The answer is 2. According to the SEGO (Spanish Society of Gynecology and Obstetrics) in its 2005 protocol "Gestational trophoblastic disease", the risk of malignization, i.e. of developing a gestational trophoblastic neoplasm, ranges from 5 to 20% depending on whether it is a partial mole or a complete mole, respectively. According to this protocol: "Patients will be monitored weekly with hcg dosage until it becomes undetectable, for three consecutive times. After that the monitoring will be monthly, for six months and then every two months for another six months. Based on the available data, a follow-up of three to six months is recommended for partial mole and 12 months for complete mole." Therefore, subsequent controls are strictly necessary.The risk of a new molar gestation, although increased compared to the normal population, is not 50%.

[HIDDEN] According to the SEGO (Spanish Society of Gynecology and Obstetrics) in its 2005 protocol "Gestational trophoblastic disease", the risk of malignization, i.e. of developing a gestational trophoblastic neoplasm, ranges from 5 to 20% depending on whether it is a partial mole or a complete mole, respectively. According to this protocol: "Patients will be monitored weekly with hcg dosage until it becomes undetectable, for three consecutive times. After that the monitoring will be monthly, for six months and then every two months for another six months. Based on the available data, a follow-up of three to six months is recommended for partial mole and 12 months for complete mole." Therefore, subsequent controls are strictly necessary.The risk of a new molar gestation, although increased compared to the normal population, is not 50%.

A 24-year-old woman, primigestation, suffers a spontaneous abortion at 7 weeks gestation. The anatomopathological study of the abortive remains indicates molar disease. We should inform you that:

The risk of a new molar gestation in a future pregnancy is 50%.

You should not become pregnant until periodic controls and have spent one year with negative BHCG levels.

Subsequent controls are not necessary if the evacuation of the trophoblastic tissue was complete.

It is necessary to perform periodic controls since 40% of the cases will develop a gestational trophoblastic neoplasia.

[Gestational trophoblastic tumors and recent clinical information].

Recent clinical advances in the field of gestational trophoblastic diseases are described. WHO modified its risk factor scoring system. This change was proposed to combine both the basic FIGO anatomic staging with the modified WHO risk factor scoring system. Patients who score as low-risk are treated with single agent chemotherapy, such as methotrexate (MTX), and patients refractory to MTX are treated with a combination chemotherapy, EMA/CO. Patients who score as high-risk are treated with EMA/CO, and patients refractory to the first line chemotherapy may be successfully treated with EP/EMA. Recent epidemiological data showed that women with complete hydatidiform moles could anticipate normal reproduction in the future. Studies found that pregnancies after treatment of molar pregnancy resulted in 69% full-term, live births; 8% premature deliveries; 1% ectopic pregnancies, and 0.5% stillbirths. First-trimester spontaneous abortions occurred in 17% of pregnancies, and major and minor malformations were detected in 0.4% of infants. Patients with hydatidiform mole were at increased risk of developing molar pregnancy in subsequent conceptions. After having one molar pregnancy, the risk of having molar disease in a future gestation was about 1%. The risk of persistent gestational trophoblastic tumors was increased by long-term oral contraceptive use before conception. In a large, multicenter, case-control study, the risk was shown to be increased in women who had ever used oral contraceptives, but was highest for women taking oral contraceptives during the cycle in which they became pregnant. Partial hydatidiform moles were never previously proven to transform into choriocarcinoma; however, a recent study with molecular techniques clearly showed that partial moles could transform into choriocarcinoma. All patients with suspected partial moles should be reviewed centrally and require hCG follow-up.

Gestational trophoblastic disease

In the past, it was seen as important not to get pregnant straight away after a GTD. Specialists recommended a waiting period of 6 months after the hCG levels become normal. Recently, this standpoint has been questioned. New medical data suggest that a significantly shorter waiting period after the hCG levels become normal is reasonable for approximately 97% of the patients with hydatidiform mole. Risk of a repeat GTD The risk of a repeat GTD is approximately 1 in 100, compared with approximately 1 in 1000 risk in the general population. Especially women whose hCG levels remain significantly elevated are at risk of developing a repeat GTD. Persistent trophoblastic disease The term «persistent trophoblastic disease» (PTD) is used when after treatment of a molar pregnancy, some molar tissue is left behind and again starts growing into a tumour. Although PTD can spread within the body like a malignant cancer, the overall cure rate is nearly 100%.

Placental site trophoblastic tumor arising from antecedent molar pregnancy.

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease. Little is known about its pathogenesis and natural history. This report describes two cases that arose in patients with documented complete hydatidiform moles and summarizes the antecedent prenatal histories of PSTTs based on a detailed Medline literature analysis. A 28-year-old, G(2)P(2) female had a live, 12-week gestation fetus and a coexisting molar pregnancy. Her hCG levels dropped promptly from 1.5 million to 23,273 IU/ml after termination, but rose shortly thereafter together with the onset of recurrent vaginal bleeding. Curettage revealed persistent mole. Persistently elevated hCG led to hysterectomy disclosing a fundal PSTT. The second case was that of a 48-year-old, G(2) woman who presented with symptoms of preeclampsia, hyperthyroidism, and elevated hCG. Curettage yielded a complete hydatidiform mole. Although the hCG level decreased for a short period, it soon increased despite treatment with methotrexate. A second curettage revealed a PSTT. A Medline literature analysis of PSTT, which consists almost entirely of individual cases and several small series, disclosed that PSTT is preceded in 61% of cases by normal term pregnancy, 12% molar pregnancy, 9% spontaneous abortion, 8% therapeutic abortion, and 3% with ectopic pregnancy, stillbirths or preterm delivery. No information is known in 7%. This report describes two additional cases of PSTT preceded by complete molar pregnancy. PSTT is a well recognized, but uncommon form of gestational trophoblastic disease. Although little is known about its pathogenesis, it is preceded not uncommonly by an abnormal pregnancy, including a molar pregnancy.

Occurrence of molar pregnancy in patients undergoing elective abortion: comparison with other clinical presentations.

Clinical data of molar pregnancies found in women undergoing elective abortion (group 1, n = 39) were compared to those of molar pregnancies in women who experienced spontaneous abortions (group 2, n = 157) and women in whom molar pregnancy was discovered before symptoms of spontaneous abortion were evident (group 3, n = 209). Group 1 women were younger and experienced uterine evacuation at an earlier stage of amenorrhea than groups 2 and 3. Group 3 had larger uteri at evacuation and longer intervals of positive tests for the beta-subunit of human chorionic gonadotropin during the postmolar phase as compared with groups 1 and 2. On the basis of available provincial data for the number of elective abortions, the estimated incidence of molar pregnancies in this population was 1:2,699. The presence of malignant gestational trophoblastic neoplasia was documented in a single patient in group 1. The incidence of malignant gestational trophoblastic neoplasia in this group was not significantly different from that in groups 2 and 3. Routine pathologic examination of the products of conception in women undergoing elective abortion coupled with routine assays of the beta-subunit of human chorionic gonadotropin when molar pregnancy is found can identify both noninvasive and invasive trophoblastic disease in these women.

Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy.

Complete hydatidiform molar pregnancies occur in approximately 1 of 1,000 conceptions. After uterine evacuation of the trophoblastic tissue, women are followed up with serial serum human chorionic gonadotropin (hCG) measurements. Patients are considered to have attained remission when their hCG level spontaneously declines to an undetectable level and remains there during a 6-month follow-up period. This standard effectively detects all disease recurrence; however, it is resource intensive, delays child bearing, and is subject to significant noncompliance. Our objective was to determine the risk of disease recurrence after hCG spontaneously declines to undetectable levels. We used a database from the New England Trophoblastic Disease Center to analyze hCG levels in patients with complete molar pregnancies. Among 1,029 women with complete molar pregnancy and complete data, 15% developed persistent gestational trophoblastic neoplasia. The rate of persistent neoplasm among those whose hCG level fell spontaneously to undetectable levels was 0.2% (2/876, 95% confidence interval 0-0.8%). No women developed persistent gestational trophoblastic neoplasia after their hCG level fell to undetectable levels using an assay with a sensitivity of 5 mIU/mL (n = 82, 95% confidence interval 0-4.5%). Based on our experience with women with complete hydatidiform molar pregnancies whose hCG values spontaneously fell to undetectable levels after molar evacuation, we conclude that the risk of recurrent neoplasm after hCG levels fall to less than 5 mIU/mL approaches zero.

