Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up.

OBJECTIVE--Determination of the long term incidence of uraemia, hypertension, and toxaemia in pregnancy associated with non-obstructive focal renal scarring after pyelonephritis in childhood 25-35 years earlier. DESIGN--27 Year follow up of patients with non-obstructive focal scarring identified from a retrospective review of intravenous urograms performed in childhood between 1951 and 1967. SETTING--Paediatric primary referral centre and urological clinic in tertiary referral centre. PATIENTS--30 Patients (mean age 33 (range 22-41] with non-obstructive focal renal scarring first detected between 1951 and 1967 and a history of febrile urinary tract infection. MAIN OUTCOME MEASURE--Hypertension and complications of renal damage. RESULTS--Three patients had developed end stage renal disease, seven had developed hypertension, two of 16 women had a history of toxaemia during pregnancy, and seven patients had undergone renal surgery during follow up. Of the 20 patients who had neither had renal surgery nor had end stage renal disease, all had a significantly lower glomerular filtration rate and renal plasma flow and higher diastolic blood pressure, mean arterial blood pressure, plasma renin activity, and serum beta 2 microglobulin concentration than 13 healthy age matched controls. Diastolic blood pressure and plasma renin activity were positively correlated (r = 0.50, p less than 0.05) and so were fractional sodium excretion and both systolic and diastolic blood pressures (r = 0.54, p less than 0.01, r = 0.51, p less than 0.01 respectively). The progress of renal damage was unrelated to the incidence of recurrent infections. CONCLUSIONS--Children with focal renal scarring due to pyelonephritis are at high risk of serious long term consequences. It is essential that they are given adequate attention and care during adolescence and pregnancy.     

Pregnancies in women with and without renal scarring after urinary infections in childhood.

OBJECTIVE--To compare the outcome of pregnancy in women with and without renal scarring after childhood urinary infections with that in unmatched controls. DESIGN--Retrospective study of pregnancies in women prospectively followed up from their first recognised urinary infection. SETTING--Tertiary referral centre in Gothenburg. SUBJECTS--111 Women attending an outpatient clinic for women with urinary infection during 1975-83, of whom 41 (65 pregnancies) were studied (19 women with renal scarring (32), 22 without scarring (33)), and 65 controls (65) randomly selected and matched for parity, age, smoking habits, and date of delivery. MAIN OUTCOME MEASURES--Urinary infections and complications in pregnancy. RESULTS--The incidence of bacteriuria during first pregnancies was significantly greater in women with (9, 47%) and without (6, 27%) renal scarring after childhood urinary infection than in controls (1, 2%) (p less than 0.001, 0.01 respectively). Symptomatic infections were seen only among women with a history of urinary infection: four women with renal scarring (three of whom had vesicoureteric reflux) developed pyelonephritis and three cystitis, and one woman without scarring developed pyelonephritis. Mean blood pressure was higher among women with severe renal scarring than controls (4/11 v 3/44; p less than 0.05) before and during pregnancy. There was no significant difference in the incidence of pre-eclampsia, operative delivery, prematurity, or birth weight. CONCLUSIONS--Women with a history of previous urinary infections had a high incidence of bacteriuria during pregnancy, and those with renal scarring and persistent reflux were prone to develop acute pyelonephritis. The risk of serious complications in pregnancy, however, was not increased in women with severe renal scarring, possibly owing to their continuous clinical supervision.     

Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk

Preeclampsia is a disorder of pregnancy diagnosed by gestational hypertension and proteinuria. Epidemiological evidence suggests that women who experience preeclampsia are at a greater risk of hypertension and heart disease later in life compared with women who had normal pregnancies. Our objective was to determine whether endothelial function is impaired in postpartum women with a history of preeclampsia in their first pregnancy. We measured forearm blood flow (FBF) by venous occlusion plethysmography in 50 healthy women: 16 with prior preeclampsia, 14 with a prior normotensive pregnancy, and 20 never pregnant controls. The postpartum women participated 6-12 mo after delivery. Heart rate (HR) and blood pressure (BP) were concurrently monitored on the contralateral arm. Hemodynamic variables were assessed at baseline and during a mental stress test known to elicit endothelium-dependent vasodilatation. We found that baseline FBF, HR, systolic BP, and diastolic BP did not significantly differ among the groups, whereas mean arterial pressure in the preeclamptic group was greater than that of the normal pregnancy group (P = 0.03). Stress-induced FBF (percent change over baseline) was reduced in the preeclamptic group compared with both the normal pregnancy and never pregnant groups (P = 0.06) and was significantly attenuated compared with women with prior normal pregnancies (91% vs. 147%, P = 0.006). These data demonstrate that women with a history of preeclampsia exhibit impaired endothelial function up to 1 yr postpartum. This observation may explain their increased risk for hypertension and cardiovascular disease.     

