Successful management with C1-inhibitor concentrate of hereditary angioedema attacks during two successive pregnancies: a case report

Backgroud Hereditary angioedema (HAE) is a rare genetic disorder caused by a deficiency of the plasma protein C1 inhibitor (C1-INH). HAE is characterised by the onset of angioedema, which may develop in one or several organs, and may last from a few hours to several days. Oedema of the upper airway can be life-threatening. As a result of hormonal changes, some women experience more frequent angioedema attacks during pregnancy. During pregnancy, antifibrinolytic agents should only be used with caution, and attenuated androgens are contraindicated; therefore, replacement therapy with C1-INH concentrate represents one of few therapeutic options, but it is not widely documented. Case study We report the first case study of the successful management with regular infusions of C1-INH concentrate, of two successive pregnancies in a patient with HAE. During the second half of the first pregnancy, C1-INH was administered on demand at home. For the second pregnancy, on demand treatment was intensified to prophylactic therapy, with once or twice weekly infusions from the middle of the second trimester in order to efficiently control the frequent attacks. Conclusions This report illustrates that HAE can be successfully managed during pregnancy with C1-INH infusions at home. Since the number of crises may vary between pregnancies, the treatment regimen must be adapted to the patient’s need.     

Preeclampsia recurrence and prevention

Women with a previous pregnancy complicated by preeclampsia have an increased risk for recurrence in subsequent pregnancies. For severe preeclamptic women in an initial pregnancy, recurrence rates for any type of preeclampsia are very high, approaching 50% in some studies. Significant maternal and fetal complications are more common in recurrent preeclampsia compared with an initial episode. For women who have experienced a pregnancy complicated by preeclampsia, a systematic evaluation for underlying risk factors may identify a specific pathway suitable for a specific intervention. Although some progress has been made in developing potential therapeutic options to prevent preeclampsia recurrence, there is a great need for better data to determine who will benefit most from any specific therapy.     

Recidiva de melanoma en gestación

The incidence of malignant melanoma during pregnancy has been estimated to be 0.1 to 2.8 per 1,000 pregnancies. In women with a history of melanoma, pregnancy does not seem to increase the risk of recurrence or to negatively influence survival. However, survival is approximately 6 months shorter in women with recurrent disease and those requiring treatment during pregnancy. Malignant melanoma is the most common type of cancer to metastasize to the placenta and fetus. We report the case of a pregnant woman with a history of melanoma who showed cerebral recurrence and died 21 days post-partum, without placental or fetal metastases.     

A case of recurrent hyperreactio luteinalis

Hyperreactio luteinalis (HL) in normal pregnancy has been reported previously. However, only a few cases of HL recurrence have been reported. The present report describes HL in a normal singleton pregnancy presenting with an acute abdomen requiring surgical intervention. In a subsequent normal singleton pregnancy, HL recurred and was treated conservatively.     

Sodium excretion in normal and hypertensive pregnancy: a prospective study

One hundred fifty-eight intravenous saline solution infusions (3 mmol Na per kilogram body weight) were performed in (1) normal primigravid women during the second and third trimesters and post partum, after 1 week of either a high, low, or ad libitum salt intake; (2) normotensive primigravid women during midpregnancy who later developed pregnancy-induced hypertension, and (3) seven proteinuric and seven nonproteinuric primigravid women with ad libitum salt intake who had established pregnancy-induced hypertension. Sodium excretion did not differ significantly between pregnancy and after pregnancy despite marked differences in plasma renin activity, aldosterone concentration, volume, and glomerular filtration rate. Sodium excretion after saline solution loading varied according to prestudy sodium intake and was reduced between the second and third trimesters, independent of dietary salt intake. Those destined to develop pregnancy-induced hypertension had sodium excretion similar to that of continuously normotensive subjects during the second trimester, but those with established proteinuric pregnancy-induced hypertension had the lowest plasma volume, plasma aldosterone concentration, and plasma renin activity and retained sodium to the same degree as salt-deplete women with normotension. These results demonstrate that the balance of sodium regulatory factors is similar between pregnancy and post partum, that prestudy salt intake and stage of gestation can alter the natriuretic response to saline solution loading, and that normal pregnant women retain more administered sodium in late pregnancy than in midpregnancy despite further increases in plasma volume and no alterations to blood pressure or glomerular filtration rate. Those with established proteinuric pregnancy-induced hypertension retain sodium avidly without stimulation of plasma renin activity or plasma aldosterone concentration, findings not apparent during midpregnancy in those who later developed this disorder.     

