Predictive factors for survival in patients with oligohydramnios secondary to antenatal kidney disease.

BACKGROUND: Renal oligohydramnios (ROH) is caused by bilateral congenital abnormalities, either of renal parenchymal or obstructive origin. ROH is a poor prognostic factor of neonatal survival; lung hypoplasia is reported to be the main cause of mortality. We aimed to describe the fetal morbidity and pre- and postnatal mortality in case of ROH due to renal congenital pathologies and to find predictive risk factors for morbidity and mortality. METHODS: All data were collected in Trousseau Hospital in the obstetric, neonatology, and pediatric nephrology units, from 2008 to 2020. RESULTS: We included 66 fetuses with renal parenchymal pathologies posterior urethral valves (PUV) (N = 25), bilateral kidney agenesis (N = 10), hypodysplasia (N = 16), and polycystic kidney disease (N = 10) causing oligohydramnios identified on antenatal ultrasound. Total pre- and postnatal mortality was 76% (50/66). Mortality, excepting termination of pregnancy (TOP), was 65%. The presence of pneumomediastinum and pneumothorax was not different in survivors and non-survivors. Fetuses with kidneys having features of hypodysplasia on ultrasound at T2 and those with oligohydramnios before 32 weeks GA had a higher risk of death. There was a significant difference in plasma creatinine of the surviving patients compared to the deceased patients, from day 3 onwards (183 µmol/L [88; 255] vs. 295 µmol/L [247; 326]; p = 0.038). CONCLUSIONS: The main differences between survivors and non-survivors among patients with "renal oligohydramnios" were oligohydramnios detection before 32 weeks GA, dysplasia detection on the second trimester ultrasound, and increase of serum creatinine from day 3 onwards. A higher resolution version of the Graphical abstract is available as Supplementary information.

Use of angiotensin II receptor blocker during pregnancy: A case report.

BACKGROUND: Drugs that affect the renin-angiotensin system, such as angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors are not typically recommended for pregnant women because of their potential fetal toxicity. CASE STUDY: A 32-year-old pregnant woman with nephrotic syndrome lasting more than 5 years became pregnant for the first time. She had been taking losartan tablets before and during pregnancy. Ultrasound at 24+2 weeks of pregnancy showed oligohydramnios, and the maximum vertical depth of amniotic fluid volume was 1.4 cm. Follow-up ultrasound examinations every 2 weeks showed persistent oligohydramnios [amniotic fluid volume: 1.1-3.4 cm, amniotic fluid index 1.9-6.9 cm]. B-ultrasound at 30+2 weeks showed slightly enhanced fetal renal cortex echo. The patient was treated at 32+2 weeks of pregnancy at our hospital. DIAGNOSES: Nephrotic syndrome and oligohydramnios. INTERVENTIONS: Losartan was discontinued and replaced by nifedipine controlled-release tablets to lower blood pressure. The amount of amniotic fluid gradually increased to normal levels within 8 days. The patient was discharged at 33+2 weeks of pregnancy for follow-up. At 34+4 weeks, blood pressure had increased to 177/113 mm Hg and the patient was re-hospitalized with nephrotic syndrome complicated by preeclampsia. Due to progression of severe preeclampsia, elective cesarean section was performed at 35+3 weeks. After delivery, losartan and nifedipine were prescribed to continue lowering blood pressure. The patient was discharged 4 days after surgery. OUTCOMES: Losartan use was terminated at 32+2 weeks of pregnancy. Amniotic fluid returned to normal after 8 days and the baby was delivered after 22 days. At last follow-up, the infant was 24 months old and healthy. CONCLUSION: Although ARBs are effective for treating hypertension, they should be replaced by other classes of anti-hypertensive drugs in pregnant women. Pregnant women who elect to continue using ARBs should be informed about risks, they should be carefully monitored during pregnancy, and their pregnancy should be allowed to proceed as long as clinically feasible in order to optimize maternal and infant outcomes.

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.

Etiology and management of early pregnancy renal anhydramnios: Is there a place for serial amnioinfusions?

