95% CI: 0.17-1.94, p = 0.380) and relaparotomy due to hemoperitoneum, 2% in either group (RR: 0.9, 95% CI: 0.10-8.48, p = 0.930) were similar in the two groups regardless of time of last injection. CONCLUSION: Anesthesia type and rate of bleeding complications were similar between women on LMWH and UFH during the peripartum.

Cervical cerclage for singleton pregnant patients on vaginal progesterone with progressive cervical shortening.

BACKGROUND: Premature cervical ripening plays a significant role in spontaneous preterm birth. Vaginal progesterone is the recommended treatment in singleton pregnancy with incidental short cervix. There is lack of evidence on whether it is beneficial to reinforce the cervix with cerclage when the cervical length becomes progressively shortened <10 mm while on vaginal progesterone. OBJECTIVE: Our aims are to determine whether cerclage with vaginal progesterone will: (1) reduce the overall spontaneous preterm birth rate, (2) prolong pregnancy latency, and (3) improve neonatal outcomes compared to vaginal progesterone alone. STUDY DESIGN: This was a retrospective cohort study at the University of Illinois at Chicago of all women with singleton pregnancy on vaginal progesterone for incidental short cervix, cervical length <20 mm. Only those with progressive cervical length shortening <10 mm who delivered at the University of Illinois at Chicago from January 2013 through December 2016 were included. The decision to perform cerclage was based on individual physician preference. Demographic data; information on serial cervical length status; medical, obstetric, and social history; cerclage vs no cerclage; and neonatal outcomes were compared. RESULTS: A total of 310 women with incidental short cervix on vaginal progesterone were identified, and of these, 75 had progressive shortening cervical length <10 mm and met inclusion criteria. Among the women with extremely shortened cervical length <10 mm, 36 women (48%) had cervical cerclage plus vaginal progesterone, and 39 women (52%) continued on vaginal progesterone alone. The baseline characteristics, mean cervical length (5.06 vs 5.52 mm), and mean gestational age at diagnosis of extreme short cervix (21.5 vs 21.3 weeks) were similar between women who received cerclage vs those who did not, respectively. The mean gestational age at delivery was significantly greater for those with cerclage (34 weeks and 3 days vs 27 weeks and 2 days; P < .001). The rate of spontaneous preterm birth at <37, 35, 32, 28, and 24 weeks were significantly lower in the cerclage group: 44.1% vs 84.2%, 38.2% vs 81.6%, 23.5% vs 78.9%, 14.7% vs 63.2%, and 11.8% vs 39.5%, respectively. The rate of spontaneous preterm birth <37 weeks remained significant after controlling for confounders (relative risk, 0.11; 95% confidence interval, 0.03-0.41; P < .001). The average pregnancy latency was 14 weeks in the cerclage combined with vaginal progesterone group compared to vaginal progesterone alone group. Neonatal intensive care unit admission and development of respiratory distress syndrome were significantly lower in the cerclage group compared to vaginal progesterone alone group: 13 (36.1%) vs 23 (65.7%) (relative risk, 0.55; 95% confidence interval, 0.34-0.90; P = .018) and 8 (22.2%) vs 17 (43.6%) (relative risk, 0.59; 95% confidence interval, 0.29-0.90; P = .027), respectively. Neonates of women with cerclage were also significantly less likely to develop necrotizing enterocolitis or experience neonatal death. CONCLUSION: Our study showed that cerclage plus vaginal progesterone in women with extremely shortened cervix significantly decreased overall spontaneous preterm birth rates, prolonged pregnancy latency by 2-fold, and decreased the overall neonatal morbidity and mortality.

Morbidity associated with the use of Foley balloon for cervical ripening in women with prior cesarean delivery.

OBJECTIVE: We evaluated the morbidity of Foley balloon for cervical ripening in comparison to oxytocin alone in women with a prior cesarean delivery. STUDY DESIGN: A four-hospital retrospective review of all women with viable singleton pregnancies and history of a single prior cesarean delivery presenting for cervical ripening between 1994 and 2015. Exposure groups were either Foley balloon or oxytocin, at the treating physician's discretion. The primary outcome was defined as maternal morbidity, evaluated by a composite that included hemorrhage, and/or uterine infection, and/or uterine rupture. We defined two secondary outcomes: neonatal morbidity, and vaginal delivery rate. Neonatal morbidity was evaluated by a composite that included five-minute APGAR score <7 and/or NICU admission. We adjusted results for potential confounding variables, including hospital site, maternal age and race, initial cervical dilation, and gestational age at delivery. RESULTS: We identified 688 patients who received ripening, 276 by Foley balloon and 412 by oxytocin. There was no significant difference in the primary outcome of maternal morbidity between groups: 38 (13.8%) in the Foley balloon group and 79 (19.2%) in the oxytocin group (aOR 1.43; 95% CI, 0.90-2.27). There was no significant difference in the secondary outcome of neonatal morbidity: 31 (11.3%) in the Foley balloon group and 51 (12.4%) in the oxytocin group (aOR 1.02; 95% CI, 0.57-1.80). The rate of vaginal delivery was significantly less in the Foley balloon group compared to the oxytocin group: 56.2% vs 64.1%, p = .037. CONCLUSION: When cervical ripening with either Foley balloon or oxytocin was utilized at the physician's discretion in women with prior cesarean, there was no identified difference in maternal and neonatal morbidity, but the rate of successful vaginal delivery was lower.