Plasma cholinesterase activity in normal pregnance and in eclamptogenic toxemias

Plasma cholinesterase (ChE) activity during pregnancy has been found by several investigators^1–3 to be decreased compared to that in the nonpregnant state. Herschburg⁴ and Tourtellotte and Odell² have reported that plasma ChE activity in toxemia of pregnancy is even lower than in normal pregnancy.The mechanism by which this reduction of plasma ChE activity is produced in pregnancy has not been elucidated. Tourtellotte and Odell did not detect any enzyme inhibitors in maternal plasma or activators in plasma from nonpregnant individuals to account for the decrease. They suggested the possibilities that it might be related to the hemodilution which normally occurs in pregnancy or that it might represent an expression of altered hepatic function in pregnancy. Studies of the relationship of estrogen to plasma ChE activity in rats by Sawyer and Everett^{5, 6} showed that the enzyme activity varied with the presence or absence of estrogen, falling after castration of female rats to the level found in males. Conversely, the administration of estrogen to castrate male rats was followed by a significant increase in plasma ChE activity. Barnes and Epperson³ were unable to demonstrate such an estrogen-enzyme relationship in human beings.The present report includes the study of plasma ChE activity of normal nonpregnant females, of normal pregnant women at various periods of gestation and at 6 days and 6 weeks post partum, of women with eclampsia and severe pre-eclampsia, and of the term fetus. The possibility that the variations in plasma ChE activity in pregnancy primarily reflect changes in plasma volume has been investigated.     

On the influence of orciprenaline on uterine motility and on plasma levels of estradiol-17β in pregnant and parturient sheep

Orciprenaline infusions in laboring ewes suppressed uterine activity. A complete inhibition of uterine activity could only be obtained in the empty uterine horn of laboring ewes. During late pregnancy a complete inhibition of the pregnant horn could be established with orciprenaline doses much lower than those necessary during parturition. In all treated ewes, aberrant patterns of plasma estradiol-17β levels were observed: very high maternal estradiol-17β levels were detected after treatment with orciprenaline. It is suggested that orciprenaline influences fetal adrenocortical functioning.     

Recurrent gestational diabetes: risk factors, diagnosis, management, and implications

Gestational diabetes mellitus (GDM) should be regarded as a sentinel event in a woman's life that presents challenges and disease prevention opportunities to all providers of health care for women of reproductive age. Prediabetic risk factors are rising in prevalence and include dietary and lifestyle habits, which when superimposed on genetic predisposition contribute to the rising prevalence of type 2 diabetes and GDM. There is growing evidence that treatment of GDM matters, with a continuum of adverse pregnancy outcome risks proportional to degrees of maternal glucose intolerance. GDM in an index pregnancy increases the risk of recurrent GDM in subsequent pregnancies, and recurrence rates of up to 70% have been reported. GDM recurrence rates are influenced by maternal health characteristics and past pregnancy history. The risk of later metabolic syndrome and type 2 diabetes is increased in women with a history of GDM and women should be screened for postpartum glucose intolerance. Opportunities to prevent recurrent GDM and later type 2 diabetes require attention to risk factors and plasma glucose status with identification of impaired fasting glucose or impaired glucose tolerance.     