[Studies on the viability of trophoblast after termination of various kinds of pregnancies (author's transl)].

Although normal value of hCG (LH level) does not necessarily indicate eradication of viable trophoblast, its confirmation has been demonstrated as a clinically useful guide for the probable prevention of choriocarcinoma after hydatidiform mole by Takeuchi et al. Choriocarcinoma preceded by other pregnancies than hydatidiform mole which has the highest risk for choriocarcinoma has drawn more attention than before in connection with the decrease of postmolar choriocarcinoma. So that I have studied the regression rate of urinary gonadotropin (hCG) after the termination of various kinds of pregnancies. In 2,433 cases of induced abortion, 695 cases of spontaneous abortion, 1,724 cases of term delivery and 43 cases of hydatidiform mole, their urinary hCG were determined to the level of physiological range of LH. The rate of hCG regression was in the order of term delivery, spontaneous abortion, induced abortion and hydatidiform mole. The younger was the gestational age of trophoblast, the slower was the regression of hCG. At one month after the termination of pregnancy, 80.1%, 11%, 0.3%, 8% and 4.1%, and at two month 55.8%, 1.6%, 0.5%, 4% and 0.5% for hydatidiform mole, induced abortion of less than 12 week of gestation, spontaneous abortion of less than 12 week of gestation, spontaneous abortion of between 13 and 20 week of gestation respectively still showed abnormal hCG value. One percent of induced abortion at 5 month, 4% of spontaneous abortion at 3 month, 0.3% of term delivery at 4 month still maintained abnormal titer. No malignant sequelae in patients under the investigation have ever been observed in the follow up period between 3 and 8 years.

Persistence of gestational trophoblastic disease for longer than 1 year following evacuation of hydatidiform mole.

A spontaneous fall in the radioimmunoassay for the beta subunit of hCG to less than 2 mIU/mL documents regression of hydatidiform mole following evacuation of a molar pregnancy. Continued negative hCG levels for the year after evacuation indicates the absence of risk for persistent gestational trophoblastic disease. This report describes an unusual case of recurrent nonmetastatic gestational trophoblastic disease 16 months after initial evacuation. A 29-year-old woman presented at 19 weeks' gestation with severe preeclampsia and vaginal bleeding. Pelvic ultrasonography demonstrated a molar pregnancy. Pathology following uterine evacuation confirmed a hydatidiform mole. Serial hCG levels fell progressively to less than 2 mIU/mL over the following 25 weeks. She remained compliant with oral contraceptive pills despite having no sexual activity. Sixteen months after uterine evacuation, recurrence of gestational trophoblastic disease was documented by a rising beta-hCG, negative pelvic ultrasound, normal liver function tests, and normal computed tomography of the head. Endometrial curettage showed no chorionic villi or molar tissue. She was treated with five courses of actinomycin D and has remained disease-free for the following 5 years. This late recurrence of gestational trophoblastic disease suggests that those with a molar pregnancy may benefit from surveillance beyond 1 year after uterine evacuation.

Gestational Trophoblastic Disease -- Epidemiology

Risk factors for molar pregnancy include extremes of age, ethnicity, and a prior history of a HM, suggesting a genetic etiology. The risk of a complete mole is higher for women older than 35 years and younger than 21 years and 7.5 times higher for women older than 40 years. The risk of repeat molar pregnancy in women with a history of molar pregnancy is approximately 1% which is 10 to 20 times the risk in the general population. [1] Interestingly, a history of prior spontaneous abortion has been reported to confer a 2- to 3-fold increased risk of molar pregnancy compared to women without a history of spontaneous abortion. [3] Following 2 molar gestations, the risk of having a third mole is > 10%. [7] It is also important to note that malignant transformation such as choriocarcinoma or placental-site trophoblastic tumor can occur following any pregnancy.

Postevacuation hCG levels and risk of gestational trophoblastic neoplasia in women with complete molar pregnancy.

Women diagnosed with complete hydatidiform molar pregnancy are at 15% to 28% risk of developing persistent gestational trophoblastic neoplasia (GTN) requiring further management with chemotherapy. Our objective was to develop human chorionic gonadotropin (hCG) criteria that establish a patient's risk of developing persistent GTN or achieving remission from their baseline risk within a few weeks of molar evacuation. We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 1,029 women with complete molar pregnancies. We conducted a retrospective cohort study using data from 1973 to 2001. Women whose hCG level declined below 50 mIU/mL during their follow-up were found to be at no more than 1.1% risk for developing persistent GTN, irrespective of when this level was reached. Women whose hCG levels was below 200 mIU/mL in the fourth week after evacuation (59.8% of all women), or below 100 mIU/mL in the sixth week after evacuation (65.8% of all women), had a risk of persistence below 9%. hCG levels above 2,000 mIU/mL in the fourth week after evacuation (13.3% of women) were associated with a 63.8% risk of developing persistent disease. These data may allow clinicians to evaluate the risk of persistence that their patients with complete molar pregnancy have based on early hCG results after molar evacuation. In the fourth week after molar evacuation, 59.8% of women may be counseled that their risk of developing persistent GTN is substantially reduced from their baseline, whereas 13.3% of women may be warned that their risk of developing persistent GTN is greater than 50%. II-2.

Increased frequency of complete hydatidiform mole in women with repeated abortion.

The association between spontaneous abortion and gestational trophoblastic disease (GTD) has been investigated in a study based on 93 women with 2 consecutive (repeated) spontaneous abortions and 82 control subjects who delivered normal babies. Nine molar pregnancies were observed among 7 of the 93 cases of repeated abortion while no control reported previous GTD. This difference was statistically significant and was not explained by allowance for age and number of pregnancies between cases and controls (chi 2(1) = 4.20; P = 0.04). When the observed number (9) of hydatidiform mole in the 385 pregnancies of the women with repeated abortion was compared with the expected one (0.28) based on the regional frequency data, the estimated relative risk was 32.1 with a 95% confidence interval from 13.9 to 63.3. The present findings confirm the association between GTD and spontaneous abortion and indicate that the risk is larger in women with repeated abortions.

[Reservation of fertility for seventeen patients with placental site trophoblastic tumor].

To approach the efficiency and feasibility of preserving the fertility for patients with placental site trophoblastic tumor (PSTT). Totally 2 086 cases of gestational trophoblastic neoplasm (GTN) patients registered in Peking Union Medical College Hospital between 1998 and 2013. Fifty-seven of them were PSTT patients, 40 cases of which suffered hysterectomy, the rest 17 PSTT patients who preserved their fertility were analyzed retrospectively. The computerized database of clinical and pathological reports was reviewed in this cohort. The clinical manifestation of PSTT was not specific compared to other types of GTN. The average age of the 17 patients was 29.5 years old (range 22-39 years). The most common antecedent pregnancy was term birth (8 cases), the others were spontaneous abortion in 4 case, artificial abortion in 3 cases and molar pregnancy in 2 cases. The baseline serum β-hCG was slightly elevated and 12 patients (12/15) were less than 1 000 U/L. In this cohort, nine of the patients were in stage I, while the other eight cases were in stage III . The patients suffered conservative surgery, including dilation and curettage of uterus in 7 cases, open abdomen uterine lesion excision in 4 cases, laparoscopic uterine lesion excision in 3 cases, hysteroscopic uterine lesion excision in 1 case, and pulmonary lobectomy in 2 cases. Two of the patients didn't received chemotherapy, while the other 15 cases suffered combination chemotherapy. Compared with 40 patients who suffered hysterectomy during the same interval, fertility preservation group did not result in poor outcomes or high risk of relapse rate. Six subsequent pregnancies happened after the therapy, two of them were during their second-trimester, while four patients had healthy babies by vaginal delivery in two and cesarean section in two. The scar of the uterus was fairly well during the cesarean sections. Reservation of fertility therapy could be considered in highly-selected patients for young women who strongly desired to preserve their fertility and with localized lesion. Exactitude follow-up after therapy should be recommended. Contraception should also be recommended for at least one year after the chemotherapy. Vaginal delivery could be an option for the future pregnancies.