Assessing preventability for obstetric hemorrhage.

We sought to determine preventability for cases of obstetric hemorrhage, identify preventable factors, and compare differences between levels of hospital. We retrospectively reviewed a 1-year cohort of severe and near-miss obstetric hemorrhage in an urban perinatal network. An expert panel, using a validated preventability model, reviewed all cases. Preventability and distribution of preventability factors were compared between levels of hospital care. Sixty-three severe and near-miss obstetric hemorrhage cases were identified from 11 hospitals; 54% were deemed potentially preventable. Overall preventability was not statistically different by level of hospital, and 88% were provider related. The only treatment-related preventability factors were significantly different between levels of hospital and significantly less common in level III hospitals (p < 0.01). The majority of obstetric hemorrhage was preventable. The most common potentially preventable factor was provider treatment error, and this was significantly more common in level II hospitals. New interventions should be focused on decreasing providers' treatment errors.

Two cases of focal status epilepticus in pregnancy.

The management of women with epilepsy (WWE) presents many challenges for physicians. The primary goal during pregnancy is to achieve the best possible control of seizures with the least adverse effects associated with exposure to antiseizure medications (ASMs). Even though the guidelines for managing pregnant WWE are expanding, no definitive guidelines exist for the treatment of status epilepticus (SE). Additionally, much of our data comes from the effect of generalized tonic clonic seizures on the fetus. There is very little data on the effect of focal seizures and even less on focal SE. Here we present two cases of pregnant WWE who presented in focal SE, who underwent simultaneous video-EEG monitoring and fetal heart tracing (FHT). During each focal seizure the FHT demonstrated a normal baseline heart rate with moderate variability. In the second case due to continuous seizures more aggressive treatment had to be started. This led to maternal relative autonomic instability as well as absent variability on FHT. These findings raise many questions on the management of focal SE during pregnancy including if the effect of treatment is worse than the seizures, and how do we balance our goals for both mother and fetus?

Betamethasone in pregnancy: influence of maternal body weight and multiple gestation on pharmacokinetics.

OBJECTIVE: The goals of the study were to estimate the pharmacokinetic parameters of standard dose betamethasone in a large obstetrics population and evaluate the effect of maternal body size and multiple gestation on the pharmacokinetic parameters and their observed variability. STUDY DESIGN: This was a prospective pharmacokinetic study. Liquid chromatography mass spectrometry was used to measure betamethasone plasma concentrations. Pharmacokinetic parameters and significant clinical covariates were estimated with mixed effect modeling. Bootstrap analysis confirmed validity of the model. RESULTS: Two hundred seventy-four blood samples from 77 patients were obtained. The greatest effect on pharmacokinetic variability was observed with maternal lean body weight (LBW). The relationship between the pharmacokinetic parameters and LBW remained linear over a wide range of maternal body sizes. Multiple gestations did not affect the pharmacokinetic parameters. CONCLUSION: Individualization of betamethasone dosing by maternal LBW reduces variability in drug exposure. Mutiple gestations do not require betamethasone dosing adjustment, because pharmacokinetics are the same as singleton gestations.

Pearls in clinical obstetrics: challenges in anticoagulation in pregnancy.

Women are at increased risk for venous thromboembolism (VTE) during both pregnancy and in the post-partum period. We have conducted a comprehensive literature review of the use of anticoagulation in pregnancy for pregnant women at increased risk for VTE. Multiple factors, including physiologic and pharmacokinetic changes make the treatment and prevention of VTE complicated in pregnancy. Adequate treatment and prevention of VTE in pregnancy is critically important, yet good quality medical studies continue to be lacking. There is a growing amount of data for the use of low molecular weight heparin (LMWH) in pregnant women and this remains the treatment of choice in most indications. For both prophylactic and therapeutic treatments, when LMWHs are chosen, monitoring of antifactor Xa level, although controversial, is advised. Women with prosthetic valve who become pregnant face challenges in regard of type of anticoagulation, dosing and monitoring during pregnancy. Delivery options and peripartum care should be defined with a multidisciplinary approach and taking patient's preference and autonomy in consideration. More high-quality research on this topic is needed to guide the clinical care of this unique population.