Low plasma volume following pregnancy complicated by pre-eclampsia predisposes for hypertensive disease in a next pregnancy

Objective A large number of women with a history of pre-eclampsia/HELLP have a low plasma volume at least six months postpartum. The objective of this study was to determine whether a low plasma volume in formerly pre-eclamptic women and HELLP patients is associated with an increased risk for recurrent hypertensive complications in a next pregnancy.
Design Prospective observational study.
Setting Tertiary obstetric centre.
Sample Formerly pre-eclamptic women and controls.
Methods In 316 women with a history of pre-eclampsia and/or HELLP, we measured, plasma volume along with haemodynamic, metabolic and haemostatic variables at least six months postpartum. A group of 22 healthy parous controls was used as a reference. After standardising plasma volume for body mass index, women were subdivided into normotensive and normal plasma volume (   n = 199  ), normotensive and low plasma volume (   n = 76  ) and hypertensive (   n = 41  ) subgroups, which were compared for demography, clinical parameters and course of a next pregnancy.
Main outcome measures Recurrent hypertensive disease of pregnancy.
Results Relative to the normal plasma volume subgroup, normotensive women in the low plasma volume subgroup have a higher body mass index, a lower total vascular compliance and a shorter estimated systemic circulation time. They have a higher HOMA index and higher fasting triglyceride levels. In normotensive and hypertensive former patients alike, low plasma volume is associated with a higher recurrence of hypertensive complications in a next pregnancy compared with normotensive women with normal plasma volume.
Conclusion Low plasma volume in normotensive women with a history of pre-eclampsia and/or HELLP is associated with overweight, reduced vascular compliance and insulin resistance and a predisposition for recurrent pre-eclampsia and HELLP syndrome in a next pregnancy.     

Discussion

The interrelationship of sodium intake and blood pressure regulation during pregnancy is not clear. The effects of dietary sodium loading and restriction on plasma levels of catecholamines, mean arterial pressure, and vascular response to two pressor agents, Levophed and angiotensin II, were investigated in 49 chronically prepared primigravid rabbits. Sodium loading increased mean arterial pressure (p < 0.005), but did not alter the response to either pressor agent. Sodium restriction did not alter mean arterial pressure, but did increase plasma norepinephrine (p < 0.05) and epinephrine (p < 0.02). Negative correlations between plasma levels of norepinephrine and vascular response to infusions of both pressor agents were observed during sodium restriction, ?0.61 (p < 0.05) for angiotensin II, and ?0.74 (p < 0.05) for norepinephrine. A similar correlation of ?0.81 (p < 0.05) was observed for angiotensin II in control animals. Norepinephrine appears to play a significant role in blood pressure maintenance and vascular response in pregnancy. This role is enhanced during sodium restriction.     

The metabolism of androstenedione in human pregnancy: the use of constant infusion of unlabeled steroid to assess its metabolic clearance rate, its production rate, and its conversion into androgens and estrogens

Using constant infusion of unlabeled steroid, we have studied the metabolic clearance rate (MCR), half-life (T 1/2), and conversion ratio of androstenedione (A) into androgens and estrogens throughout human pregnancy. In nonpregnant women, results obtained by infusion of unlabeled A were identical to those obtained by the infusion of either labeled steroid or a mixture of labeled and unlabeled steroid. A twofold increase in the infusion rate did not change any of these results, indicating that enzyme availability was not a limiting step. When compared to the nonpregnant state, pregnancy was associated with a twofold rise in plasma A production rate (PR) (p less than 0.05) but with minimal changes in its MCR or its T 1/2, thus leading to a twofold increase in the plasma concentration of A (p less than 0.05). The conversion of A into testosterone (T) rose twofold at term pregnancy (p less than 0.05), whereas that of A into estrone (E1) rose fivefold (p less than 0.01) and that of A into estradiol (E2) rose 16 fold (p less than 0.001). It is concluded that constant infusions of unlabeled A can be used successfully to study the kinetics of A when one is reluctant to infuse isotopic steroid.     

5-Hydroxytryptamine (serotonin), copper and ceruloplasmin plasma concentrations in spontaneous abortion.