Gestational trophoblastic disease

The use of a reliable contraception method is very important during the entire follow up period, as patients are strongly advised against pregnancy at that time. If a reliable contraception method is not used during the follow-up, it could be initially unclear to clinicians as to whether a rising hCG level is caused by the patient becoming pregnant again, or by the continued presence of GTD. In women who have a malignant form of GTD, hCG concentrations stay the same (plateau) or they rise. Persistent elevation of serum hCG levels after a non molar pregnancy (i.e., normal pregnancy [term pregnancy], or preterm pregnancy, or ectopic pregnancy [pregnancy taking place in the wrong place, usually in the fallopian tube], or abortion) always indicate persistent GTD (very frequently due to choriocarcinoma or placental site trophoblastic tumour), but this is not common, because treatment mostly is successful.

Persistent gestational trophoblastic disease is rarely, if ever, derived from non-molar first-trimester miscarriage.

Traditional epidemiologic data suggest that persistent gestational trophoblastic disease (pGTD), may follow, and be derived from, either molar pregnancy, non-molar term pregnancy or first-trimester non-molar miscarriage. We examined a database of cases of possible or probable hydatidiform moles and proven pGTD derived from the Regional Trophoblastic Disease Unit, Charing Cross Hospital, London. There were 424 cases (6%), in whom the initial registered diagnosis was that of PHM or CHM but central histopathological review diagnosed a definite non-molar hydropic abortion (HA). In eight of the 424 (2%), although the histology of the most recent index pregnancy was that of non-molar miscarriage, there was a previous history of pregnancy affected by hydatidiform mole; two of these developed subsequent pGTD. Of a further 86 cases referred for a histopathological opinion prior to registration which demonstrated definite non-molar HA, none developed pGTD (zero of 510 (0%, 95% CI 0-0.7%)). During the same period there were 352 cases with pGTD requiring chemotherapy. In 31 cases, the only known pregnancy was the preceding apparent non-molar HA. However, of these, there were only three cases in whom the preceding histological products of conception had been centrally reviewed and were suggestive of non-molar pregnancy. However, in all three of these cases, the specimens were inadequate for definite exclusion of molar pregnancy. In one case in whom no material was available for review, molecular genetic analysis using restriction fragment length polymorphisms was carried out, and the choriocarcinoma was genetically derived from a previous molar pregnancy rather than the preceding HA. There were therefore no cases identified on the database of the trophoblastic disease unit of pGTD requiring treatment in whom the trophoblastic tumour could be genetically proven to have arisen from the preceding first trimester non-molar HA. We suggest that the risk of pGTD developing from a histologically confirmed non-molar HA is less than 1 in 50,000 and that the majority of pGTD cases previously reported to have been caused by a non-molar miscarriage probably represent disease due to an unrecognised early molar pregnancy.

Gestational trophoblastic disease

In this scoring system, women with a score of 7 or greater are considered at high risk. It is very important for malignant forms of GTD to be discovered in time. In Western countries, women with molar pregnancies are followed carefully; for instance, in the UK, all women who have had a molar pregnancy are registered at the National Trophoblastic Screening Centre. There are efforts in this direction in the developing countries too, and there have been improvements in these countries in the early detection of choriocarcinoma, thereby significantly reducing the mortality rate also in developing countries. Becoming pregnant again Most women with GTD can become pregnant again and can have children again. The risk of a further molar pregnancy is low. More than 98% of women who become pregnant following a molar pregnancy will not have a further hydatidiform mole or be at increased risk of complications.

Gestational trophoblastic disease

However, the incidence of rare diseases (such as GTD) is difficult to measure, because epidemiologic data on rare diseases is limited. Not all cases will be reported, and some cases will not be recognised. In addition, in GTD, this is especially difficult, because one would need to know all gestational events in the total population. Yet, it seems very likely that the estimated number of births that occur at home or outside of a hospital has been inflated in some reports. Terminology Gestational trophoblastic disease (GTD) may also be called gestational trophoblastic tumour (GTT). Hydatidiform mole (one type of GTD) may also be called molar pregnancy. Persistent disease; persistent GTD: If there is any evidence of persistence of GTD, usually defined as persistent elevation of beta hCG (see «Diagnosis» below), the condition may also be referred to as gestational trophoblastic neoplasia (GTN). See also Trophoblastic neoplasms References External links

Pregnancy outcomes of patients who conceived within 1 year after chemotherapy for gestational trophoblastic tumor: a clinical report of 22 patients.

The aim of this study was to explore the risk of pregnancy of patients who conceived within 1 year after successful chemotherapy for gestational trophoblastic tumor (GTT). From 1966 to 1996, 22 patients who conceived within 1 year after chemotherapy were followed up and analyzed retrospectively. Among 22 patients, 9 had term deliveries and 1 had a premature birth, 6 had induced abortion at the patient's request, and 6 had therapeutic abortion because of various indications such as repeated hydatidiform mole (1 case), intrauterine death (1 case), inevitable abortion (1 case), and threatened abortion (3 cases). The fetal loss rate was 27.1% (6/22). The incidence rate of gestational trophoblastic disease (GTD) was 9.1% (2/22). The incidence rate of GTT was 4.5% (1/22). The average interval between completion of chemotherapy and pregnancy was 10.25 months in the group of term pregnancies and 5.86 months in that of fetal loss (P < 0.05), indicating that the longer the interval, the lesser the risk of GTD. The results suggest that contraception for 1 year is necessary in patients with GTT after successful chemotherapy. However, in the case of a patient who conceives within 1 year, it is not necessary to terminate pregnancy, but the pregnancy must be carefully watched.

Gestational trophoblastic disease

All five closely related tumours develop in the placenta. All five tumours arise from trophoblastic cells. The trophoblast is the membrane that forms the wall of the blastocyst in the early development of the fetus. In a normal pregnancy, trophoblastic cells aid the implantation of the fertilised egg into the uterine wall. But in GTD, they develop into tumour cells. Cause Two main risk factors increase the likelihood for the development of GTD: 1) The woman being under 20 years of age, or over 35 years of age, and 2) previous GTD. Although molar pregnancies affect women of all ages, women under 16 and over 45 years of age have an increased risk of developing a molar pregnancy.Being from Asia/of Asian ethnicity is an important risk factor. Hydatidiform moles are abnormal conceptions with excessive placental development. Conception takes place, but placental tissue grows very fast, rather than supporting the growth of a fetus.

Trophoblastic neoplasm

Management of GTN requires pathology review, treatment options and monitoring of hCG. Therefore, it can be treated with curettage, hysterectomy and single agent or multi agent chemotherapy. Although this group of diseases are highly susceptible to chemotherapy, prognosis depends on the type of GTN and whether the tumor has spread to other areas of the body. Cause and Risk factors The exact cause of gestational trophoblastic neoplasia (GTN) is unknown. GTN often arises after molar pregnancies but can also occur after any gestation including miscarriages and term pregnancies. Although risk factors may impact on the development of the tumor, most do not directly cause of disease. According to the some studies, the risk of complete molar pregnancy is highest in women over age 35 and younger than 20. The risk is even higher for women over age 45. Signs and Symptoms The symptoms of GTN will vary from person to person. People with the same disease may not have all the symptoms listed.

Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program.

Gestational Trophoblastic Neoplasia After Human Chorionic Gonadotropin Normalization Following Molar Pregnancy: A Systematic Review and Meta-analysis.

