Fetal serum ss2-microglobulin and cystatin C in the prediction of post-natal renal function in bilateral hypoplasia and hyperechogenic enlarged kidneys

OBJECTIVES: To evaluate fetal serum ss2-microglobulin and cystatin C in the prediction of post-natal renal function in bilateral hypoplasia and hyperechogenic enlarged kidneys. Predicting post-natal renal function is crucial to the prenatal evaluation of fetal nephropathies. Prenatal ultrasound can identify terminal renal failure, but is not sensitive enough to identify infants whose post-natal renal function will be impaired. Fetal serum ss2-microglobulin and cystatin C are potential predictors of post-natal renal function. METHODS: Fifty-four prenatally diagnosed cases of bilateral nephropathy were retrospectively reviewed. Final diagnosis was established using histological or post-natal findings: renal hypoplasia (n = 7), cystic dysplasia (n = 9), autosomal dominant polycystic kidney disease (ADPKD; n = 8) or autosomal recessive polycystic kidney disease (ARPKD; n = 22) and transient sonographic abnormalities (n = 8). Fetal serum ss2-microglobulin and cystatin C were assayed respectively in 54 and 38 cases. The prognostic value of these markers was assessed in terms of the post-natal outcome. RESULTS: In bilateral kidney hypoplasia and cystic dysplasia, ss2-microglobulin and cystatin C were significantly (p < 0.0001 and p < 0.02 respectively) higher than in the normal control group. In hyperechogenic fetal kidneys (ARPKD, ADPKD and transient sonographic abnormalities), these markers were not different from controls. However, whereas normal values cannot exclude renal failure, abnormal values predict post-natal renal failure. CONCLUSIONS: In bilateral renal hypoplasia and dysplasia, fetal serum ss2-microglobulin and cystatin C are good markers for post-natal renal function. However, in bilateral renal hyperechogenic enlargement, abnormal values are associated with poor post-natal renal function, but normal values cannot preclude renal failure.     

Autosomal recessive polycystic kidney disease. Problems of prenatal diagnosis

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by different proportions of cystic dilated collecting ducts invariably associated with congenital hepatic fibrosis. Because of the nearly regular arrangement of nephrons and collecting ducts, disturbances have been postulated to act rather late on embryological grounds. Prenatal diagnoses seem to confirm this observation, as can be demonstrated in our cases and those reported in the literature. Increased echogenicity and renal enlargement are the main ultrasonographic signs of ARPKD; oligohydramnios is characteristic but not always present. Repeated sonographic measurements of the kidney length seem to be the most useful parameter. As differential diagnoses, autosomal dominant polycystic kidney disease as well as Meckel syndrome have to be taken into consideration. The prognosis of cases with oligohydramnios is usually poor. In genetic counselling, the possibility of prenatal diagnosis in the second trimester of pregnancy should be given with caution.     

Unusual sonographic features of ARPKD

The classic sonographic appearance of the kidneys in fetuses with autosomal recessive polycystic kidney disease (ARPKD) has been well described. We report a case of enlarged kidneys with pyramidal hyperechogenicity quite similar to medullary nephrocalcinosis found in a fetus at 34 weeks' gestation. At 39 weeks, a female neonate was delivered and died after 22 h due to pulmonary insufficiency secondary to severe oligohydramnios. On pathological analysis, the gross and microscopic findings were typical of ARPKD with diffuse dilatation of tubules throughout. The fetal renal lobulation was prominent and on section, the pyramids were delineated within each lobule, accounting for the clear image of the pyramids observed on sonography.     

Prenatal ultrasound,genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases

Purpose

To investigate the sonographic and clinical genotype–phenotype correlations in autosomal recessive polycystic kidney disease (ARPKD) and other cystic kidney diseases (CKD) in a large cohort of prenatally detected fetuses with hereditary CKD.

Methods

We retrospectively studied the clinical and diagnostic data of 398 patients referred with prenatal ultrasound findings suggestive of CKD between 1994 and 2010. Cases with confirmed hereditary CKD (n = 130) were analyzed as to their prenatal ultrasound findings, genotype, and possible predictors of clinical outcome.