Ceruloplasmin, the blue copper-protein of the blood plasma, is believed by some workers to be involved in the metabolic management of 5-hydroxytryptamine (serotonin) during pregnancy. 5-Hydroxytryptamine is abortifacient in experimental animals. By some authors, a role has been suggested for it in human abortion. The plasma concentrations of 5-hydroxytryptamine, copper and ceruloplasmin were measured in non-pregnant women, in normal early pregnancy and in cases of spontaneous abortion. Compared with normal early pregnancy, cases of inevitable abortion show lower values for both plasma copper and ceruloplasmin and higher values for plasma 5-hydroxytryptamine. The possible implications of these findings are discussed in view of the alterations in ceruloplasmin values in pregnancy and in the light of what is known of the pharmacology and metabolism of 5-hydroxytryptamine. It it believed that these alterations in plasma copper, ceruloplasmin and 5-hydroxytryptamine in cases of inevitable abortion are the effect, rather than the cause, of abortion.     

Treatment of recurrent eczema herpeticum in pregnancy with acyclovir

Background: Eczema herpeticum is an uncommon manifestation of an infection with herpes simplex virus (HSV). The disease is primarily seen in patients with histories of atopic eczema. Eczema herpeticum may be a life-threatening illness, but the mortality is felt to be <10% with modern antiviral and antibacterial agents. The use of acyclovir for other viral infections secondary to herpesvirus in pregnancy has been well documented. The authors now present a case report of eczema herpeticum treated with acyclovir during pregnancy.Case: A patient with a history of eczema herpeticum presented in pregnancy with a recurrence. She was successfully treated with intravenous (IV) acyclovir with good maternal and fetal outcome.Conclusion: Acyclovir may be utilized in pregnancy for several manifestations of HSV including eczema herpeticum.     

Vulvar carcinoma presenting during pregnancy,associated with recurrent bone marrow hypoplasia: a case report and literature review

BACKGROUND: Carcinoma of the vulva has predominantly been a disease of the elderly. Although occasionally it occurs in women under the age of 40 years, carcinoma of the vulva has been rarely diagnosed in pregnancy. Bone marrow hypoplasia can occur as a transient, pregnancy-related event; however, the recurrence of this pathology in future pregnancies is quite rare in the literature. CASE: A 29-year-old woman in her second pregnancy that was complicated by bone marrow hypoplasia had developed a squamous vulvar carcinoma. Each of these two conditions are quite rare in pregnancy, they may have occurred by chance, but there is a hypothetical possibility that bone marrow hypoplasia is an autoimmune disorder, with vulvar carcinoma occurring as a further complication in this immunoimpaired individual. CONCLUSION: This case also emphasizes the need to consider malignancy as a differential diagnosis in vulvar ulcers occurring in young women.     

Paclitaxel and Platinum Chemotherapy for Ovarian Carcinoma during Pregnancy

BACKGROUND: Ovarian cancer diagnosed during pregnancy is uncommon. Paclitaxel-based chemotherapy during pregnancy has not been reported previously. CASE: A woman with ascites and an adnexal mass diagnosed during pregnancy at 27 weeks gestational age underwent a laparotomy with cytoreductive surgery and was diagnosed with stage IIIC papillary serous ovarian adenocarcinoma. She was treated with three cycles of paclitaxel and cisplatin during pregnancy. At 37 weeks, she underwent a cesarean section, abdominal hysterectomy, and cytoreduction. Three additional cycles of chemotherapy were given. She developed a recurrence within 6 weeks of completing chemotherapy. She received several cycles of chemotherapy, but died of recurrent cancer 29 months after diagnosis. The infant has normal growth and development at 30 months of age. CONCLUSION: This is the first reported case of paclitaxel use during pregnancy.     