Early pregnancy renal anhydramios (EPRA) comprises congenital renal disease that results in fetal anhydramnios by 22 weeks of gestation. It occurs in over 1 in 2000 pregnancies and affects 1500 families in the US annually. EPRA was historically considered universally fatal due to associated pulmonary hypoplasia and neonatal respiratory failure. There are several etiologies of fetal renal failure that result in EPRA including bilateral renal agenesis, cystic kidney disease, and lower urinary tract obstruction. Appropriate sonographic evaluation is required to arrive at the appropriate urogenital diagnosis and to identify additional anomalies that allude to a specific genetic diagnosis. Genetic evaluation variably includes karyotype, microarray, targeted gene testing, panels, or whole exome sequencing depending on presentation. Patients receiving a fetal diagnosis of EPRA should be offered management options of pregnancy termination or perinatal palliative care, with the option of serial amnioinfusion therapy offered on a research basis. Preliminary data from case reports demonstrate an association between serial amnioinfusion therapy and short-term postnatal survival of EPRA, with excellent respiratory function in the neonatal period. A multicenter trial, the renal anhydramnios fetal therapy (RAFT) trial, is underway. We sought to review the initial diagnosis ultrasound findings, genetic etiologies, and current management options for EPRA.

Amniotic fluid volume at presentation with early preterm prelabor rupture of membranes and association with severe neonatal respiratory morbidity.

OBJECTIVE: Amniotic fluid volume (AFV) plays an important role in early fetal lung development, and oligohydramnios in early pregnancy is associated with pulmonary hypoplasia. The aim of this study was to evaluate the association between AFV at the time of presentation with early preterm prelabor rupture of membranes (PPROM) and severe neonatal respiratory morbidity and other adverse pregnancy outcomes. METHODS: This was a retrospective study of all women with a singleton pregnancy, admitted to a single tertiary referral center between 2004 and 2014, for expectant management of PPROM at 20 + 0 to 28 + 6 weeks' gestation. The primary exposure was AFV at presentation, classified according to sonographic maximum vertical pocket (MVP) as: normal AFV (> 2 cm), oligohydramnios (≤ 2 cm and > 1 cm) or severe oligohydramnios (≤ 1 cm). The primary outcome was a composite variable of severe respiratory morbidity, defined as either of the following: (1) need for respiratory support in the form of mechanical ventilation using an endotracheal tube for ≥ 72 h and need for surfactant; or (2) bronchopulmonary dysplasia, defined as requirement for oxygen at postmenstrual age of 36 weeks or at the time of transfer to a Level-II facility. Adjusted odds ratios (aOR) and 95% CI for the primary and secondary outcomes were calculated for each AFV-at-presentation group (using normal AFV as the reference), adjusting for gestational age (GA) at PPROM, latency period, birth weight, mode of delivery and chorioamnionitis. RESULTS: In total, 580 women were included, of whom 304 (52.4%) had normal AFV, 161 (27.8%) had oligohydramnios and 115 (19.8%) had severe oligohydramnios at presentation. The rates of severe respiratory morbidity were 16.1%, 26.7% and 45.2%, respectively. Compared with normal AFV at presentation, oligohydramnios (aOR, 3.27; 95% CI, 1.84-5.84) and severe oligohydramnios (aOR, 4.11; 95% CI, 2.26-7.56) at presentation were associated independently with severe respiratory morbidity. Other variables that were associated independently with the primary outcome were GA at PPROM (aOR, 0.54; 95% CI, 0.43-0.69), latency period (aOR, 0.94; 95% CI, 0.91-0.98) and Cesarean delivery (aOR, 2.01; 95% CI, 1.21-3.32). CONCLUSIONS: In women with early PPROM, AFV at presentation, as assessed by the MVP on ultrasound examination, is associated independently with severe neonatal respiratory morbidity. This information may be taken into consideration when counseling women with early PPROM regarding neonatal outcome and management options. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal detection of isolated bilateral hyperechogenic kidneys: Etiologies and outcomes.