To estimate the incidence of gestational trophoblastic neoplasia following complete and partial molar pregnancy after reaching normal human chorionic gonadotropin (hCG) levels to guide evidence-based follow-up recommendations. MEDLINE, EMBASE, Web of Science, POPLINE, Cochrane, and ClinicalTrials.gov were searched from inception to November 2018, using the intersection of "gestational trophoblastic disease," "molar pregnancy," and "human chorionic gonadotropin" themes. Search results were screened to identify cohort studies of molar pregnancy reporting gestational trophoblastic neoplasia development, with at least 6 months of intended normal hCG follow-up. Two reviewers independently identified articles for inclusion. Data were extracted using a standardized form. For meta-analysis, cumulative incidence of gestational trophoblastic neoplasia, with CIs by the Agresti-Coull method, and pooled risk ratios (RRs) comparing complete and partial mole were calculated. Among the 19 eligible studies that reported adequate data for inclusion in the primary meta-analysis, we found low incidence of gestational trophoblastic neoplasia after normal hCG level following both complete mole (64/18,357, 0.35%, 95% CI 0.27-0.45%), and partial mole (5/14,864, 0.03%, 95% CI 0.01-0.08%). There was a significantly higher risk of gestational trophoblastic neoplasia after complete compared with partial molar pregnancy (RR 4.72, 95% CI 1.81-12.3, P=.002). Among gestational trophoblastic neoplasia cases after normal hCG level following complete mole, 89.6% occurred when the time from evacuation to normalization was 56 days or longer, and 60.7% were diagnosed beyond the commonly recommended 6-month surveillance interval. Sensitivity analyses, including those limiting to studies at low risk of bias, did not significantly affect results. We found an overall incidence of gestational trophoblastic neoplasia of 15.7% for complete mole (1,354/8,611, 95% CI 15.0-16.5%) and 3.95% for partial mole (221/5,593, 95% CI 3.47-4.50%). Gestational trophoblastic neoplasia development after normal hCG level following molar pregnancy is rare. Recommendations for frequency and duration of hCG follow-up can be minimized to lessen burden on patients and informed by the type of molar pregnancy and time interval from uterine evacuation to hCG normalization. PROSPERO, CRD42019116414.

Gestational trophoblastic neoplasia: A 6 year retrospective study.

To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score </=6) received single agent chemotherapy with methotrexate or actinomycin D. Patients with high risk (score >/=7) received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67%) achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27) achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27). Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

Surveillance for gestational trophoblastic neoplasia following molar pregnancy: a cost-effectiveness analysis.

Historically, published guidelines for care after molar pregnancy recommended monitoring human chorionic gonadotropin levels for the development of gestational trophoblastic neoplasia until normal and then for 6 months after the first normal human chorionic gonadotropin. However, there are little data underlying such recommendations, and recent evidence has demonstrated that gestational trophoblastic neoplasia diagnosis after human chorionic gonadotropin normalization is rare. We sought to estimate the cost-effectiveness of alternative strategies for surveillance for gestational trophoblastic neoplasia after human chorionic gonadotropin normalization after complete and partial molar pregnancy. A Markov-based cost-effectiveness model, using monthly cycles and terminating after 36 months/cycles, was constructed to compare alternative strategies for asymptomatic human chorionic gonadotropin surveillance after the first normal (none; monthly testing for 1, 3, 6, and 12 months; or every 3-month testing for 3, 6, and 12 months) for both complete and partial molar pregnancy. The risk of reduced surveillance was modeled by increasing the probability of high-risk disease at diagnosis. Probabilities, costs, and utilities were estimated from peer-reviewed literature, with all cost data applicable to the United States and adjusted to 2020 US dollars. The primary outcome was cost per quality-adjusted life year ($/quality-adjusted life year) with a $100,000/quality-adjusted life year willingness-to-pay threshold. Under base-case assumptions, we found no further surveillance after the first normal human chorionic gonadotropin to be the dominant strategy from both the healthcare system and societal perspectives, for both complete and partial molar pregnancy. After complete mole, this strategy had the lowest average cost (healthcare system, $144 vs maximum $283; societal, $152 vs maximum $443) and highest effectiveness (2.711 vs minimum 2.682 quality-adjusted life years). This strategy led to a slightly higher rate of death from gestational trophoblastic neoplasia (0.013% vs minimum 0.009%), although with high costs per gestational trophoblastic neoplasia death avoided (range, $214,000 to >$4 million). Societal perspective costs of lost wages had a greater impact on frequent surveillance costs than rare gestational trophoblastic neoplasia treatment costs, and no further surveillance was more favorable from this perspective in otherwise identical analyses. No further surveillance remained dominant or preferred with incremental cost-effectiveness ratio of <$100,000 in all analyses for partial mole, and most sensitivity analyses for complete mole. Under the assumption of no disutility from surveillance, surveillance strategies were more effective (by quality-adjusted life year) than no further surveillance, and a single human chorionic gonadotropin test at 3 months was found to be cost-effective after complete mole with incremental cost-effectiveness ratio of $53,261 from the healthcare perspective, but not from the societal perspective (incremental cost-effectiveness ratio, $288,783). Largely owing to the rare incidence of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization after molar pregnancy, prolonged surveillance is not cost-effective under most assumptions. It would be reasonable to reduce, and potentially eliminate, current recommendations for surveillance after human chorionic gonadotropin normalization after molar pregnancy, particularly among partial moles. With any reduction in surveillance, patients should be counseled on symptoms of gestational trophoblastic neoplasia and established in routine gynecologic care.

Placental site trophoblastic tumor

Placental site trophoblastic tumor is a form of gestational trophoblastic disease, which is thought to arise from intermediate trophoblast. It may secrete human placental lactogen (human chorionic somatomammotropin), and result in a false-positive pregnancy test. Placental site trophoblastic tumor is a monophasic neoplasm of the implantation site intermediate trophoblast, and usually a benign lesion, which comprises less than 2% of all gestational trophoblastic proliferations. Preceding conditions include molar pregnancy (5%). Compared to choriocarcinoma or invasive mole, hemorrhage is less conspicuous and serum β-HCG level is low, making early diagnosis difficult. Immunohistochemistry: Often stains with hPL, keratin, Mel-CAM, EGFR. Treatment Because chemotherapy is ineffective; the patient should undergo hysterectomy. Prognosis 10–20% of cases metastasize leading to death. References External links Health issues in pregnancy Germ cell neoplasia

Molar pregnancy

Etymology The etymology is derived from hydatisia (Greek "a drop of water"), referring to the watery contents of the cysts, and mole (from Latin mola = millstone/false conception). The term, however, comes from the similar appearance of the cyst to a hydatid cyst in an Echinococcosis. See also Gestational trophoblastic disease References External links Humpath #3186 (Pathology images) Clinically reviewed molar pregnancy and choriocarcinoma information for patients from Cancer Research UK MyMolarPregnancy.com: Resource for those diagnosed with molar pregnancy. Links, personal stories, and support groups. Germ cell neoplasia Pregnancy with abortive outcome

Guidelines following hydatidiform mole: a reappraisal.

The aim of this study was to determine how often patients with complete hydatidiform mole (CHM) who spontaneously achieve normal human chorionic gonadotrophin (hCG) levels subsequently develop persistent or recurrent gestational trophoblast disease. Four hundred and fourteen cases of CHM registered at the Hydatidiform Mole Registry of Victoria were reviewed retrospectively after molar evacuation. Maternal age, gestational age, gravidity and parity were determined for each patient, as well as the need for chemotherapy. Among the 414 patients, 55 (13.3%) required chemotherapy for persistent trophoblastic disease. None of the patients whose hCG levels spontaneously fell to normal subsequently developed persistent molar disease. Weekly hCG measurements are recommended for all patients until normal levels are achieved. For patients who attain normal hCG levels within 2 months after evacuation, it seems safe to discontinue monitoring once normal levels are achieved. Patients who fail to achieve normal hCG levels by 2 months after evacuation should be monitored with monthly hCG measurements for 1 year after normalisation to assure sustained remission.

Abortion

Complications after second-trimester abortion are similar to those after first-trimester abortion, and depend somewhat on the method chosen. The risk of death from abortion approaches roughly half the risk of death from childbirth the farther along a woman is in pregnancy; from one in a million before 9 weeks gestation to nearly one in ten thousand at 21 weeks or more (as measured from the last menstrual period). It appears that having had a prior surgical uterine evacuation (whether because of induced abortion or treatment of miscarriage) correlates with a small increase in the risk of preterm birth in future pregnancies. The studies supporting this did not control for factors not related to abortion or miscarriage, and hence the causes of this correlation have not been determined, although multiple possibilities have been suggested.

Postevacuation hCG levels and risk of gestational trophoblastic neoplasia among women with partial molar pregnancies.

To develop human chorionic gonadotropin (hCG) criteria that determine a patient's risk of developing persistent gestational trophoblastic neoplasia (GTN) or achieving remission after partial mole evacuation. We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 284 women with partial molar pregnancies diagnosed between 1973 and 2003. An hCG level >199 mIU/mL in the third through eighth week following molar evacuation was associated with at least a 35% risk of GTN. Women with partial mole who have elevated hCG levels within the first few weeks after molar evacuation are at increased risk for developing GTN.

Gestational trophoblastic disease: is intensive follow up essential in all women?

