Johannes Keunen

Successful Pregnancies on Nocturnal Home Hemodialysis

BACKGROUND AND OBJECTIVES Women of childbearing age on conventional hemodialysis (CHD) have decreased fertility when compared with the general population. Even in women who conceived, maternal morbidity and fetal mortality remained elevated. We hypothesized that nocturnal hemodialysis (NHD) (3 to 6 sessions per week, 6 to 8 h per treatment), by augmenting uremic clearance, leads to a more hospitable maternal environment and therefore superior outcomes in fertility and pregnancy compared with CHD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS This is a descriptive cohort study of all female patients achieving pregnancy and delivering a live infant while on NHD at the University Health Network, St. Michaels Hospital, and Humber River Regional Hospital from 2001 to 2006 in Toronto, Canada. Our primary objective was to describe maternal and fetal outcomes in addition to the changes in biochemical parameters after conception in our cohort. RESULTS Our cohort included five patients (age range, 31 to 37 yr) who had seven pregnancies while on NHD and delivered six live infants. All had previously been on CHD, but none conceived during that time. In all patients, the amount of hemodialysis was increased (from a weekly mean of 36 +/- 10 to 48 +/- 5 h; P < 0.01) after pregnancy was diagnosed. Mean predialysis blood urea and mean arterial BP were maintained within normal physiological parameters. The mean gestational age of the cohort was 36.2 +/- 3 wk and the mean birth weight was 2417.5 +/- 657 g. The maternal and fetal complications observed in the cohort included intrauterine growth restriction or small for gestational age (n = 2), preterm delivery (<32 wk) (n = 1), and shortened cervix threatened labor (n = 1). Anemia was accentuated during pregnancy, and intravenous iron and erythropoietin requirements were increased. To maintain normal physiological indices for plasma phosphate, an augmented dialysate phosphate supplementation regimen was required. CONCLUSIONS NHD may allow for improved fertility. Delivering a live infant at a mature gestational age is feasible for patients on NHD. Our cohort tended to have fewer maternal and fetal complications compared with historical controls. Hemoglobin and phosphate levels must be monitored with treatment adjusted accordingly.

Intensive Hemodialysis Associates with Improved Pregnancy Outcomes: A Canadian and United States Cohort Comparison

Pregnancy is rare in women with ESRD and when it occurs, it is often accompanied by significant maternal and fetal morbidity and even mortality. Preliminary data from the Toronto Nocturnal Hemodialysis Program suggested that increased clearance of uremic toxins by intensified hemodialysis improves pregnancy outcomes, but small numbers and the absence of a comparator group limited widespread applicability of these findings. We compared pregnancy outcomes from 22 pregnancies in the Toronto Pregnancy and Kidney Disease Clinic and Registry (2000-2013) with outcomes from 70 pregnancies in the American Registry for Pregnancy in Dialysis Patients (1990-2011). The primary outcome was the live birth rate and secondary outcomes included gestational age and birth weight. The live birth rate in the Canadian cohort (86.4%) was significantly higher than the rate in the American cohort (61.4%; P=0.03). Among patients with established ESRD, the median duration of pregnancy in the more intensively dialyzed Toronto cohort was 36 weeks (interquartile range, 32-37) compared with 27 weeks (interquartile range, 21-35) in the American cohort (P=0.002). Furthermore, a dose response between dialysis intensity and pregnancy outcomes emerged, with live birth rates of 48% in women dialyzed ≤20 hours per week and 85% in women dialyzed >36 hours per week (P=0.02), with a longer gestational age and greater infant birth weight for women dialyzed more intensively. Pregnancy complications were few and manageable. We conclude that pregnancy may be safe and feasible in women with ESRD receiving intensive hemodialysis.

The kidney in normal pregnancy and preeclampsia.

Complicating up to 8% of pregnancies, preeclampsia is, in fact, the most common glomerular disease worldwide. In this article, we review the effect of normal pregnancy on the kidney as well as the role of the kidney in preeclampsia. We discuss blood pressure in pregnancy and preeclampsia, followed by the physiology of hyperfiltration in normal pregnancy as well as the pathophysiology of hypofiltration and proteinuria in preeclampsia. Recent studies have suggested that the clinical syndrome of preeclampsia, which recovers rapidly after delivery of the placenta, is caused by impaired vascular endothelial growth factor signaling that disturbs the status of vascular dilatation as well as the symbiosis between the glomerular endothelium and the podocytes. Finally, we discuss the intriguing association between chronic kidney disease (CKD) and preeclampsia. We hypothesize that the imbalance between angiogenic and anti-angiogenic factors, which may be common to both preeclampsia and CKD, might explain why CKD predisposes pregnant women to develop preeclampsia.

Pregnancy in End Stage Renal Disease

The ovulatory menstrual cycle is known to be affected on multiple levels in women with advanced renal disease. Menstrual irregularities, sexual dysfunction, and infertility worsen in parallel with the renal disease. Pregnancy in women with ESRD on dialysis is therefore uncommon. Furthermore, when pregnancy does occur, it can prove hazardous to both mother and baby owing to a multitude of potential complications including accelerated hypertension and preeclampsia, poor fetal growth, anemia, and polyhydramnios. Data are emerging, however, to suggest that pregnancy while on intensified renal replacement regimens may result in better pregnancy outcomes, and emerging trends include the decreased rate of therapeutic abortions probably reflecting a change in counseling practices over time. Nevertheless, a pregnant woman on intensive dialysis requires meticulous follow‐up by a dedicated team including nephrology, obstetrics, and a full multidisciplinary staff. In this article, we will address fertility issues in young women with ESRD, review pregnancy outcomes in women on both hemodialysis and peritoneal dialysis, and provide suggestions for the management of the pregnant women on intensive hemodialysis.