Kidney Disease and Pregnancy

The course of 41 pregnancies was studied in 25 patients with renal disease. Histological classification of the disease in each patient was made by renal biopsy. The analysis suggests that the course of pregnancy in women with coexistent renal disease correlates with the underlying renal lesion and probably with the glomerular filtration rate and blood pressure. In patients with heavy proteinuria there is increased oedema formation, making the nephrotic syndrome a frequent complication.     

Physical and activity changes associated with pregnancy in captive lowland gorillas (Gorilla gorilla gorilla)

The physical appearance and the behavior of five lowland gorilla females at two zoos were recorded before and during 14 pregnancies. Whereas only the quality of changes associated with pregnancy had been described previously, in this study the behavior of the females was recorded quantitatively and evaluated statistically. All females at Stuttgart showed distention of the abdomen three to four months before delivery and development of the breasts a few weeks before parturition. Milk was produced by the third month in one case, and in the sixth month or later in the others, sometimes after delivery. The female at Frankfurt stopped social play seven days after conception; the Stuttgart females, in general, stopped, in the first weeks of pregnancy. Social activity and locomotion decreased considerably within the first three months in all females and were significantly different between the pregnant and the nonpregnant state in all the Stuttgart females. In this study, as in others in the literature, behavioral changes were much more reliable signs of pregnancy than were physical changes. Thus the quantitative results confirm those obtained solely by qualitative observation.     

Self-monitoring of blood glucose in diabetic pregnancy.

Admission to hospital is usually recommended to achieve the best possible diabetic control during pregnancy. We have used blood glucose monitoring at home to find out if patients can achieve equally good control outside hospital. Twenty-five consecutive diabetic patients were studied, of whom 20 had taken insulin before pregnancy. Six of their 14 previous pregnancies had ended in perinatal death. The 25 women performed 4247 blood glucose measurements during their pregnancies. Overall the mean blood glucose concentration was 7.1 mmol/l (128 mg/100 ml); before meals the mean was 6.5 mmol/l (117 mg/100 ml). Mean concentrations were lower in the third trimester, but at no stage was control in hospital significantly better than at home. The mean hospital stay before delivery was 22 days, and all patients had live babies. Monitoring blood glucose concentrations at home produces greater understanding and motivation among patients, improves control early in pregnancy, and shortens time spent in hospital.     

A blood pressure cut-off level identified for renal failure, but not for macrovascular complications in type 2 diabetes: a 10-year observation study.

AIMS: Can a cut-off blood pressure level for major complications be identified? METHODS: A 10 years observation study in 385 type 2 diabetic patients. RESULTS: 158 patients were affected with myocardial infarction, stroke, renal failure or death, which occurred in 68, 55, 19 and 109 patients, respectively. No patient with a blood pressure below 140 mmHg and/or a diastolic blood pressure below 75 mmHg developed uraemia during the observation period. No such cut-off level was seen for myocardial infarction, stroke or death. CONCLUSIONS: This study shows that there seems to be a cut-off level for blood pressure for development of renal failure, while no level was found for cardio- or cerebrovascular disorders.     