A Case of Massive Hepatic Infarction in a Patient with HELLP Syndrome.

Background Hepatic infarction is an exceedingly rare complication of hemolysis, elevated liver enzymes, and low platelets syndrome. Few cases have been described in the medical literature and the true incidence remains unknown. It can lead to fulminant liver failure, liver transplant, or death if not promptly addressed. Case Report A 22-year-old primigravida presented with right upper quadrant and epigastric pain at 28 weeks' gestation. She had severely elevated blood pressures requiring intravenous antihypertensives as well as proteinuria, thrombocytopenia, and mild transaminitis. Within 6 hours of admission, her rapidly rising liver function tests (LFTs) necessitated urgent delivery by primary cesarean section. Her liver enzymes continued to rapidly worsen postoperatively and immediate postpartum computed tomography of the abdomen and pelvis revealed massive hepatic infarction, 11 × 10 × 15 cm, of the right lobe of the liver. Her transaminases peaked at alanine transferase of 2,863 IU/L and aspartate transferase of 2,732 IU/L. She received supportive multidisciplinary intensive care, and LFTs returned to normal by postoperative day 20. Conclusion Hepatic infarction is an extraordinarily rare complication of pre-eclampsia. Early recognition and prompt multidisciplinary management are vital to prevent catastrophic bleeding, hepatic failure, and death.

Pharmacokinetics of 17 alpha hydroxyprogesterone caproate in singleton pregnancy and its influence of maternal body size measures.

BACKGROUND: Reducing spontaneous preterm deliveries is a worldwide public health priority. Although many interventions have been studied, 1 of the most effective treatments to decrease recurrent preterm birth is the use of weekly 17 alpha hydroxy progesterone caproate. Previous studies on the influence of excessive adipose tissue and obesity on the use of 17 alpha hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm deliveries have shown conflicting findings. OBJECTIVE: To estimate the pharmacokinetics of weekly17 alpha hydroxyprogesterone caproate in singleton and to evaluate the effect of maternal body size on the pharmacokinetics parameters. STUDY DESIGN: A prospective, open-label, longitudinal design was implemented for this population pharmacokinetic study. Plasma samples and clinical variables were collected in pregnant women between 16 and 36 weeks' gestational age, carrying a singleton pregnancy and receiving 17 alpha hydroxyprogesterone caproate, 250 mg intramuscularly weekly for the prevention of recurrent spontaneous preterm birth. Pharmacokinetics parameters and significant clinical covariates were estimated using mixed effect modeling. Four body size indicators were used in the model to predict pharmacokinetics parameters: lean body weight, total body weight, body mass index, and body surface area. RESULTS: A total of 56 pregnant women, aged 18-44 years with body mass index of 14.5-54.6 kg/m2, provided 114 17 alpha hydroxyprogesterone caproate plasma samples concentration for analysis. A 1-compartment model with first-order absorption satisfactorily described 17 alpha hydroxyprogesterone caproate pharmacokinetics. Compared to other body size indicators, lean body weight best explained intersubject variability. Age, race, and gestational age did not influence 17 alpha hydroxyprogesterone caproate pharmacokinetics. Lean body weight was the best descriptor for the influence of body size on 17 alpha hydroxyprogesterone caproate apparent clearance. Simulations showed that administration of a standard fixed dose of 250 mg intramuscularly produced substantially lower 17 alpha hydroxyprogesterone caproate plasma concentrations in pregnant women with body mass index >30 kg/m2 compared to those with body mass index <30 kg/m2. Conversely, adjustment of the standard dose for differences in total body weight among women resulted in markedly higher 17 alpha hydroxyprogesterone caproate concentrations in women with body mass index >30 kg/m2 compared to women with lower body mass index. Administration of doses adjusted for lean body weight produced nearly identical 117 alpha hydroxyprogesterone caproate plasma concentrations in both the low- and high-body mass index groups. CONCLUSION: Population pharmacokinetics analysis indicates the clearance significantly increases with increasing lean body mass. Higher 17 alpha hydroxyprogesterone caproate doses, adjusted by maternal lean body mass, may be required in patients with a body mass index >30 to achieve equivalent plasma concentrations in pregnant women with a body mass index <30. Adjustment of 17 alpha hydroxyprogesterone caproate doses for lean body weight produces equivalent systemic 17 alpha hydroxyprogesterone caproate exposure in pregnant women regardless of body size.