Results

ARPKD was most common in our non-representative sample. Truncating PKHD1 mutations led to a significantly reduced neonatal prognosis, with two such mutations being invariably lethal. Sonographically visible kidney cysts occurred in only 3% of ARPKD cases. Renal abnormalities in Meckel syndrome (MKS) appeared earlier than in ADPKD (19.6 ± 3.7 vs. 29.8 ± 5.1 GW) or ARPKD (19.6 ± 3.7 vs. 30.2 ± 1.2 GW). Additional CNS malformations were not found in ARPKD, but were highly sensitive for MKS. Pulmonary hypoplasia, oligo/anhydramnios (OAH), and kidney enlargement were associated with a significantly worse neonatal prognosis.

Conclusion

Genotype, sonographic signs of OAH, enlarged kidney size, and pulmonary hypoplasia can be useful predictors of neonatal survival. We propose sonographic morphological criteria for ARPKD, ADPKD, MKS, and renal cyst and diabetes syndrome (RCAD). We further propose a clinical diagnostic algorithm for differentiating cystic kidney diseases.

     

Familial occurrence of isolated nonseptated nuchal cystic hygromata in midtrimester of pregnancy

OBJECTIVE: Nonseptated cystic hygromata of the fetal neck in midtrimester of pregnancy have been associated with chromosomal and structural malformations. Consequently, fetal karyotyping is frequently offered. We describe 18 families in which 18 pairs of siblings were affected by transient nonseptated cystic hygromata in utero. METHODS: Over a seven-year period, 18 families came to our attention, with a recurrent diagnosis of fetal nonseptated cystic hygromata in two subsequent pregnancies. Detailed anatomic surveys by transvaginal ultrasound were performed between 14 to 16 weeks' gestation on the basis of self-referral. Sonographic markers for fetal aneuploidy were specifically looked for. Nonseptated cystic hygroma was diagnosed when unilateral or bilateral cystic dilations in the anterolateral aspect of the fetal neck were present, as described by Bronshtein et al. (1989). All patients underwent amniocentesis, fetal echocardiography, and transabdominal follow-up ultrasound scan at 22 to 24 weeks' gestation. RESULTS: Thirty-six sibling fetuses with isolated nonseptated hygromata (unilateral n = 5; bilateral n = 31) were identified. Amniocentesis revealed normal karyotypes in all 36 fetuses, including 20 males and 16 females. Fetal echocardiograms and neonatal pediatric examinations were normal. Sonographic resolution of the cystic hygromata was noted in all cases at the 22 to 24 weeks' follow-up scan. One pregnancy, producing a female newborn, was conceived by a remarried mother. All others were reportedly conceived by the same partners. Probability calculations suggest that if our findings were explained by chance alone, a population base of 367,000 pregnancies would have to be scanned in order to find 18 pairs of siblings with nonseptated cystic hygromata. CONCLUSION: The familial occurrence and identical natural history of the cystic lesions in utero suggest the presence of an inheritable developmental syndrome affecting the lymphatic system in utero, but without long-term sequelae.     

Prenatal diagnosis of multiple acyl-CoA dehydrogenase deficiency: association with elevated alpha-fetoprotein and cystic renal changes.

We report the occurrence of multiple acyl-CoA dehydrogenase deficiency (MADD) in two consecutive pregnancies in a young, Caucasian, non-consanguineous couple. In the first pregnancy, the maternal serum alpha-fetoprotein was elevated. A sonogram showed growth delay, cystic renal disease, and oligohydramnios; the parents decided to terminate the pregnancy. Postmortem examination confirmed the cystic renal disease and showed hepatic steatosis, raising the suspicion of a metabolic disorder. The diagnosis of MADD was made by immunoblot studies on cultured fibroblasts. In the subsequent pregnancy, a sonogram at 15 weeks' gestation showed an early growth delay but normal kidneys. The maternal serum and amniotic fluid concentrations of alpha-fetoprotein were elevated, and the amniotic fluid acylcarnitine profile was consistent with MADD. In vitro metabolic studies on cultured amniocytes confirmed the diagnosis. A follow-up sonogram showed cystic renal changes. These cases provide additional information regarding the evolution of renal changes in affected fetuses and show a relationship with elevated alpha-fetoprotein, which may be useful in counseling the couple at risk. MADD should be considered in the differential diagnosis of elevated alpha-fetoprotein and cystic renal disease. Early growth delay may be an additional feature.     