Antenatal prophylaxis of Rh isoimmunization: 28-weeks'-gestation service program

Two (0.18%) of 1086 Rh-negative primigravidas or multigravidas treated similarly in all previous pregnancies, who were given a single injection of Rh immune globulin (300 μg) at 28 weeks'' gestation and subsequently were delivered of Rh-positive babies, had demonstrable Rh isoimmunization at the time of that injection and must be considered “logistic” failures of antenatal prophylaxis. The remaining 1084 (who were treated again after delivery) had no evidence of Rh isoimmunization at delivery and none of the 512 screened at 6 months after delivery appeared to be immunized. If the 28th-week injection had not been protective, one would have expected 14 of the 1084 to have been demonstrably Rh isoimmunized and evidence of Rh isoimmunization to have persisted in 6 of the 512 observed 6 months after delivery.Six of 719 Rh-negative multigravidas who had not received Rh immune globulin after previous pregnancies or had been treated only after delivery showed evidence of Rh isoimmunization despite a single injection of Rh immune globulin at 28 weeks in a subsequent pregnancy. In three of the six the cause was most likely “sensibilization” due to previous exposure to Rh-positive blood or an untreated Rh-positive pregnancy. in 3 of the remaining 716 (0.42%) there may have been true failure of antenatal Rh prophylaxis administered at the 28th week. One would have expected this figure to be 12 of 716 if antenatal Rh prophylaxis at 28 weeks'' gestation were totally unsuccessful.It is concluded that a single intramuscular injection of Rh immune globulin, 300 μg, is 88% effective in preventing Rh isoimmunization during pregnancy in Rh-negative primigravidas and in multigravidas treated antenatally in all previous pregnancies, and is 75% effective in preventing Rh isoimmunization in Rh-negative multigravidas untreated during previous pregnancies. The majority of failures are due to Rh isoimmunization during pregnancy prior to antenatal prophylaxis at 28 weeks.     

Bromocriptine treatment of female infertility: report of 13 pregnancies.

Thirteen pregnancies occurred in 12 women who were treated with bromocriptine for infertility. Pretreatment prolactin levels were recorded in 11 patients and were normal in three. Five patients had suspected pituitary tumours, and they received irradiation to prevent swelling of the pituitary and the consequent visual field defects caused by the pressure of the swollen gland on the optic nerve. Ten of the 13 pregnancies have come to term, and all the babies were normal. When a patient with a pituitary tumour developed a visual field defect in the 38th week of pregnancy labour was induced and the defect disappeared after delivery. No multiple pregnancies occurred and there were no major complications.     

Are the renal functional changes of human pregnancy caused by prostacyclin?

To investigate the hypothesis of others that the many characteristic physiological alterations of pregnancy are due to prostacyclin, the effects of this vasodilator prostaglandin on renal function and related variables were measured. Intravenous infusion of prostacyclin (7 ng/kg/min) for 90 minutes in seven healthy male volunteers resulting in a significant fall in diastolic blood pressure and increase in heart rate. No significant change occurred in renal plasma flow or glomerular filtration rate in response to the prostacyclin, but there were significant falls in uric acid clearance (16 +/- 1.3----10 +/- 1.5 ml/min/ 1.73m2) and in free water clearance (4.0 +/- 1.1-----0.5 +/- 0.4 ml/min) both of which rose rapidly to pre-infusion levels upon cessation of prostacyclin infusion. Plasma renin and aldosterone levels rose sharply during prostacyclin infusion, falling to pre-infusion levels rapidly afterwards. Although the haemodynamic alterations were similar, the renal functional effects of prostacyclin infusion were quite different from (and often opposite in direction to) those of normal pregnancy. This acute study therefore does not add support to the hypothesis suggested by others that these alterations in pregnancy are due to prostacyclin, and that deficiency of prostacyclin will lead to the changes of pregnancy-associated hypertension.     

Essential hypertension and pregnancy.

Approximately 1% of pregnancies are complicated by essential hypertension. During pregnancy the blood pressure often stabilizes or improves. In patients with sustained hypertension, prospective controlled studies have demonstrated enhanced fetal survival when the blood pressure was controlled with antihypertensive medication. Such medication must be chosen carefully to avoid fetal and mateerial toxicity, and diuretics and salt restriction during pregnancy should be avoided. Among patients with essential hypertension the problem accelerates late in pregnancy in 2% to 11%; the acceleration may be predicted by determination of maternal mean arterial pressures and intravascular volumes early in pregnancy. The treatment of accelerated hypertension is identical to that of severe pre-eclampsia. Fetal loss is considerable but can be lessened by careful fetal and maternal monitoring and early controlled delivery. The risks of pregnancy in most patients with essential hypertension are small, and essential hypertension is not a uniform contraindication to pregnancy.     