OBJECTIVES: To delineate the etiology and outcome of prenatally diagnosed isolated bilateral hyperechogenic kidneys (IBHK). STUDY DESIGN: Pregnancies with IBHK on prenatal ultrasound identified and followed by us between January 1, 2000 and January 1, 2015 were evaluated regarding the etiology and outcome by evaluation of family history, targeted AR-PKD and AD-PKD DNA analysis, and microarray analysis, according to renal size and amniotic fluid volume. RESULTS: Of the 52 identified cases, there were 34 cases with enlarged kidneys, 16 with normal size kidneys, and two with small kidneys. There were seven cases with AD-PKD, six inherited, and one with de novo causative variants in the PKD1 gene. Fifteen had AR-PKD, and microarray analysis showed two inherited findings: one with 17q12 deletion including the HNF1B/TCF2 gene inherited from asymptomatic mother and a duplication at 3p26.1 inherited from a healthy father. Of the remaining four cases, three cases had bilateral multicystic dysplastic kidneys, and one had unilateral renal agenesis. CONCLUSION: Microarray analysis and mutation analysis for PKD1 and PKHD1 have an important contribution to the diagnostic investigation of IBHK and to the management of affected and future pregnancies. Poor outcome was associated with large hyperechoic kidneys with oligohydramnios.

Urine biochemistry to predict long-term outcomes in fetuses with posterior urethral valves.

OBJECTIVE: Because the literature on the predictive value of fetal urinalysis is controversial in fetuses with lower urinary tract obstruction, we determined the best model of fetal urine biochemical markers correlated with long-term postnatal renal function based on glomerular filtration rate (GFR). METHOD: This retrospective study concerned 89 fetuses with lower urinary tract obstruction and their renal function after 10 years of age. We correlated fetal urine biochemical markers (total protein, ß2-microglobulin, sodium, chloride, glucose, calcium, and phosphorus) with GFR at 10 to 30 years of age in 89 patients with posterior urethral valves. We defined five stages of chronic kidney disease (CKD). RESULTS: Of the 89 patients, 18 (20%) are 20 years old or over. Postnatal renal function was good in 67.4% (GFR > 60 mL/min/1.73 m2 ) and poor in 17% (GFR < 30 mL/min/1.73 m2 ). All fetal urine markers differed between CKD stage 1 + 2 and CKD stage 4 + 5 (P < 0.001). ß2-microblobulin showed an 87% sensitivity for a 72% specificity. A combination of ß2-microglobulin and chloride gave the best results (93% sensitivity and 71% specificity) versus amniotic fluid volume (80% sensitivity and 73% specificity). CONCLUSION: Fetal urine biochemistry predicts long-term (10-30 years) postnatal renal function.

Diabetes Insipidus Presenting with Oligohydramnios and Polyuria During Pregnancy.

We report a case of subclinical central diabetes insipidus (DI), due to Rathke's cleft cysts, that was initially misdiagnosed as transient DI of pregnancy because it presented in the third trimester of pregnancy. A 37-year-old primigravida visited the Department of Obstetrics in the 30th week of gestation due to polyuria. She was admitted due to oligohydramnios; the amniotic fluid index was 3.24. A vasopressin challenge test was performed and her urine osmolality increased by >100% from baseline after the administration of desmopressin. Because central DI or transient DI of pregnancy was suspected, we prescribed her a desmopressin nasal spray. She gave birth to a relatively healthy baby at 37 weeks and 4 days of gestation. Several months after delivery, discontinuation of desmopressin resulted in recurrence of her polyuria. Magnetic resonance imaging of her brain revealed Rathke's cleft cysts, and finally central DI was diagnosed.

Lower urinary tract obstruction: fetal intervention based on prenatal staging.

The authors present an overview of lower urinary tract obstruction (LUTO) in the fetus with a particular focus on the insult to the developing renal system. Diagnostic criteria along with the challenges in estimating long-term prognosis are reviewed. A proposed prenatal LUTO disease severity classification to guide management decisions with fetal intervention to maintain or salvage in utero and neonatal pulmonary and renal function is also discussed. Stage I LUTO (mild form) is characterized by normal amniotic fluid index after 18 weeks, normal kidney echogenicity, no renal cortical cysts, no evidence of renal dysplasia, and favorable urinary biochemistries when sampled between 18 and 30 weeks; prenatal surveillance is recommended. Stage II LUTO is characterized by oligohydramnios/anhydramnios, hyperechogenic kidneys but absent renal cortical cysts or apparent signs of renal dysplasia and favorable fetal urinary biochemistry; fetal vesicoamniotic shunting (VAS) or fetal cystoscopy is indicated to prevent pulmonary hypoplasia and renal failure. Stage III LUTO is oligohydramnios/anhydramnios, hyperechogenic kidneys with cortical cysts and renal dysplasia and unfavorable fetal urinary biochemistry after serial evaluation; fetal vesicoamniotic shunt may prevent severe pulmonary hypoplasia but not renal failure. Stage IV is characterized by intrauterine fetal renal failure, defined by anhydramnios and ultrasound (US) findings suggestive of severe renal dysplasia, and is associated with death in 24 h of life or end-stage renal disease (ESRD) within the first week of life; fetal vesicoamniotic shunt and fetal cystoscopy are not indicated.