Prenatal diagnosis of bilateral diaphragmatic hernia by fetal sonography

This report describes a case of prenatally diagnosed bilateral diaphragmatic hernia. At 22 weeks' gestation, ultrasound revealed a cystic structure behind the fetus's heart on the axial image at the level of the cardiac four-chamber view. This suggested a left-sided congenital diaphragmatic hernia with herniation of the stomach into the left hemithorax. However, the left-to-right midline shift of the heart was minimal, which is not typical of left-sided congenital diaphragmatic hernia. Throughout the 30th week of gestation, the right and left branches of the pulmonary artery were hypoplastic compared with the values in normal fetuses of the same gestational age. The presumptive diagnosis was bilateral congenital diaphragmatic hernia. A female newborn weighing 2900 g was delivered at 37 weeks' gestation, and she died at 7 h of age. An autopsy revealed large defects on both sides of the diaphragm. In conclusion, prenatal diagnosis of bilateral diaphragmatic hernia is possible with fetal sonography.     

Antenatally diagnosed congenital orbital teratoma in which rupture was associated with intrauterine fetal death

We report a case of a fetus with a congenital orbital teratoma (COT), in which rupture of the tumor was associated with an intrauterine fetal demise. An ultrasound scan at 27 weeks' revealed a solid and cystic, complex mass in the orbital region with extensive vascularization suggestive of an orbital cystic teratoma. Magnetic resonance imaging (MRI) supported this diagnosis and clarified tumor localization. At 32 weeks', the patient presented with fetal demise and rupture of the mass was noted. Fetal COTs, like sacrococcygeal teratomas, carry the risk of rupture. MRI in utero is useful for evaluating the extent of disease.     

Prognosis in Fetal Cystic Hygroma

Axillary and lateral cervical fetal cystic hygromas in a fetus with normal karyotype are described. Fetal death at 25 weeks' gestation occurred. A literature review revealed that for cystic hygroma 42% of infants are 45XO, 38% have a normal karyotype, and 18% have trisomies. Prognosis is grim if the karyotype is abnormal or if hydrops or bilateral pleural effusions are present. Survival rate progressively improves with normal karyotype (27%), unilateral pleural effusion (40%), atypical location (56%), and resolution of cystic hygroma (71%). No single feature signifies 100% survival. The overall survival rate for fetal cystic hygroma is 10%. Prognosis remains guarded regardless of all other factors until the fetus reaches 26 weeks' gestation, after which time a 67% chance of ultimate survival can be expected. Only 42% of documented survivors were completely normal at follow-up.     

Preimplantation genetic diagnosis for autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary renal cystic diseases, and is caused by mutations in the PKHD1 gene. Due to the poor prognosis, there is a strong demand for prenatal diagnosis. Preimplantation genetic diagnosis (PGD) represents an alternative because it avoids the physical and emotional trauma of a pregnancy termination in the case of an affected fetus. A standardized single-cell diagnostic procedure was developed, based on haplotype analysis, enabling PGD to be offered to couples at risk of transmitting ARPKD. Six linked markers within (D6S1714 and D6S243), or in close proximity to (D6S272, D6S436, KIAA0057, D6S1662) the PKHD1 gene were tested by multiplex nested-polymerase chain reaction (PCR), using a Qiagen multiplex PCR kit. PCR analyses were carried out on 50 single lymphocytes. The amplification rate was excellent (100%), with an allele drop-out (ADO) rate ranging from 0 to 8%. Five PGD cycles were performed and 23 embryos were biopsied and analysed using this test. Transferable embryos were obtained in 4 cycles, resulting in two pregnancies and the birth of a healthy boy. This standardized diagnostic procedure allowed the detection of recombination, contamination, and ADO events, providing high assay accuracy with wide applicability.     

