Fetal lower urinary tract obstruction: What should we tell the prospective parents?

Fetal lower urinary tract obstruction (LUTO), which often results in marked perinatal morbidity and mortality, is caused by a heterogeneous group of anatomical defects that lead to blockage of the urethra. The classic prenatal presentation of LUTO includes megacystis with hydronephrosis. While mild forms of the disease can be associated with favorable outcomes, more severe disease commonly leads to dysplastic changes in the fetal kidneys, and ultimately oligohydramnios, which can result in secondary pulmonary hypoplasia and renal failure at birth. The aim of this review is to provide practitioners with a general overview of the diagnosis and treatment of LUTO based on disease severity, along with some points to consider when counseling prospective parents of fetuses with this condition.

Serial amnioinfusions for fetal pulmonary palliation in fetuses with renal failure.

Fetal lower urinary tract obstruction (LUTO) encompasses a heterogeneous group of congenital pathologies and generally results in oligohydramnios. Fetal intervention (e.g. vesicoamniotic shunting, fetal cystoscopy) has traditionally been reserved for cases with a favorable renal profile, while those with unfavorable renal function have been offered termination or expectant management with the latter leading to high incidence of marked pulmonary hypoplasia, neonatal morbidity and mortality. Here, we describe two cases, which were not candidates for traditional intervention based on abnormal fetal renal function, who elected to proceed with serial amnioinfusions for fetal pulmonary palliation to attenuate the risk of pulmonary hypoplasia.

Comparison between laparoscopically assisted and standard fetoscopic laser ablation in patients with anterior and posterior placentation in twin-twin transfusion syndrome: a single center study.

BACKGROUND: The objective of our study was to compare outcomes following laparoscopically assisted procedure (LAP group) with those seen following a standard approach used in patients with either an anterior placenta (SAP group) or posterior placenta (SPP group). METHOD: This was a retrospective review of all the cases of twin-twin transfusion syndrome treated in our fetal center from October 2011 to July 2013. Technical characteristics of the procedure, perinatal survival outcome, and maternal morbidity were compared. RESULTS: The laser procedure time was significantly longer in the SAP group (44 ± 10 min) in contrast with SPP (19.3 ± 13.9 min, p < 0.001) and LAP group (32 ± 11 min, p: 0.012). Preterm premature rupture of membranes (PPROM) before 32 and 34 weeks of pregnancy was significantly more common with LAP versus SAP and SPP (90 vs 33.3 and 70.8% for 32 weeks respectively, p: 0.015; 100 vs 50 and 79.1% for 34 weeks respectively, p: 0.021). In terms of maternal morbidity and neonatal outcome, there were no significant differences between the three groups. CONCLUSION: LAP may be useful in cases where SAP is not feasible. Despite the increased risk of PPROM with LAP, perinatal survival and maternal outcomes are similar to that seen in SAP and SPP patients.

Fetal Lower Urinary Tract Obstruction (LUTO): a practical review for providers.

Fetal lower urinary tract obstruction (LUTO) is a serious condition, which commonly results in marked perinatal morbidity and mortality. The characteristic prenatal presentation of LUTO includes an enlarged bladder with bilateral obstructive uropathy. While mild forms of the disease result in minimal clinical sequelae, the more severe forms commonly lead to oligohydramnios, dysplastic changes in the fetal kidneys, and ultimately result in secondary pulmonary hypoplasia. The aim of this review is to provide practitioners with a practical and concise overview of the presentation, evaluation, and treatment of LUTO.

Estimating risk factors for spontaneous preterm delivery in teen pregnancies.