To determine the timescale of the registration process for gestational trophoblastic disease and its impact on hCG level at registration and subsequent need for chemotherapy. A prospective observational study using a standardised protocol for registration, assessment and treatment for molar pregnancy. A supra-regional tertiary referral centre for gestational trophoblastic disease. A total of 2046 consecutive women registered between January 1994 and December 1998 with a diagnosis of molar pregnancy. Data at and after registration, collected prospectively on a computerised database, were statistically analysed (by multiple logistic regression and ANOVA). Relationship between length of time to and hCG value at registration; also the subsequent need for chemotherapy. A total of 2046 women with a diagnosis of molar pregnancy were registered in the study period. The mean time interval between first evacuation and registration at the referral centre was 47 days (median 37, range 0-594). One hundred and five out of 2046 (5.1%) women needed chemotherapy. Sixty-three precent of the women (1296 out of 2046) had a normal level of urinary hCG (less than 40 IU/24 hours) at the time of registration and only one (0.08%) needed chemotherapy. Binary logistic regression analysis showed a statistically significant relationship between time to registration, hCG value, histology, pretreatment risk score and decision to administer chemotherapy. Women with gestational trophoblastic disease who were registered late were significantly more likely to have normal levels of hCG and were less likely to need chemotherapy. A less intensive follow up may be justified in women with gestational trophoblastic disease who are registered with a normal hCG level.

Persistent trophoblast disease following partial molar pregnancy.

Human chorionic gonadotrophin (hCG) follow-up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following partial molar pregnancy and to review the present follow-up protocol of patients suffering from partial hydatidiform molar pregnancy (PHM). Demographic factors were determined for all 344 cases with a review diagnosis of PHM, included age, history of previous hydatidiform mole, gestation length, hCG levels and compliance with follow-up. Six of the 344 patients diagnosed with PHM required treatment with single-agent methotrexate and folinic acid rescue. All six patients achieved and maintained a complete biochemical remission after chemotherapy. hCG regression assays were analysed for 235 patients: 225 patients had at least one normal hCG measurement during follow-up, of whom 152 (64.7%) patients obtained normal values within 2 months after evacuation. All patients obtained normal levels within 32 weeks after evacuation of the partial hydatidiform mole. Only 63 (25.6%) patients completed the recommended follow-up program. No patient who achieved normal hCG levels required chemotherapy because of a recurrent gestational trophoblastic tumour. This study indicates that 1.7% of all partial mole pregnancy patients needed treatment for malignant sequelae. In contrast, no patient diagnosed with partial mole had a biochemical or clinical relapse after achieving normal levels of hCG, consistent with previous studies. Patients who have had a partial hydatidiform mole should be followed by hCG assays until normal levels are achieved and then follow-up can be safely discontinued.

InternalMed_Harrison

(See Chap. 117) Gestational trophoblastic disease encompasses hydatidiform mole, choriocarcinoma, placental site trophoblastic tumor, and assorted miscellaneous and unclassifiable trophoblastic tumors. Moles are the most common, occurring in 1 in 1500 pregnancies in the United States. The incidence is higher in Asia. In general, if the serum level of β-human chorionic gonadotropin (β-hCG) returns to normal after surgical removal (evacuation) of the mole, the illness is considered gestational trophoblastic disease. By contrast, if the β-hCG level remains elevated after mole evacuation, the patient is considered to have gestational trophoblastic neoplasia. Choriocarcinoma occurs in 1 in 25,000 pregnancies. Maternal age >45 years and prior history of molar pregnancy are risk factors. A previous molar pregnancy makes choriocarcinoma about 1000 times more likely to occur (incidence 1–2%).

Obstentrics_Williams

Cormano ], Mackay G, Holschneider C: Gestational trophoblastic disease diagnosis delayed by the hook efect. Obstet GynecoIo126(4):811, 2015 Dantas PRS, Maesd. I, Filho ]R, et al: Does hormonal contraception during molar pregnancy follow-up influence the risk and clinical aggressiveness of gestational trophoblastic neoplasia after controlling for risk factors? Gynecol Oncol September 16, 2017 [Epub ahead of print] Davis MR, Howitt BE, Quade B], et al: Epithelioid trophoblastic tumor: a single institution case series at the New England Trophoblastic Disease Center. Gynecol Oncol 137(3):456,o20o15 Delmis ], Pfeifer 0, Ivanisecvic M, et al: Sudden death from trophoblastic embolism in pregnancy. Euro] Obstet Gynecol Reprod Bioi 92:225, 2000 de Medeiros SF, Norman RJ: Human chorionic gonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights. Hum Reprod Update 15(1):69,o2009

Gestational trophoblastic disease

Differential diagnosis These are not GTD, and they are not tumours Exaggerated placental site Placental site nodule Both are composed of intermediate trophoblast, but their morphological features and clinical presentation can differ significantly. Exaggerated placental site is a benign, non cancerous lesion with an increased number of implantation site intermediate trophoblastic cells that infiltrate the endometrium and the underlying myometrium. An exaggerated placental site may occur with normal pregnancy, or after an abortion. No specific treatment or follow up is necessary. Placental site nodules are lesions of chorionic type intermediate trophoblast, usually small. 40 to 50% of placental site nodules are found in the cervix. They almost always are incidental findings after a surgical procedure. No specific treatment or follow up is necessary. Treatment Treatment is always necessary.


A 27-year-old woman, 10 weeks pregnant, with persistent severe allergic asthma. She is currently adequately controlled with daily inhaled budesonide and rescue inhaled salbutamol on demand. She comes to your office concerned about the possible teratogenic effects of her anti-asthma medication. Which of the following would be the correct approach?

Given that asthma improves during pregnancy in most patients, the best thing for the patient and the fetus is to suspend anti-asthma treatment.

Discontinue budesonide because it has been associated with an increased risk of fetal malformations and replace it with an oral anti-leukotriene (montelukast).

Withdraw current treatment and replace it with oral prednisone at the lowest possible dose.

Maintain the current treatment and reassure the patient about its side effects and the need for adequate asthma control during pregnancy.

Replace budesonide with an anti-IgE monoclonal antibody (omalizumab) because of its greater safety in pregnancy since it is not a drug.

Managing asthma in expectant mothers.

Pregnancy does not appear to have a consistent effect on the frequency or severity of asthma. The most common cause of worsening asthma in pregnancy is likely to be noncompliance with medication. Emphasizing to the patient in advance that fetal well-being is dependent on maternal well-being may help prevent this.In general, well controlled asthma is not associated with a higher risk of adverse pregnancy outcomes. Essential to successful asthma management is patient education that helps to ensure effective medication use, avoidance of triggers, and prompt treatment. This education should include measurement of peak expiratory flow rate and a written asthma action plan. Most of the medications that are used to control asthma in the general population can be safely used in pregnant women. Inhaled beta-adrenoceptor agonists (beta-agonists), cromolyn sodium (sodium cromoglycate), and inhaled and systemic corticosteroids all appear to be very well tolerated by the fetus. Budesonide and beclomethasone should be considered as the preferred inhaled corticosteroids for the treatment of asthma in pregnancy. Use of the leukotriene receptor antagonists zafirlukast and montelukast in pregnancy is probably safe but should be limited to special circumstances, where they are viewed essential for asthma control. Zileuton should not be used in pregnancy.Acute asthma exacerbations in pregnant women should be treated in a similar manner to that in non-pregnant patients. Maternal blood glucose levels should be monitored periodically in pregnant women receiving systemic corticosteroids because of the deleterious effects of hyperglycemia upon embryos and fetuses. During pregnancy, maternal arterial oxygen saturations should be kept above 95% if possible for fetal well-being. Ambulatory oxygenation should be checked prior to discharge to ensure that women do not desaturate with their daily activities.Acute exacerbations of asthma during labor and delivery are rare. Dinoprost, ergometrine, and other ergot derivatives can cause severe bronchospasm, especially when used in combination with general anesthesia, and should be avoided in asthmatic patients. Pregnant women who have been treated with corticosteroids in the past year may require stress-dose corticosteroids during labor and delivery. Most asthma medications, including oral prednisone, are considered compatible with breast-feeding.

Outcome of pregnancy in a randomized controlled study of patients with asthma exposed to budesonide.

Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking. To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo. In a randomized, double-blind, placebo-controlled trial, 7241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 microg for adults. The study included 2473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for U.S. patients). Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes. Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.