Megacystis-microcolon-intestinal hypoperistalsis syndrome in two male siblings

Two male sibs with severe congenital megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) are presented. Both had enlarged bladder and hydronephrosis due to reduced bladder emptying, decreased bowel motility, and malrotation of the colon. Repeated careful ultrasound examination of the urinary tract in the second sib failed to show significant bladder enlargement prior to 25 weeks' gestation, which has been considered to be a reliable prenatal diagnostic sign for MMIHS. Slight bilateral enlargement of the renal pelves was noted at 21 weeks' gestation, and this may represent the earliest prenatally-detectable observation in this disease. Although more females than males with this condition have been reported, our cases provide support for an autosomal recessive mode of inheritance with a similar recurrence risk for both sexes.     

Renal disease in women with severe preeclampsia or gestational proteinuria

OBJECTIVE: To identify women with severe preeclampsia or severe gestational proteinuria at high risk of having underlying renal disease. METHODS: Between 1980 and 1999, 86 Japanese women who had severe hypertension, severe proteinuria, or both during pregnancy had postpartum needle biopsies of their kidneys. Diagnoses before biopsies were severe preeclampsia in 74 women and severe gestational proteinuria in 12. We compared clinical characteristics, such as antepartum hematuria and postpartum proteinuria, and maternal and neonatal outcomes with regard to presence of renal disease. RESULTS: Nineteen of 86 women (22.1%, 95% confidence interval [CI] 13.9%, 32. 3%) were diagnosed with underlying renal disease. Immunoglobulin A nephropathy was present in 12. Women with renal disease had a significantly earlier onset of proteinuria than those without (median 11 versus 32 weeks' gestation, P <.001). Eighteen of 19 women with renal disease had proteinuria, hypertension, or both before 30 weeks' gestation. Ten of 12 women with severe gestational proteinuria (83.3%, 95% CI 51.6%, 97.9%) had underlying renal disease. Eight of the 19 women had antepartum hematuria, and seven had elevated serum immunoglobulin A levels. In women with severe preeclampsia, onset before 30 weeks' gestation was the best predictor of underlying renal disease (odds ratio 34.1, 95% CI 3.8, 304.5). Women with renal disease had lower rates of severe hypertension (nine of 19 versus 59 of 67, P <.01) and small-for-gestational-age infants (four of 19 versus 34 of 67, P <.05) than those without renal disease. CONCLUSION: Women who had gestational proteinuria or preeclampsia before 30 weeks' gestation were more likely to have had underlying renal disease.     

Sonographic differentiation of a large fetal cystic hygroma from the amniotic band syndrome

An 18-year-old gravida 1, para 0 woman had an uncomplicated pregnancy until 22 weeks' gestation. Ultrasound examination revealed an abnormally shaped fetal head fixed against the placenta, minimal movement of the extremities, multiple bandlike projections traversing the uterine cavity, and bilateral pleural effusions. A diagnosis of amniotic band syndrome was suggested with subsequent termination of the pregnancy. Fetal examination revealed a large cystic hydroma, generalized edema with pericardial and pleural effusions, and Turner's syndrome. Illustrated is the difficulty in making the prenatal diagnosis of cystic hydroma and its confusion with amniotic band syndrome.     

The cyclophosphamide, hexamethylmelamine, 5 fluorouracil (CHF) regimen in the treatment of advanced and recurrent ovarian cancer

Fifty-one patients with advanced ovarian carcinoma were treated with a combination of cyclophosphamide, hexamethylmelamine, and 5-fluorouracil, CHF. Compared to the hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (Hexa-CAF) regimen, the omission of methotrexate in CHF did not detract from its antitumor activity and it was well tolerated with only mild to moderate toxicity. The CHF combination was as effective as Hexa-CAF and was particularly active in patients who had nonmeasurable/residual disease, classified as less than 2 cm in its greatest diameter at the initiation of chemotherapy. In future studies, CHF should be prospectively compared to other combination using Adriamycin and cis-platinum that with extended use can cause renal and cardiac damage in long-term survivors.     