Prognosis in diabetic nephropathy.

OBJECTIVE--To assess the effect of long term antihypertensive treatment on prognosis in diabetic nephropathy. DESIGN--Prospective study of all insulin dependent diabetic patients aged under 50 with onset of diabetes before the age of 31 who developed diabetic nephropathy between 1974 and 1978 at Steno Memorial Hospital. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--Forty five patients (20 women) with a mean age of 30 (SD 7) years and a mean duration of diabetes of 18 (7) years at onset of persistent proteinuria were followed until death or for at least 10 years. INTERVENTIONS--Antihypertensive treatment was started a median of three (0-13) years after onset of nephropathy. Four patients (9%) received no treatment, and 9 (20%), 13 (29%), and 19 (42%) were treated with one, two, or three drugs, respectively. The median follow up was 12 (4-15) years. MAIN OUTCOME MEASURES--Arterial blood pressure and death. RESULTS--Mean blood pressure at start of antihypertensive treatment was 148/95 (15/50) mm Hg. Systolic blood pressure remained almost unchanged (slope -0.01 (95% confidence interval -0.39 to 0.37) mm Hg a year) while diastolic blood pressure decreased significantly (0.87 (0.65 to 1.10) mm Hg a year) during antihypertensive treatment. The cumulative death rate was 18% (8 to 32%) 10 years after onset of nephropathy, in contrast to previous reports of 50% to 77% 10 years after onset of nephropathy. As in previous studies, uraemia was the main cause of death (9 patients; 64%). CONCLUSIONS--The prognosis of diabetic nephropathy has improved during the past decade largely because of effective antihypertensive treatment.     

Ectopic pregnancy; early diagnosis,clinical errors and conservative operation

This report of eight years' experience with extrauterine pregnancy by a single gynecologist is an exposition of how the diagnosis was made or why it was missed. Of 26 diagnoses of ectopic pregnancy, five were false (20 per cent); and in three cases (10 per cent) the diagnosis was not made promptly-a total error of 30 per cent. Ectopic pregnancy will be discovered earlier if obstetric patients are always examined shortly after missing the first menstrual period.A palpable adnexal mass was present in 19 of 21 ectopic pregnancies (90 per cent). A mass was palpable in only one of five cases erroneously diagnosed as ectopic pregnancy (20 per cent).Decidual casts were passed by four patients, two of whom did not have ectopic pregnancy. If two gynecologists do not agree on the question of extrauterine pregnancy, a third opinion should be sought or culdoscopy employed. Enucleation of the conceptus and salvage of the oviduct is advocated.     

Clinical Trial of a Combination of Lynestrenol and Mestranol (Lyndiol) as an Oral Contraceptive Agent

Contraception with lynestrenol-mestranol (Lyndiol) was studied in 332 Mexican women during a period of two and one-half years. Side effects were minimal or transient. No pregnancies occurred in those who took the medication according to instructions. The women were followed with yearly pelvic examinations and Papanicolaou smears, serial endometrial biopsies and extensive studies of blood, liver and glandular function. Complete ophthalmological studies were done on 30 patients. No clinical or laboratory evidence of harmful effects could be demonstrated. Return to ovulation (using pregnanediol excretion and endometrial biopsies as parameters) occurred in all of 22 women studied in the first three post-treatment cycles. Eight posttreatment pregnancies and the resulting offspring were normal. The first post-treatment cycle, as with other oral contraceptives, was unpredictable and tended to be prolonged. It varied in length from 22 to 60 days.     

Pregnancy in patients presenting with hyperprolactinaemia.