Severe antenatally diagnosed renal disorders: background, prognosis and practical approach.

Nowadays most renal disorders, especially urinary tract malformations and renal cystic disease, are diagnosed antenatally. In cases of severe bilateral disease, intrauterine renal dysfunction may lead to renal oligohydramnios (ROH), resulting in pulmonary hypoplasia which affects perinatal mortality and morbidity as well as the long-term outcome. However, some infants may only have mild pulmonary and renal disease, and advances in postnatal and dialysis treatment have resulted in improved short- and long-term outcome even in those infants with severe ROH. Here, we review the current state of knowledge and clinical experience of patients presenting antenatally with severe bilateral renal disorders and ROH. By addressing underlying mechanisms, intrauterine tools of diagnosis and treatment as well as published outcome data, we hope to improve antenatal counselling and postnatal care. KEY SUMMARY POINTS: 1. Nowadays most renal disorders are diagnosed antenatally, especially urinary tract malformations and renal cystic disease. 2. Severe kidney dysfunction may lead to renal oligohydramnios, which can cause pulmonary hypoplasia and is a risk factor of perinatal mortality and postnatal renal outcome. However, as considerable clinical heterogeneity is present, outcome predictions need to be treated with caution. 3. Advances in postnatal and dialysis treatment have resulted in improved short- and long-term outcomes even in infants with severe renal oligohydramnios. 4. A multidisciplinary approach with specialist input is required when counselling a family with an ROH-affected fetus as the decision-making process is very challenging.

Outcomes and management strategies in pregnancies with early onset oligohydramnios.

OBJECTIVE: To evaluate the outcomes and management options in pregnancies with early onset oligohydramnios. MATERIALS AND METHODS: The file datas of all pregnancies diagnosed as oligohydramnios or anhydramnios before 27 gestational weeks between January 2006 and September 2013 were evaluated retrospectively. The underlying pathology and associated anomalies, karyotype analysis, the outcome of the pregnancy (either termination or labour), and gestational week at the time of diagnosis were analyzed. RESULTS: A total of 54 pregnancies were evaluated; mean gestational week at the time of the diagnosis was 19.8 ± 4.6. Mean maternal age was 27.28 ± 6.03. Thirty-seven pregnancies were anhydramniotic, 13 fetuses had associated anomalies, five of them had multicyctic dysplastic kidney, five had bilateral renal agenesis, one had hypoplastic right heart syndrome, one had clubfoot, and one had ventricular septal defect and cleft palate. Karyotyping was normal regarding the fetuses with structural anomalies. Nineteen patients had premature preterm rupture of membranes and 39 patients had termination of pregnancy. CONCLUSION: The prognosis of early onset oligohydramnios is poor. Main determinant is gestational week at the time of the diagnosis.

Meckel-Gruber Syndrome with unilateral renal agenesis.

Meckel-Gruber Syndrome (MKS) is an autosomal recessive disorder, characterized by a combination of central nervous system malformation (occipital encephalocele), post-axial polydactyly, and enlarged polycystic kidney dysplasia. With a recurrence risk of 25% this lethal syndrome can be detected in early screening by ultrasound. However, to the authors' knowledge, association of MKS with unilateral renal agenesis was reported only once until now. Here, we describe a case of 26-year primigravida with 23 weeks pregnancy whose detailed sonographical examination of the fetus revealed large encephalocele through the posterior fontanelle microcephaly, anhydramnios, unilateral left enlarged polycystic kidney and right sided renal agenesis. The pregnancy was wilfully terminated on medical grounds. Risk for subsequent pregnancies was explained to the parents.

Renal oligo- and anhydramnios: cause, course and outcome--a single-center study.