PURPOSE: Our aim was to estimate the perinatal risk factors associated with spontaneous preterm birth in the teenage parturient. METHODS: In a cohort study of all nulliparous teen (≤18-year old) deliveries over a 4-year period at one institution, we identified all cases of spontaneous preterm birth as defined by non-indicated delivery prior to 37 weeks of gestation. Analysis was performed using Fisher's exact, Student t test and logistic regression modeling. RESULTS: Of the 650 included teen deliveries, 88 (14 %) cases of spontaneous preterm birth were identified. Teenage mothers with spontaneous preterm birth had a significantly lower body mass index (BMI) (27.2 ± 6.4 vs. 31.0 ± 6.2, p = 0.0001) and had lower gestational weight gain (14.4 ± 6.6 vs. 11.2 ± 5.0 kg, p = 0.0001) than those mothers with uncomplicated term births. In fact, a normal prepregnancy BMI (<25 kg/m(2)) placed the teen at elevated risk for spontaneous preterm birth (OR 3.35, 95 % CI 1.98-5.64), while prepregnancy obesity (30-35 kg/m(2)) was protective (OR 0.26, 95 % CI 0.12-0.58). Controlling for potential confounders such as race, tobacco or illicit drug use, late prenatal care and sexually transmitted infections did not attenuate the above findings. CONCLUSIONS: Higher prepregnancy BMI, especially obesity, appears to be protective against spontaneous preterm birth in the nulliparous teen parturient. Further studies confirming this finding and investigation of potential underlying mechanisms of this association are warranted.

Short-term neonatal outcomes in diamniotic twin pregnancies delivered after 32 weeks and indications of late preterm deliveries.

OBJECTIVE: We sought to compare neonatal outcomes in twin pregnancies following moderately preterm birth (MPTB), late preterm birth (LPTB), and term birth and determine the indications of LPTB. STUDY DESIGN: We performed a retrospective cohort study. MPTB was defined as delivery between 32(0/7) and 33(6/7) weeks and LPTB between 34(0/7) and 36(6/7) weeks. The composite neonatal adverse respiratory outcome was defined as respiratory distress syndrome and/or bronchopulmonary dysplasia. The composite neonatal adverse nonrespiratory outcome included early onset culture-proven sepsis, necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage, or periventricular leukomalacia. LPTB cases were categorized as spontaneous (noniatrogenic), evidence-based iatrogenic, and non-evidence-based (NEB) iatrogenic. RESULTS: Of the 747 twin deliveries during the study period, 453 sets met the inclusion criteria with 22.7% (n = 145) MPTB, 32.1% (n = 206) LPTB, and 15.9% (n = 102) term births. Compared with term neonates, the composite neonatal adverse respiratory outcome was increased following MPTB (relative risk [RR] 24; 95% confidence interval [CI] 3.0 to 193.6) and LPTB (RR 13.7; 95% CI 1.8 to 101.8). Compared with term neonates, the composite neonatal adverse nonrespiratory outcome was increased following MPTB (RR 22.3; 95% CI 3.9 to 127.8) and LPTB (RR 5.5; 95% CI 1.1 to 27.6). Spontaneous delivery of LPTB was 63.6% (n = 131/206) and the rate of iatrogenic delivery was 36.4% (n = 75/206). The majority, 66.6% (n = 50/75), of these iatrogenic deliveries were deemed NEB, giving a total of 24.2% (50/206) NEB deliveries in LPTB group. CONCLUSION: Our data demonstrate a high rate of late preterm birth among twin pregnancies, with over half of nonspontaneous early deliveries due to NEB indications. Although our morbidity data will be helpful to providers in counseling patients, our finding of high NEB indications underscores the need for systematic evaluation of indications for delivery in LPTB twin deliveries. Furthermore, this may lead to more effective LPTB rate reduction efforts.

Single-Access Fetal Endoscopy (SAFE) for myelomeningocele in sheep model I: amniotic carbon dioxide gas approach.

BACKGROUND: This study aimed to assess the feasibility of single-access fetal endoscopy (SAFE) for the management of myelomeningocele (MMC) using intrauterine carbon dioxide as a distension medium in a sheep model. METHODS: This prospective experimental case-control study investigated 12 lamb fetuses that had a myelomeningocele-like defect surgically created on the 75th day of gestation. Four fetuses remained untreated (control group), and eight fetuses had MMC repair using two fetoscopic approaches with carbon dioxide used to distend the amniotic cavity. A collagen patch was placed over the defect and secured with surgical sealant. Four animals had a two-port fetoscopic procedure, and four animals had SAFE. Clinical and pathologic studies were performed after delivery. RESULTS: This study confirmed the validity of the animal MMC model. None of the control animals was able to stand or walk, and all had a significant defect in the lumbar area with continuous leakage of cerebrospinal fluid, ventriculomegaly, and a Chiari-II malformation. All the treated animals, independently of the number of ports used in the repair, were able to walk and had a closed defect with resolution of the Chiari malformation. CONCLUSIONS: The SAFE patch and glue coverage of surgically created fetal MMC is feasible and effective in restoring gross neurologic function in the fetal lamb model.