Chapter 16: Asthma in pregnancy.

The course of asthma during pregnancy may be affected by maternal physiological changes and triggers of asthma such as viral infections, exposure to allergens, and nonadherence with therapy. If asthma is uncontrolled, there are recognized harmful effects not only to the mother but also  to the fetus. However, with effective asthma control, most women have outcomes, at or near that of the general population. Many medications are considered appropriate for use in pregnancy including inhaled corticosteroids (ICSs) such as budesonide, beclomethasone dipropionate, and fluticasone  and the leukotriene receptor antagonists montelukast and zafirlukast. When ICSs or ICS/long-acting beta(2)-adrenergic agonist combinations are not effective during exacerbations of asthma, short courses of oral corticosteroids should be administered earlier rather than later. Spirometry  and flow volume loop tracings are useful measures of pulmonary function for gravidas. Results may be compared with nonpregnant reference values. Vocal cord dysfunction may be suspected when the inspiratory loop is truncated. The gravida does not reject the fetus because of lack of vascular  continuity, a trophoblast layer causing separation, and suppressive mechanisms at the placental interface. The secretion of IL-10 increases in pregnancy and is lower in women with recurrent spontaneous abortions. Only immunoglobulin G (IgG) subclasses are transported across the placenta, especially  IgG1, IgG3, and IgG4. Fetal B cells can produce endogenous IgE by 20 weeks of gestation.

The management of asthma and rhinitis during pregnancy.

Asthma and rhinitis frequently complicate pregnancy. The course of asthma may be adversely altered by gestation, placing the mother and fetus at risk. Therefore, pregnant patients with persistent asthma require an aggressive asthma management plan that includes environmental control measures and the use of long-term controller medications. Inhaled corticosteroids (ICSs) are the preferred long-term controller medication for persistent asthma, based on efficacy. However, safety concerns regarding corticosteroids may cause physicians or patients to seek an alternate, less effective treatment during pregnancy. The Food and Drug Administration's pregnancy category ratings are based on animal and human safety data. Because ICSs were previously rated pregnancy category C (i.e., with human studies lacking and animal studies either lacking or positive for fetal risk), other asthma controllers, such as cromolyn and nedocromil, that carry a pregnancy category B rating (i.e., showing no evidence of fetal risk in humans or animal studies negative for fetal risk) appeared to be more desirable for use during pregnancy. One ICS, budesonide, was reclassified as pregnancy category B based on human data supporting its use during pregnancy. In moderate and severe persistent asthma, add-on therapy may be considered, including long-acting beta2-adrenergic agonists, leukotriene receptor antagonists, and theophylline. Because rhinitis may adversely affect quality of life and the course of asthma, recommendations for aggressive management also apply.

[Asthma and pregnancy -- efficacy and safety of medication during pregnancy].

Bronchial asthma is one of the most common medical problems in pregnancy, with prevalance around 4-7 %. Asthma clinical course is variable, with worsening of symptoms in one third of the cases. The most critical period occurs between the 24th and 36th week of gestation. Symptoms usually regress completely after delivery during the following three months and they are expected to recur, with the same pattern, in subsequent pregnancies. Asthma control during pregnancy depends on pregnant patient education and safe medication, preferably inhaled, that prevents crises. In chronic asthma, usually prescribed drugs (inhaled corticosteroids: beclometasone and budesonide) are effective and safe to the fetus. There are several drugs to be added to inhaled steroids -- beta agonists bronchodilators: short and long acting -- according to the severity of bronchial constriction and frequency of crises. Treatment of acute asthma should follow recommended guidelines, since uncontrolled asthma increases more the risk of pregnancy complications (low birth weight and premature delivery) than the eventual medication risks to pregnancy.

InternalMed_Harrison

Pregnancy Approximately one-third of asthmatic patients who are pregnant improve during the course of a pregnancy, one-third deteriorate, and one-third are unchanged. It is important to maintain good control of asthma because poor control may have adverse effects on fetal development. Compliance may be a problem because there is often concern about the effects of antiasthma medications on fetal development. The drugs that have been used for many years in asthma therapy have now been shown to be safe and without teratogenic potential. These drugs include SABA, ICS, and theophylline; there is less safety information about newer classes of drugs such as LABA, antileukotrienes, and anti-IgE. If an OCS is needed, it is better to use prednisone rather than prednisolone because it cannot be converted to the active prednisolone by the fetal liver, thus protecting the fetus from systemic effects of the corticosteroid. There is no contraindication to breast-feeding when patients are using these

Novel targets of omalizumab in asthma.

Omalizumab is a recombinant humanized anti-IgE monoclonal antibody approved in the US for moderate to severe persistent allergic asthma (severe persistent asthma in the European Union), uncontrolled despite treatment with inhaled corticosteroids and long-acting beta2 agonists. It reduces asthma exacerbations, symptoms, oral corticosteroid doses, and improves quality of life. Omalizumab may have an antiviral effect when used as a preventive therapy for fall exacerbations in children and teenagers. Two proof-of-concept studies have evaluated omalizumab in nonatopic asthma and showed that it is safe and possibly efficacious in some patients. Omalizumab has been successfully studied as add-on to specific immunotherapy in moderate allergic asthma. Its safety in pregnancy has been assessed in the EXPECT registry. Case series also report positive effects in cases of allergic bronchopulmonary aspergillosis, and in nasal disorders frequently associated with asthma. Last, omalizumab may have corticosteroid-sparing effect in a subset of patients with eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome). Recent studies argue in favor of positive effects of omalizumab beyond its current indications in asthma. Well-designed studies are needed in order to demonstrate the safety and efficacy of omalizumab in these possible novel indications.

Asthma

Leukotriene receptor antagonists (anti-leukotriene agents such as montelukast and zafirlukast) may be used in addition to inhaled corticosteroids, typically also in conjunction with a LABA. For adults or adolescents who have persistent asthma that is not controlled very well, the addition of anti-leukotriene agents along with daily inhaled corticosteriods improves lung function and reduces the risk of moderate and severe asthma exacerbations. Anti-leukotriene agents may be effective alone for adolescents and adults, however there is no clear research suggesting which people with asthma would benefit from anti-leukotriene receptor alone. In those under five years of age, anti-leukotriene agents were the preferred add-on therapy after inhaled corticosteroids. A 2013 Cochrane systematic review concluded that anti-leukotriene agents appear to be of little benefit when added to inhaled steroids for treating children. A similar class of drugs, 5-LOX inhibitors, may be used as an

Asthma

Mast cell stabilizers (such as cromolyn sodium) are safe alternatives to corticosteroids but not preferred because they have to be administered frequently. Oral Theophyllines are sometimes used for controlling chronic asthma, but their used is minimized because of their side effects. Omalizumab, a monoclonal Antibody Against IgE, is a novel way to lessen exacerbations by lessening the levels of circulating IgE that play a significant role at allergic asthma. Anticholinergic medications such as ipratropium bromide have not been shown to be beneficial for treating chronic asthma in children over 2 years old, but is not suggested for routine treatment of chronic asthma in adults.

Treatment of allergic rhinitis during pregnancy.

Allergic rhinitis is a frequent problem during pregnancy. In addition, physiological changes associated with pregnancy can affect the upper airways. Evidence-based guidelines on the management of allergic rhinitis have recently been published, the most recent being the Allergic Rhinitis and its Impact on Asthma (ARIA)--World Health Organization consensus. Many pregnant women experience allergic rhinitis and particular attention is required when prescribing drugs to these patients. Medication can be prescribed during pregnancy when the apparent benefit of the drug is greater than the apparent risk. Usually, there is at least one drug from each major class that can be safely utilised to control symptoms. All glucocorticosteroids are teratogenic in animals but, when the indication is clear (for diseases possibly associated, such as severe asthma exacerbation), the benefit of the drug is far greater than the risk. Inhaled glucocorticosteroids (e.g. beclomethasone or budesonide) have not been incriminated as teratogens in humans and are used by pregnant women who have asthma. A few histamine H(1)-receptor antagonists (H(1)-antihistamines) can safely be used as well. Most oral decongestants (except pseudoephedrine) are teratogenic in animals. There are no such data available for intra-nasal decongestants. Finally, pregnancy is not considered as a contraindication for the continuation of allergen specific immunotherapy.