Unfractionated heparin for second trimester placental insufficiency: a pilot randomized trial

Summary.  Objective: To conduct a pilot randomized controlled trial of unfractionated heparin (UFH) in women considered at high risk of placental insufficiency in the second trimester. Methods: Women with either false‐positive first trimester (pregnancy‐associated placental protein‐A [PAPP‐A] < 0.35 MoM) or second trimester (alpha‐fetoprotein [AFP] > 2.0 MoM, inhibin > 3.0 MoM, human chorionic gonadotropin > 4.0 MoM) serum screening tests or medical/obstetric risk factors were screened for placental insufficiency by sonographic evaluation of the placenta and uterine artery Doppler between 18 and 22 weeks. Thrombophilia screen‐negative women with two or three abnormal test categories were randomized by 23+6 weeks to self‐administration of subcutaneous unfractionated heparin (UFH) 7500 IU twice daily until birth or 34 weeks, or to standard care. Maternal anxiety and other maternal‐infant outcomes were determined. Results: Thirty‐two out of 41 eligible women consented, with 16 women randomized to UFH and 16 to standard care. There was no statistically significant difference identified between the two treatment groups (standard care vs. UFH) for the following: maternal anxiety score (mean [standard deviation]), 14.2 [± 1.6] vs. 14.0 [± 1.8]; birth weight (median [range]), 1795 [470–3295]g vs. 1860 [730–3050]g; perinatal death, 3 vs. 0; severe preeclampsia, 2 vs. 6; placental weight < 10th percentile, 7 vs. 4; or placental infarction, 4 vs. 3. Conclusion: Our study design identified women at high risk of adverse maternal‐infant outcomes attributable to placental insufficiency. Women with evidence of placental insufficiency were willing to undergo randomization and self‐administration of UFH without increased maternal anxiety.

Pregnancy Outcomes in Women With Spinal Cord Lesions

OBJECTIVE Women with spinal cord lesions present special challenges during pregnancy. We studied their pregnancy outcomes with regard to medical, obstetrical, and social concerns. METHODS We reviewed the records of pregnant women with spinal cord injury who attended our institution between 1999 and 2009. RESULTS Thirty-two women with a total of 37 pregnancies were identified. Most were nulliparous (65%) with either thoracic or lumbar spinal cord lesions due to neural tube defects (69%), trauma (19%), tumours (9%), or iatrogenic injury (3%). Most had undergone orthopedic surgery (63%) or neurosurgery (53%). The most common medical conditions were neurogenic bladder (53%), anemia (16%), autonomic hyperreflexia (9%), and elevated BMI > 30 (6%). Recurrent urinary tract infection occurred in 32%. Antibiotic suppression against bacteriuria was used in 35%. Antenatal hospitalization occurred in 46%, most often because of threatened preterm labour (19%). There were 33 live births and two stillbirths (6%). Preterm birth < 37 weeks occurred in 24%. Vaginal birth occurred in 33%. CONCLUSION Pregnant women with spinal cord lesions generally have successful pregnancy outcomes. However, their pregnancies are at significant risk for preterm birth, infection, and Caesarean section. Coordinated multidisciplinary care is recommended for optimal management of these pregnancies.

Congenital megalourethra: prenatal diagnosis and postnatal/autopsy findings in 10 cases

Congenital megalourethra is a rare urogenital malformation characterized by dilation and elongation of the penile urethra associated with absence or hypoplasia of the corpora spongiosa and cavernosa. Postnatal complications include voiding and erectile dysfunction as well as renal insufficiency and pulmonary hypoplasia. To date, only a few prenatally diagnosed cases have been reported. We report on 10 cases diagnosed prenatally and their postnatal/autopsy findings.

End-Stage Renal Disease and Pregnancy

Pregnancy in patients with ESRD is rare and remains especially challenging. Because endocrine abnormalities and sexual dysfunction decrease fertility, conception rates have been remarkably low in this patient population. Moreover, when pregnancy does occur, hypertension, preeclampsia, anemia, intrauterine growth restriction, preterm delivery, stillbirth, and other complications can decrease the rate of a successful outcome. However, recent experiences with intensive hemodialysis managed by a multidisciplinary team are encouraging with respect to better overall outcomes for mothers and infants. In this article, we discuss the main causes of decreased fertility in dialysis-dependent women, review outcomes and complications of pregnancy among dialysis patients with a special focus on recent intensive hemodialysis data, and summarize the current best strategy to manage pregnant women on dialysis.

Twin–twin transfusion syndrome: a frequently missed diagnosis with important consequences

To evaluate the incidence and consequences of ‘misdiagnosed’ cases of twin–twin transfusion syndrome (TTTS).

Incorporation of femur length leads to underestimation of fetal weight in asymmetric preterm growth restriction

To review the performance of a variety of biometry formulae for estimated fetal weight (EFW) in the management of severely growth restricted fetuses with abnormal umbilical artery Doppler at a single perinatal institution.