The relationship between premature rupture of the membranes and the respiratory distress syndrome. An update and plan of management

The records of 340 infants of 36 weeks' gestational age or less were reviewed to study the relationship between premature rupture of the membranes (PRM) and the development of the respiratory distress syndrome (RDS). Twins and infants of diabetic mothers were excluded from the data analysis. PRM of 16 hours or more was associated with statistically significant reduction in the incidence of RDS in infants of 31 weeks' gestational age and older. The association between PRM in excess of 16 hours and survival, however, was only statistically significant for infants of 33 weeks' gestational age and older. The implications of these results and a proposed plan of management for premature infants with PRM are discussed.     

妊娠合并肾脏疾病28例的产科处理

目的探讨妊娠合并肾脏疾病的产科处理。方法对妊娠合并肾脏疾病28例病例的产科处理做回顾性分析。结果28例妊娠合并肾脏疾病中合并肾炎的发病率最高(20/28),妊娠并发症中妊娠期高血压疾病发生率最高(10/28)。24例肾功能代偿期孕妇均定期接受产科检查,除1例孕13周时行人工流产术外,其余23例均足月正常分娩,母儿预后良好;3例合并妊娠期高血压疾病子痫前期(重度)、肾功能不全(氮质血症期),除1例早产外,另2例剖宫产终止妊娠,母儿预后良好;另有1例孕期未进行产前检查,孕24周合并妊娠期高血压疾病子痫前期(重度),胎儿宫内发育迟缓,肾功能不全(尿毒症期),以剖宫产终止妊娠,胎儿死亡。结论妊娠结局与妊娠合并肾脏疾病中肾功能的分期和有无妊娠并发症密切相关;孕期检查和适时、适当的产科处理对于围生儿、孕妇的预后至关重要。     

Congenital chylothorax in neonatal thyrotoxicosis.

We report a patient with congenital chylothorax who also had neonatal thyrotoxicosis secondary to maternal Graves' disease. Fetal tachycardia with hydrops was detected at 28 weeks' gestational age. The fetus responded to antithyroid medication in utero but had persistent bilateral pleural effusion. At birth, he had respiratory distress due to massive pleural effusion. Cytologic studies of pleural fluid were consistent with chylothorax. To the best of our knowledge, the association of congenital chylothorax with fetal (neonatal) thyrotoxicosis, has not been reported previously.     

Fertility problems associated with cystic fibrosis

A case of a cystic fibrosis patient with two pregnancies that ended in deliveries at 30 and 29 weeks' gestation, respectively, is presented. The author suggests that the increased life expectancy of cystic fibrosis patients because of therapeutic advances will increase the need to examine the association and effects of fertility in individuals with this genetic disease.     

Fetal adrenal haemorrhage--two-dimensional and three-dimensional imaging

A case of prenatal adrenal haemorrhage first detected by 2-dimensional and 3-dimensional sonography at 27 weeks' gestation is reported. Ultrasound examination showed a large cystic mass (32 x 27 x 27 mm) in the right suprarenal region of the fetus. Two weeks later, the mass had slightly increased in size demonstrating hyperechoic areas within the cyst. Further serial ultrasound examinations revealed a progressive organisation of the cystic mass associated with a moderate reduction in size. The diagnosis of adrenal haemorrhage was confirmed by postnatal follow-up sonograms as the mass decreased in size from 28 x 21 x 21 mm on day 1 to 23 x 18 x 17 mm on day 42. Course and sonographic signs were typical for adrenal haemorrhage and the neonate was therefore managed without surgical exploration. The child is developing normally at 6 months of age.     

Recurrent fetal cystic hygroma with normal chromosomes: case report and review of the literature

Recurrence of fetal cystic hygroma in subsequent pregnancies is extremely rare. A review of the literature to date revealed only two other reports of recurrence with normal fetal karyotypes documented in at least two of the affected pregnancies. At 11 weeks' gestation, the fetus of a 19-year-old gravida 3 para 0 was discovered to have a large cystic hygroma. Subsequent evaluation during the second trimester revealed increasing size of the septated nuchal mass and ascites. A 46,XX fetal karyotype was noted in her two prior pregnancies, both of which had also been complicated by the development of cystic hygroma and nonimmune hydrops. Cystic hygroma, associated with a normal karyotype, can be inherited as an autosomal recessive trait.