Asthma

Corticosteroids are generally considered the most effective treatment available for long-term control. Inhaled forms are usually used except in the case of severe persistent disease, in which oral corticosteroids may be needed. Dosage depends on the severity of symptoms. High dosage and long term use might lead to the appearance of common adverse effects which are growth delay, adrenal suppression, and osteoporosis. Continuous (daily) use of an inhaled corticosteroid, rather than its intermitted use, seems to provide better results in controlling asthma exacerbations. Commonly used corticosteroids are budesonide, fluticasone, mometasone and ciclesonide.

Asthma

either because optimum doses of asthma medications do not work (called "refractory" asthma) or because individuals are either unable (e.g. inability to afford treatment, poor inhaler technique) or unwilling (e.g., wish to avoid side effects of corticosteroids) to take optimum doses of prescribed asthma medications (called "difficult to treat" asthma). In practice, it is not possible to distinguish "refractory" from "difficult to treat" categories for patients who have never taken optimum doses of asthma medications. A related issue is that the asthma efficacy trials upon which the pharmacological treatment guidelines are based have systematically excluded the majority of people with asthma. For example, asthma efficacy treatment trials always exclude otherwise eligible people who smoke, and smoking blunts the efficacy of inhaled corticosteroids, the mainstay of asthma control management.

Budesonide/formoterol

Common (≥1/100 to <1/10) side effects include candidiasis, headache, tremor, palpitations, throat irritation, coughing, and dysphonia. Pneumonia is a common side effect in people with COPD, and other, less common side effects have been documented. There were concerns that the LABA component increases the risk of death in children with asthma, however these concerns were removed in 2017. Therefore, this combination is only recommended in those who are not controlled on an inhaled steroid alone. There is tentative evidence that typical doses of inhaled steroids and LABAs are safe in pregnancy. Both formoterol and budesonide are excreted in breast-milk.

Montelukast

Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Other uses include allergic rhinitis and hives of long duration. For allergic rhinitis it is a second-line treatment. Common side effects include abdominal pain, cough, and headache. Severe side effects may include allergic reactions, such as anaphylaxis and eosinophilia. Use in pregnancy appears to be safe. Montelukast is in the leukotriene receptor antagonist family of medications. It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle.

Asthma in Pregnancy -- Treatment / Management

Salbutamol is the preferred reliever due to its high safety profile. Inhaled corticosteroids (ICS) are the preferred controller medications. It is safe to use ICS, theophylline, and montelukast during pregnancy. Prolonged use of systemic steroids has been associated with pregnancy-related complications, especially in the first trimester. But systemic steroids if indicated they should be used the same as in non-pregnancy (Evidence C). Research has suggested that management of asthma in pregnancy based on the fraction of exhaled nitric oxide (FENO) and symptoms significantly reduces asthma exacerbations. [9] In moderate-persistent asthma, a long-acting beta 2 agonist combined with an inhaled anti-inflammatory agent or inhaled corticosteroid is recommended for treatment. In severe asthma, oral corticosteroids and long-acting beta agonists are recommended. Inhaled glucocorticoids are relatively safe although there is a potential risk for endocrine and metabolic disturbances in fetuses. Sustained use of systemic steroids may increase the risk of congenital malformation, prematurity, neonatal insufficiency, low birth weight, preeclampsia, and gestational diabetes. [10] If anesthesia is indicated during labor, regional anesthesia is preferred. [11] [7]

Budesonide

Medical uses Asthma Budesonide is given by metered-dose inhaler or nebulizer for maintenance and prophylactic treatment of asthma, including patients who require oral corticosteroids and those who may benefit from a systemic dose reduction. Inflammatory bowel disease Formulations of delayed-release budesonide are an effective treatment for mild-to-moderately active Crohn's disease involving the ileum and/or ascending colon. A Cochrane review found evidence for up to three months (but not longer) of maintenance of remission in Crohn's disease. Budesonide assists in the induction of remission in people with active ulcerative colitis. Budesonide is highly effective and recommended as the drug of choice in microscopic colitis, for induction and maintenance of remission, and for both the lymphocytic colitis and collagenous colitis forms. Allergic rhinitis Budesonide in the form of nasal sprays is a treatment for allergic rhinitis.

Omalizumab in pregnant women treated due to severe asthma: two case reports of good outcomes of pregnancies.

The article presents case reports of 2 women who became pregnant during therapy with omalizumab. Both subjects suffered from very severe asthma and were treated chronically with all available medications including systemic steroids (first - 20 mg prednisolone/day, second - 40 mg prednisolone/day). Both were enrolled into treatment with omalizumab and started regular therapy in 2007. The course of asthma significantly improved in both cases (withdrawal of oral steroids or significant reduction of their dose, better asthma control). The first woman, 32-year-old, became pregnant in 2010 and gave birth in Oct 2010 - it was her 3(rd) pregnancy, and 3(rd) labor. The second woman, 31-year-old, also became pregnant in 2010 and gave birth in Jan 2011 - it was her 5(th) pregnancy and 2(nd) labor. Both had severe asthma exacerbations during previous pregnancies and labors, and decided to continue therapy with omalizumab. The first woman, besides omalizumab, was treated with high doses of inhaled corticosteroids (ICS) and long-acting β agonists (LABA) while the second one was treated with high doses of ICS, LABA and 2.5 mg to 5 mg prednisone/day. The pregnancies proceeded without asthma exacerbations. The first woman delivered a healthy girl (Apgar 9, weight 3200 g, length 56 cm) in the 40(th) week of pregnancy by caesarean section due to the narrow pelvis. The second one delivered a healthy boy (Apgar 9, weight 3800 g, length 56 cm) in week 40 by caesarean section due to the aggravating obstetrical history. In both cases, treatment with omalizumab did not affect pregnancies and newborns.

Hypersensitivity

Allergic bronchial asthma can be treated with any of the following: inhaled short- and long-acting bronchodilators (anticholinergics) along with inhaled corticosteroids, leukotriene antagonists, use of disodium cromoglycate, and environmental control. Experimentally, a low dose of methotrexate or cyclosporin and omalizumab (a monoclonal anti-IgE antibody) has been used. Treatment of autoimmune disorders (e.g., SLE) include one or a combination of NSAIDs and hydroxychloroquine, azathioprine, methotrexate, mycophenolate, cyclophosphamide, low dose IL-2, intravenous immunoglobulins, and belimumab. Omalizumab is a monoclonal antibody that interacts with the binding site of the high-affinity IgE receptor on mast cells. It is an engineered, humanized recombinant immunoglobulin. Moderate to severe allergic bronchial asthma can improve with omalizumab. Delayed hypersensitivity reactions Treatment of type 4 HR involves the treatment of the eliciting cause.

[A case of an asthma patient receiving omalizumab during pregnancy].

We describe the first report in Japan of a woman who received omalizumab during pregnancy and delivery. Her asthma was so severe that she had been taking systemic corticosteroids since 22 years old, but asthma was poorly controlled. She had been pregnant seven times before, but almost every time asthma control had worsened and spontaneous abortion resulted, so she had only one child. She confirmed that she was not intending to become pregnant, and initiated use of omalizumab in August 2009. However, pregnancy was identified after she had taken the drug 3 times. We explained the risks in detail, but the patient wanted to keep taking omalizumab, as her asthma control was improved and she thought she could continue the pregnancy. We therefore decided to continue with omalizumab therapy. In October, she caught a cold and experienced asthma exacerbation. Despite the risk, she decided to suspend omalizumab therapy after taking the drug 7 times, as she was not feeling any benefit from therapy. Threat of abortion was identified in February 2010, so a 544-g female baby was delivered at 26 weeks gestation by Cesarean section. The baby had to be hospitalized in the neonatal intensive care unit because of low birth weight, but she has been developing and growing without handicap. We report this case as the first known case of pregnancy and delivery for a woman receiving omalizumab in Japan. Omalizumab may be safe to use in pregnant women with difficult-to-control asthma.

Omalizumab: new drug. Asthma: too many unknowns for an anti-IgE.