Maternal morbidity and reproductive outcomes related to fetal surgery.

PURPOSE: The purpose of this manuscript was to examine the maternal morbidity and reproductive outcomes following maternal-fetal surgery with an emphasis on the EXIT procedure. METHODS: The medical records of all women who underwent an ex-utero intrapartum treatment (EXIT) procedure or mid-gestation open maternal fetal surgery (OMFS) at our center from December 2001 to December 2011 were reviewed retrospectively. Future reproductive outcomes were obtained via telephone questionnaire. RESULTS: Thirty-three women underwent maternal-fetal surgery. Twenty-six had EXIT, and seven had OMFS. The questionnaire response was 82% (27/33). Eighty-one percent (17/21) of the EXIT cohort desired future pregnancy. All who attempted (13/13) were successful. The majority (85%) conceived spontaneously and within 2.5 years on average. In the OMFS group, 40% experienced complications. One had uterine dehiscence, and another had uterine rupture requiring urgent delivery at 36 weeks. In subsequent pregnancies, 20% of OMFS cases were complicated by uterine rupture, and 8% of EXIT patients had uterine dehiscence. All had good maternal-fetal outcome. CONCLUSION: Future reproductive capacity and complication rates in subsequent pregnancies following EXIT procedure are similar to those seen in the general population. In contrast, mid-gestation OMFS remains associated with relatively morbid complications. This evidence can help guide in counseling expectant mothers who are faced with the challenge of considering fetal surgery.

Outcomes of fetuses with lower urinary tract obstruction treated with vesicoamniotic shunt: a single-institution experience.

PURPOSE: The purpose of this manuscript was to examine the outcomes of patients with lower urinary tract obstruction (LUTO) treated with vesicoamniotic shunt (VAS) to improve the quality of prenatal consultation and therapy. METHODS: The medical records of all patients diagnosed with LUTO at our center between January 2004 and March 2012 were reviewed retrospectively. RESULTS: Of 14 male fetuses with LUTO, all with characteristic ultrasound findings, 11 underwent intervention. One patient received vesicocentesis alone, while 10 had VAS. Two fetuses additionally underwent cystoscopy (one with attempted valve ablation), and two had peritoneoamniotic shunts. Of 16 total VAS, 13 were placed successfully, 8 dislodged (median 7 days), and 1 obstructed (84 days). Two fetuses suffered in utero demise, and two have unknown outcomes. LUTO was confirmed in six of eight live-born fetuses. One patient died in the neonatal period, while seven survived. All six available at follow-up (median 3.7 years), had significant genitourinary morbidity. Five patients had chronic kidney disease, but only one has required dialysis and transplant. Three had respiratory insufficiency, and one required a tracheostomy. CONCLUSION: Despite significant perinatal and long-term morbidity, VAS offers patients faced with a poor prognosis an improved chance of survival. Our results underscore the need for further research into the diagnosis and treatment of LUTO.

Do pregnant women with depression have a pro-inflammatory profile?