Preeclampsia--abnormal uterine artery Doppler is related to recurrence of symptoms during the next pregnancy

BACKGROUND: Impaired trophoblast invasion is suggested as the main cause of reduced placental perfusion, which results in fetal growth restriction and preeclampsia. Immunological response against the invading tissue has been given as the explanation. Preeclampsia frequently recurs during the next pregnancy. Doppler ultrasound can predict increased vascular impedance in the uteroplacental circulation. Whether signs of increased vascular resistance in pregnancies complicated by preeclampsia are predictive of recurrence during the next pregnancy is unknown. METHODS AND MATERIAL: Uterine artery Doppler was performed in 570 pregnant women with preeclampsia. Of these, 139 became pregnant again. The uterine artery Doppler results during the first pregnancy were related to symptoms of preeclampsia in the succeeding pregnancy. RESULTS: Preeclampsia developed again in 43 of the 139 women. Pregnancies with signs of increased uterine artery vascular impedance during the first pregnancy were 3.4 times more likely to develop preeclampsia again (CI 1.58-7.6). Similar results for a small for gestational age newborn were 9.7 (CI 1.1-90). CONCLUSION: Increased uterine artery vascular impedance in pregnancies complicated by preeclampsia increases the likelihood of recurrence and growth restriction during the next pregnancy. The Doppler information gathered during the first pregnancy might thus select cases for special surveillance and possibly prophylactic anti-platelet treatment in the next pregnancy.     

Materno-fetal platelet allo-immunization revealed by in utero intracerebral fetal hemorrhage: proposed management for the next pregnancy

Materno-fetal platelet allo-immunization causes fetal or neonatal thrombocytopenia and sometimes severe intracerebral bleeding. The HPA-1s antigen is most generally implicated. This accident can occur during the first pregnancy with a major risk of severe recurrence during the next pregnancy. These women require specific care in a specialized center although no consensus has been reached on management of second pregnancies. Proposed treatments include immunoglobulins and/or corticosteroids, fetal blood puncture and unique or iterative platelet transfusions.     

The effect of estrogen antagonism on progesterone production in early pregnancy in the baboon (Papio cynocephalus)

These studies were designed to investigate the role of estrogen on progesterone production in early pregnancy in the baboon, when the contribution of the corpus luteum and placenta has not been established. Oral administration of the estrogen antagonist MER-25 at two dosage levels (15 and 30 mg/kg/day) to the pregnant baboon from days 35 to 55 after conception results in a decline in peripheral plasma levels of progesterone within a few days and persists for at least 20 days after the termination of treatment with no effect on plasma estradiol levels. The same study was done with the use of a different estrogen antagonist, trioxifene mesylate (5 mg/kg/day), and there was no effect on plasma progesterone, although a transient depression in plasma estradiol was evident. These actions may be due to an inherent estrogenicity of trioxifene. In preliminary studies an effect of these estrogen antagonists on placental size and morphology has been observed. Estrogen deprivation in early pregnancy of the baboon results in a depression in plasma progesterone and indicates a placental requirement for estrogen in progesterone product at this stage of pregnancy.     

Pulmonary endometriosis in pregnancy

A case of parenchymal pulmonary endometriosis, a very rare gynecologic problem, is presented. Hormonal suppressive therapy was accomplished by pregnancy. This patient has remained free of symptoms as she has been breast-feeding and amenorrheic. Long-term follow-up is essential because of the high recurrence rate.     

A prospective study of plasma angiotensin-converting enzyme in normotensive primigravidae and their infants

Plasma angiotensin-converting enzyme (ACE) has been measured prospectively throughout pregnancy, at delivery and in the puerperium in 18 normotensive primigravidae and their infants. Plasma ACE was consistently lower during pregnancy than in comparable, non-pregnant controls, but rose progressively from about 30 weeks to term. At vaginal delivery maternal and fetal ACE levels did not differ significantly. There was a steady increase in maternal ACE activity up to 6 weeks post partum, when the levels were not significantly different from non-pregnant controls. No correlation could be found between plasma ACE and plasma renin activity or concentration, or plasma AII. Plasma aldosterone increased in parallel with ACE during the last ten weeks of pregnancy.