Ninety-two pregnancies occurred in 76 hyperprolactinaemic patients treated with bromocriptine. Half conceived within three months of attempted conception. There was no evidence of an increased rate of spontaneous abortion, fetal abnormality, or multiple pregnancy; the three twin pregnancies occurred in women who were additionally treated with clomiphene and human chorionic gonadotrophin. Thirty-one patients had radiological evidence of a pituitary tumour; 14 with major radiograph changes in the pituitary fossa or serum prolactin concentrations greater than 100 ng/ml received pituitary irradiation before conception. None of the latter showed evidence of enlargement of the tumour during pregnancy. In contrast two of the four patients with similar tumours but who were not irradiated developed visual field defects, one with gross destruction of the pituitary fossa. Prophylactic treatment to limit subsequent tumour expansion during pregnancy in patients with prolactinomas is indicated, and pituitary irradiation before conception appears to be a safe and effective method to achieve this goal.     

Are the renal functional changes of human pregnancy caused by prostacyclin?

To investigate the hypothesis of others that the many characteristic physiological alterations of pregnancy are due to prostacyclin, the effects of this vasodilator prostaglandin on renal function and related variables were measured.

Intravenous infusion of prostacyclin (7 ng/kg/min) for 90 minutes in seven healthy male volunteers resulting in a significant fall in diastolic blood pressure and increase in heart rate. No significant change occurred in renal plasma flow or glomerular filtration rate in response to the prostacyclin, but there were significant falls in uric acid clearance (16 ± 1.3 → 10 ± 1.5 ml/min/ 1.73m²) and in free water clearance (4.0 ± 1.1 → −0.5 ± 0.4 ml/min) both of which rose rapidly to pre-infusion levels upon cessation of prostacyclin infusion. Plasma renin and aldosterone levels rose sharply during prostacyclin infusion, falling to pre-infusion levels rapidly afterwards.

Although the haemodynamic alterations were similar, the renal functional effects of prostacyclin infusion were quite different from (and often opposite in direction to) those of normal pregnancy. This acute study therefore does not add support to the hypothesis suggested by others that these alterations in pregnancy are due to prostacyclin, and that deficiency of prostacyclin will lead to the changes of pregnancy-associated hypertension.     

Neonatal effects of maternal administration of acebutolol.

Systolic blood pressure, heart rate, and blood glucose concentration were measured in the first three days of life in 10 infants born to mothers who had received acebutolol, a cardioselective beta-adrenergic-blocking agent, for hypertension in pregnancy and compared with values in 10 infants whose mothers had received methyldopa. The blood pressure was expressed as a percentage of the expected value. Blood pressure was significantly lower in the infants of the mothers given acebutolol (p less than 0.02, less than 0.01, and less than 0.01 respectively during the three days of observation). Heart rate was also lower, but the significance was only at the 0.05 level. Blood glucose was not significantly different between the two groups. These results suggest that care should be taken in prescribing beta-adrenergic-blocking drugs during pregnancy.     

Pregnancy and Delivery in Patients with Mastocytosis Treated at the Polish Center of the European Competence Network on Mastocytosis (ECNM)

Objective

To present current guidelines regarding treatment of mastocytosis in pregnancy on the example of observed patients.

Design

Case control national study.

Setting

Polish Center of the European Competence Network on Mastocytosis (ECNM).

Population or Sample

23 singleton spontaneous pregnancies in 17 women diagnosed with mastocytosis in years 1999–2014, before becoming pregnant.

Methods

Prospective analysis outcomes of pregnancies and deliveries.

Main Outcome Measures

Survey developed in cooperation with the Spanish Instituto de Estudios de Mastocitosis de Castilla-La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Red Espańola de Mastocitosis (REMA), Spain.

Results

All 23 pregnancies resulted from natural conception. Obstetrical complications recorded in the first trimester included spontaneous miscarriage (5 pregnancies). Four patients delivered preterm, including one delivery due to preeclampsia at 26 weeks which resulted with neonate death due to extreme prematurity. Five women delivered via cesarean: four due to obstetrical indications and one due to mastocytosis, during which no anesthesia related complications were recorded. Of patients delivering vaginally, two received extradural anesthesia, three required oxytocin infusion due to uterine hypotonia. No labor complications were recorded. In one woman with pregnancy-induced hypertension, early puerperium was complicated by the presence of persistent arterial hypertension. One neonate was born with the signs of cutaneous mastocytosis. Another neonate was diagnosed with Patau syndrome. Four women were treated for mastocytosis prior to conception and continued therapy after becoming pregnant. One patient was put on medications in the first trimester due to worsening of her symptoms. Pregnancy exerted only a slight effect on the intensity and frequency of mastocytosis-related symptoms observed. Worsening of the disease-related symptoms was documented in only four patients (23%). None of the patients showed the signs of anaphylaxis, either before becoming pregnant, or during pregnancy and puerperium.