AIM: We tested the hypothesis that maternal depression is associated with a pro-inflammatory state in pregnancy. MATERIAL AND METHODS: In this nested case-control study, pro-inflammatory cytokine levels were compared between women with depression in pregnancy (n = 100) and a computer-generated referent group of healthy women known not to be depressed (n = 100). We only included cases with a documented Diagnostic and Statistical Manual of Mental Disorders depression diagnosis in the current pregnancy. Serum samples drawn at 11-14 weeks of gestation were analyzed for levels of tumor necrosis factor-alpha and interleukin-6 using high-sensitivity immunoassays. RESULTS: Maternal demographics were similar between the groups except for older age (34.1 vs 32.7 years, P = .05), and lower body mass index (27.3 vs 28.9 kg/m², P = 0.03) among the depressed subjects. Compared to control women, tumor necrosis factor-alpha (5.8 ± 3.4 vs 3.2 ± 2.8 pg/ml, P < 0.0001) and interleukin-6 (2.4 ± 3.8 vs 1.5 ± 1.4 pg/ml, P = 0.03) levels were higher among women with depression. The higher rate of inflammatory cytokines remained significant after controlling for potential confounders, including maternal age and body mass index. CONCLUSION: Women with depression may have higher levels of inflammatory markers in early pregnancy. Our findings support the hypothesis that inflammation may be a mediator in the association between maternal depression and adverse perinatal outcomes.

Midgestation maternal serum 25-hydroxyvitamin D level and soluble fms-like tyrosine kinase 1/placental growth factor ratio as predictors of severe preeclampsia.

Recent studies have shown that low serum 25-hydroxyvitamin D (25[OH]D) level is a risk factor for preeclampsia. The clinical significance of in vitro findings that vitamin D regulates vascular endothelial growth factor production is unclear. We sought to determine whether there is an association between midgestation serum 25(OH)D levels and angiogenic factor activity and to compare their predictive value for the development of severe preeclampsia. We conducted a nested case-control study of women with severe preeclampsia (n=41) versus women with uncomplicated term birth (n=123) who had second trimester genetic screening (15-20 weeks). Using banked frozen serum, we measured levels of 25(OH)D, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, and placental growth factor and compared their correlations and predictive values. We found no correlation between serum 25(OH)D and angiogenic factors levels. 25(OH)D alone was comparable to vascular endothelial growth factor and soluble fms-like tyrosine kinase 1/placental growth factor ratio as a predictive marker for severe preeclampsia. A composite of both 25(OH)D level and soluble fms-like tyrosine kinase 1/placental growth factor ratio was more predictive than either alone (area under curve: 0.83 versus 0.74 and 0.67, respectively). In conclusion, combining midpregnancy 25(OH)D level with soluble fms-like tyrosine kinase 1/placental growth factor ratio provides a better prediction for the development of severe preeclampsia.

Maternal depression and Epstein-Barr virus reactivation in early pregnancy.

OBJECTIVE: Recent evidence suggests a link between Epstein-Barr virus reactivation and chronic stress due to decreased cellular immune responses. Maternal depression complicates 10% to 20% of pregnancies and is accompanied by stress. We sought to estimate the association of Epstein-Barr virus reactivation with depression in pregnancy. METHODS: In this cohort study, prevalence of Epstein-Barr virus reactivation was compared between 100 pregnant women with depression before pregnancy and a computer-generated referent group of 100 healthy women not known to be depressed. We included only those women with documented Diagnostic and Statistical Manual of Mental Disorders depression diagnoses in the current pregnancy. Serum samples were analyzed for presence of Epstein-Barr virus viral capsid antigen, nuclear antigen, and early antigen antibodies. Epstein-Barr virus reactivation was defined by presence of viral capsid antigen or nuclear antigen immunoglobulin (Ig) G, along with early antigen IgG, viral capsid antigen IgM, or both early antigen IgG and viral capsid antigen IgM. RESULTS: Maternal demographics were similar between the groups except for older age (34.1 compared with 32.7 years, P=.05), and lower body mass index (27.3 compared with 28.9, P=.03) among the depressed individuals. Ninety-five percent of the women were seropositive for Epstein-Barr virus. Women with depression were more likely to have Epstein-Barr virus reactivation (48% compared with 30%, P=.01) when compared with referent participants. Epstein-Barr virus reactivation remained associated with maternal depression (adjusted odds ratio 1.97, 95% confidence interval 1.10-3.77, P=.03) after controlling for potential confounders. CONCLUSION: Women with depression have higher prevalence of Epstein-Barr virus reactivation, possibly due to increased stress. LEVEL OF EVIDENCE: II.

B cell acute lymphocytic leukemia in pregnancy.