PURPOSE: To evaluate the outcome of patients with renal oligohydramnios and explore the impact of patient variables on outcome and prognosis. METHODS: A retrospective single-center study was conducted analyzing 104 pregnancies complicated by oligohydramnios of renal origin from 2001 to 2011. Statistical analysis was performed to assess the influence of pre- and postnatal data on pregnancy outcome, morbidity and mortality. RESULTS: Prenatal renal diagnoses were as follows: hydronephrosis/megaureter: n = 21 (20.2 %), aberrance in renal form or location: n = 7 (6.7 %), cystic renal disease: n = 28 (26.9 %), renal dysplasia: n = 24 (23.1 %), renal agenesis: n = 42 (30.4 %), posterior urethral valves: n = 11 (10.6 %). Hydronephrosis/megaureter and late onset of oligohydramnios were prognostic factors for fetal survival, whereas renal agenesis and associated anomalies had a negative impact on pregnancy outcome. Prenatal interventions did not improve prognosis. CONCLUSIONS: Pregnancies complicated by renal oligohydramnios still have a poor outcome. Careful weighing of prognostic factors is necessary to decide about further therapeutic measures.

Are monoclonal antibodies a safe treatment for cancer during pregnancy?

Monoclonal antibodies (mAbs) are the cornerstone of the treatment of several types of tumors, but their use in pregnant women is not clearly defined. Here, we report and analyze all available data on mAb treatment in pregnant cancer patients. A literature search was performed from 2000 until January 2013 and all articles addressing safety of mAbs during pregnancy were reviewed. We found very few data on the use of bevacizumab in pregnant women. However, owing to its antiangiogenic effects and possible consequences on fetal development, it should be avoided during pregnancy. Trastuzumab administration has been associated with an elevated incidence of oligohydramnios and poor neonatal outcomes, particularly when prescribed after the first trimester for repeated infusions, and therefore it is not recommended. Rituximab does not seem to be teratogenic, but a transient prolonged neutropenia in the newborns was reported, without major infectious consequences in most cases. Few data are available about other mAbs, and hence their use during pregnancy remains discouraged.

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.

Neonatal ascites and oligohydramnios: the role of kidney.

Posterior urethral valve pathologies are the most frequent childhood obstructive uropathy reported, and we infer their presence on diagnosing foetal ascites and oligohydramnios. Early action is vital to determine the long-term development and the degree of impairment of renal function. We report a newborn male 34 weeks of gestation with a prenatal diagnosis of foetal ascites, fluid on the loose in renal fossa and oligohydramnios. Subsequent studies have shown the presence of posterior urethral valves with associated significant vesicoureteral reflux. There was no secondary renal damage. Intrauterine decompression of the urinary tract seems to have exerted a protective role against kidney damage. This finding supports the role of foetal decompression surgery in early and severely obstructive forms to improve the prognosis of renal function in the long term.

A case study of trastuzumab treatment for metastatic breast cancer in pregnancy: fetal risks and management of cerebral metastases.

Trastuzumab increases survival amongst women with human epidermal growth factor receptor (HER)-2 receptor positive metastatic breast cancer, but maternal and fetal risks are associated with advanced disease and its treatment in pregnancy. We present a case of a primigravid with HER-2 positive metastatic breast cancer who received trastuzumab throughout pregnancy. She presented with cerebral metastases, requiring surgical decompression and resection. Reversible oligohydramnios developed during pregnancy. Fetal safety data on trastuzumab in pregnancy is limited, but case reports suggest a recurring pattern of (mostly reversible) oligohydramnios.

Ultrasound evaluation of prognosis in fetuses with posterior urethral valves.

PURPOSE: The aim of this study was to evaluate the ability of prenatal ultrasound markers to predict postnatal renal prognosis in fetuses with posterior urethral valves. METHODS: Medical files on fetuses with prenatal diagnosis of posterior urethral valves from 2000 to 2006 were reviewed retrospectively. Data from prenatal follow-up included gestational age at diagnosis, ultrasound renal parenchyma evaluation, and presence and time of oligohydramnios onset. Prenatal parameters studied were correlated to postnatal renal function. RESULTS: Thirty-one male fetuses were included. Six pregnancies were terminated. Of the remaining 25 pregnancies that were continued, 4 children had abnormal creatine and 21 normal creatinine levels at follow-up. Presence and time of oligohydramnios onset did not differ between groups (P = .43). Ultrasound detected bilateral renal abnormalities in 3 fetuses (75%) with altered renal function, and 10 fetuses (55%) with normal creatinine, at follow-up. CONCLUSIONS: None of the ultrasound parameters evaluated were able to reliably predict postnatal renal function.