Conclusions

There is no contraindication to pregnancy when mastocystosis-related pathologies are under appropriate medical control.     

Endothelial-derived nitric oxide and angiotensinogen: blood pressure and metabolism during mouse pregnancy

The regulation of blood pressure during pregnancy involves several biological pathways. Candidate genes implicated in hypertensive diseases during pregnancy include those of the renin-angiotensin system and nitric oxide synthase (NOS). We evaluated blood pressure and metabolic characteristics during pregnancy in mutant mice. These included mice with a null mutation in the endothelial NOS (eNOS) gene (Nos3(-/-)), four copies of the angiotensinogen gene (Agt(2/2)), and mutations in both genes [four copies of Agt and heterozygous deficient for eNOS (Agt(2/2)Nos3(+/-)), four copies of Agt and homozygous deficient for eNOS (Agt(2/2)Nos3(-/-))]. Blood pressure measurements of nulliparous females from mutant strains were compared with two common laboratory strains C57Bl6/J and SV129 throughout their first pregnancy. Serum and urine analysis for the evaluation of renal and liver physiology were measured in the prepregnant state and during the third trimester of pregnancy. Throughout pregnancy blood pressures in all mutant strains were higher compared with controls. Agt(2/2)Nos3(-/-) showed the highest blood pressures and C57Bl6/J the lowest. Control mice, but not mutant mice, showed a second trimester decline in blood pressure. No immediate differences were noted regarding behavioral characteristics, renal or liver function parameters. Mice deficient for eNOS, mice with overexpression of Agt, and mice with mutations in both genes demonstrated higher blood pressure throughout pregnancy. There was no evidence of renal dysfunction, liver dysfunction, or hemolysis among any of the strains studied. We conclude that Nos3 and Agt are important genes in the regulation of blood pressure during pregnancy.     

Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. Melbourne Diabetic Nephropathy Study Group.

OBJECTIVE--To compare the efficacy of angiotensin converting enzyme inhibition with calcium antagonism in diabetic patients with microalbuminuria. DESIGN--Randomised study of diabetic patients with microalbuminuria treated with perindopril or nifedipine for 12 months and monitored for one or three months after stopping treatment depending on whether they were hypertensive or normotensive. Patients were randomised separately according to whether they were hypertensive or normotensive. SETTING--Diabetic clinics in three university teaching hospitals. PATIENTS--50 diabetic patients with persistent microalbuminuria. In all, 43 completed the study: 30 were normotensive and 13 hypertensive; 19 had type I diabetes and 24 had type II diabetes. INTERVENTIONS--For 12 months 20 patients were given perindopril 2-8 mg daily and 23 were given nifedipine 20-80 mg daily. MAIN OUTCOME MEASURES--Albumin excretion rate, blood pressure, and glomerular filtration rate. RESULTS--Both perindopril and nifedipine significantly reduced mean blood pressure. During treatment there was no significant difference between those treated with perindopril and those treated with nifedipine with respect to albuminuria or mean blood pressure. Stopping treatment with both drugs was associated with a sustained increase in albuminuria and mean blood pressure. There was a significant correlation between mean blood pressure and albuminuria and also between the reduction in mean blood pressure and the decrease in albuminuria during treatment with both drugs. In hypertensive patients both drugs caused significant decreases in mean blood pressure and albuminuria. In normotensive patients there was no significant reduction in albuminuria with either regimen. CONCLUSIONS--In diabetic patients with microalbuminuria blood pressure seems to be an important determinant of urinary albumin excretion. Perindopril and nifedipine have similar effects on urinary albumin excretion, both preventing increases in albuminuria in normotensive patients and decreasing albuminuria in hypertensive patients.