Acute lymphocytic leukemia (ALL) is a rare occurrence in pregnancy and can be rapidly fatal if left untreated. The need for immediate treatment of ALL, coupled with the maternal-fetal risks from the chemotherapy regimen render a therapeutic dilemma in pregnant women with ALL. We report a case of ALL diagnosed in the 24th week of pregnancy to outline our management strategy, to demonstrate the feasibility of treatment with multi-agent chemotherapy, and to provide a review of the literature.

Prevalence of Epstein-Barr virus reactivation in pregnancy.

Recent evidence suggests a link between Epstein-Barr virus (EBV) reactivation and chronic stress in nonpregnant adults, possibly due to decreased cellular immune response. Our objective was to determine the prevalence of EBV seropositivity in a diverse cohort of pregnant women and whether maternal demographic characteristics were associated with EBV reactivation. In this cross-sectional study, we evaluated midpregnancy serum specimens from 64 healthy pregnant women for presence of EBV viral capsid antigen, EBV nuclear antigen, and EBV early antigen. The subjects were reported as EBV seronegative, EBV seropositive with reactivation, and EBV seropositive without reactivation. The maternal demographics of the seropositive women with EBV reactivation were compared with their nonreactivated counterparts. Chi-square and Student T test were used for statistical analysis. In our pregnant cohort, 63 (98%) of the 64 women were EBV seropositive. Among these seropositive women, 22 (35%) women demonstrated EBV reactivation in pregnancy. EBV reactivation was not associated with maternal age, race, parity, or insurance type. In our diverse pregnant cohort, 98% of women analyzed were EBV seropositive with 35% demonstrating EBV reactivation in the pregnancy by the second trimester. The pathophysiology and clinical implications of EBV reactivation during pregnancy need further study.

Deletion of hepatocyte nuclear factor-1-beta in an infant with prune belly syndrome.

Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-beta microdeletion. Hepatocyte nuclear factor-1-beta is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension.

Obstetric and newborn infant outcomes in human immunodeficiency virus-infected women who receive highly active antiretroviral therapy.

OBJECTIVE: Our aim was to examine perinatal outcomes in women who are infected with human immunodeficiency virus (HIV) and who receive highly active antiretroviral therapy compared with the general population. STUDY DESIGN: In this retrospective cohort study, we compared 151 HIV-positive and 302 HIV-negative women. We defined highly active antiretroviral therapy as concomitant use of at least 3 antiretroviral drugs. We calculated frequencies and odds ratios for adverse pregnancy outcomes. RESULTS: Compared with control subjects, smoking (odds ratio, 4.62; 95% confidence interval [CI], 2.58-8.27), drug abuse (odds ratio, 5.48; 95% CI, 2.21-13.59), and spontaneous preterm birth (adjusted odds ratio, 2.27; 95% CI, 1.22-4.25) were more common among HIV-positive women. HIV-positive women were more likely to deliver a small-for-gestational-age infant, but this was due to higher tobacco and cocaine use. Neonatal outcomes were otherwise similar. CONCLUSION: HIV-positive women are at increased risk for preterm birth and lower birthweight infants; therefore, antenatal surveillance should include fetal growth assessment. Highly active antiretroviral therapy use does not increase maternal complications.

Endometriosis mimicking ovarian cancer in the setting of acquired immune deficiency syndrome.

BACKGROUND: With rising rates of human immunodeficiency virus (HIV) among women and resultant immunosuppression, clinicians face varying presentations of gynecologic pathologies. We report a case of endometriosis in a patient with acquired immunodeficiency syndrome (AIDS) presenting with a Sister Mary Joseph's nodule and mimicking carcinomatosis. CASE: A woman with AIDS and 2-month history of abdominal pain, distention, and weight loss was found to have periumbilical and pelvic masses, ascites, lymphadenopathy, and an elevated CA 125 level. Operative findings included chocolate-colored ascites and peritoneal seeding involving the ovaries, uterus, appendix, bowel, umbilicus, and omentum. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and resection of all gross disease. Pathologic diagnosis was endometriosis and AIDS-associated adenopathy. COMMENT: Immunodeficiency from AIDS can affect the progression of endometriosis to the point of mimicking ovarian malignancy.