(1) Long-term therapy for severe asthma (stage 4) currently consists of a high-dose inhaled steroid plus a long-acting beta-2 agonist. (2) Omalizumab is a recombinant anti-IgE antibody marketed for the treatment of severe allergic asthma associated with high circulating IgE levels, as an adjunct to inadequate ongoing treatment. Omalizumab is administered subcutaneously every 2 to 4 weeks. (3) Omalizumab has been evaluated in many clinical trials but only one, a double-blind randomised placebo-controlled trial lasting 28 weeks and involving 419 patients, corresponded to the approved indications. Omalizumab adjunction to ongoing treatment prevented one emergency department admission for asthma every 2.5 years on average, but this trial provided weak evidence as it suffered from several biases. In particular, the two groups were not identical at baseline in terms of prior frequency of asthma exacerbations. These were more frequent in the omalizumab group. In addition, many analyses were retrospective, few events occurred, and the protocol was modified 4 times. (4) A combined analysis of this and 4 other trials involving slightly different patients suggests that omalizumab prevents one asthma emergency approximately every 3 patient-years. (5) During comparative trials, the main adverse effects were anaphylaxis and local injection site reactions. Omalizumab may increase the risk of parasitic infections. Cases of laryngeal oedema and angioedema have been reported. (6) The possibility of an increased risk of cancer is to be examined in a post-marketing cohort study. (7) Treatment can cost more than 1700 euros a month. (8) In practice, in view of the potentially severe adverse effects of omalizumab, the evidence supporting its efficacy is too weak. It is better to carefully tailor existing treatments to the individual patient.

[A pregnant woman with severe asthma effectively treated by inhalational lidocaine therapy].

We report a case of a pregnant woman with severe asthma that was not controlled with ordinary medications but was effectively treated by inhalational lidocaine treatment. The case was a 27-year-old woman who had been repeatedly hospitalized due to acute asthma since her infancy. The patient had an episode of asthma attack caused by the use of aspirin. The daily medication for controlling her asthma included 1.5mg betamethasone. In February, 2004, she was hospitalized because of asthma exacerbation during her 11th week of pregnancy. Despite intensive treatments including repetition of inhaled beta2-agonist and anti-cholinergic drugs, intravenous injection of betamethasone and theophylline, and a leukotriene receptor-antagonist, no obvious improvement in severe cough, wheeze, or hypoxemia was observed for more than 3 weeks. Then inhalational lidocaine was introduced according to the method described by Mayo Clinic, USA. Namely, following inhalation of beta2-agonist, 40 to 100mg lidocaine was given via an ultrasonic nebulizer 5 times a day. Interestingly, symptoms such as wheezing or cough and also her hypoxemia dramatically improved following this treatment and reduction of systemic corticosteroid became possible. Finally, she was delivered of a girl by caesarean section. Nebulized lidocaine treatment may be an useful option as supplementary treatment for refractory asthma especially in pregnant cases.

Management of asthma during pregnancy.

Asthma is estimated to affect up to 4% of pregnancies. Management of asthma during pregnancy follows the same approach as in the general population. Aggressive treatment should be entertained because asthma under poor control during pregnancy can lead to poor outcomes for the mother and child. The foundations of management are environmental avoidance procedures, proper pharmacologic agents, and specific allergen immunotherapy. For pregnant women with persistent asthma, the use of inhaled cromolyn or inhaled budesonide should be considered as first-line agents. Short-acting beta-agonists can be used as needed in all asthma categories. Other agents such as salmeterol, leukotriene modifiers, newer inhaled corticosteroids, and omalizumab may be considered in women who showed a good response to these agents before pregnancy.

Case study: A Combination of Mepolizumab and Omaluzimab injections for severe asthma.

A Combination of Mepolizumab and Omaluzimab injections for severe asthma. Patients with severe persistent asthma account for a large proportion of asthma morbidity and health care expenditures. In this case report we describe the use of a combination of omalizumab and mepolizumab in severe asthma with elevated IgE levels and eosinophilic phenotype. We are treating a 55 year old woman with severe persistent eosinophilic asthma and elevated IgE levels. Her regimen included salmeterol/fluticasone propionate inhaler 500/50 one puff twice a day, budesonide nebulizer twice a day, tiotropium respimat inhaler two puffs daily, montelukast 10 mg daily, Albuterol as needed, Azithromycin 250 mg three times a week, and also omalizumab injections. She was having recurrent asthma exacerbations requiring the use of oral corticosteroids. Due to frequent exacerbations, we referred her for Bronchial Thermoplasty. This procedure was denied by insurance and therefore the patient was started on 20 mg PO prednisone daily. Mepolizumab was added approximately 4 months after starting chronic PO prednisone. We were able to taper down the steroids and she is currently on 4 mg daily. Since we added the mepolizumab injections along with the omalizumab injections, we have been able to decrease the prednisone steadily and currently the patient is on 4 mg daily. The plan is to taper off the corticosteroids slowly as the clinical status allows. Combination of omalizumab and mepolizumab could become the gold standard for severe asthma patients that have elevated IgE levels and an eosinophilic phenotype. A Combination of Mepolizumab and Omaluzimab injections for severe asthma.

Successful and safe treatment of severe steroid depended eosinophilic asthma with mepolizumab in a woman during pregnancy.

A 26-year-old female with steroid dependent eosinophilic asthma and nasal polyps who had successfully been treated with mepolizumab for 17 consecutive months with complete steroid withdrawal and symptoms control, stopped biologic treatment due to pregnancy efforts. Mepolizumab discontinuation resulted in frequent exacerbations and daily symptoms despite high dose ICS/LABA and re-initiation of oral steroids. Mepolizumab was initiated again, followed by improvement of asthma control and gradual withdrawal of steroids within 2 months. The patient became pregnant during the fourth month of mepolizumab re-initiation. The patient presented two asthma exacerbations during pregnancy treated with short course (3 days) oral steroids and delivery was uneventful (female, Apgar 9, weight 2750 g, length 59 cm) in week 40 by caesarean section.

Budesonide/formoterol

Use for both maintenance and as needed treatment is also known as single maintenance and reliever therapy ( SMART) and is a well-established treatment. It has been shown to reduce asthma exacerbations that require oral corticosteroids, hospital visits better than maintenance inhaled corticosteroids alone at a higher dose, or inhaled corticosteroid at the same or higher dose with a long acting bronchodilator (LABA)), with a short-acting bronchodilator (SABA) as a reliever. More studies using budesonide/formoterol SMART in children are needed. Side effects Common (up to 1 in 10 people) Mild throat irritation Coughing Hoarseness Oral candidiasis (thrush. significantly less likely if the patient rinses their mouth out with water after inhalations) Headache Often mild, and usually disappear as the medication continues to be used: Heart palpitations Trembling Uncommon (up to 1 in 100 people)

[Treatment of asthma during pregnancy].

Treatment of asthma during pregnancy leads to discussion concerning medication and complications of pregnancy.Insecurity about possible teratogenity leads in the first trimester in 40% of pregnant women to reduction or cessation of asthma medication.This results, in pregnant women with moderate to severe asthma, in an increased consumption of rescue medication and number of exacerbations, and reduced asthma control. Asthma-exacerbations are significantly correlated with low birthweight. Of the majority of asthma medications, consumption during pregnancy has not been shown to cause harmful effects on the foetus. Adequate therapy for maintenance and exacerbations are essential, noting that the treatment in essence should not differ between pregnant and nonpregnant asthmatic women. A preconceptional consultation by a pulmonary physician and gynaecologist could improve care for pregnant women with asthma.

Budesonide inhalation suspension: a review of its use in infants, children and adults with inflammatory respiratory disorders.

Budesonide, a topically active corticosteroid, has a broad spectrum of clinically significant local anti-inflammatory effects in patients with inflammatory lung diseases including persistent asthma. In infants and young children with persistent asthma, day- and night-time symptom scores, and the number of days in which beta2-agonist bronchodilators were required, were significantly lower during randomised, double-blind treatment with budesonide inhalation suspension 0.5 to 2 mg/day than placebo in 3 multicentre trials. Significantly fewer children discontinued therapy with budesonide inhalation suspension than with placebo because of worsening asthma symptoms in a study that included children who were receiving inhaled corticosteroids at baseline. Recent evidence indicates that budesonide inhalation suspension is significantly more effective than nebulised sodium cromoglycate in improving control of asthma in young children with persistent asthma. At a dosage of 2 mg/day, budesonide inhalation suspension significantly reduced the number of asthma exacerbations and requirements for systemic corticosteroids in preschool children with severe persistent asthma. In children with acute asthma or wheezing, the preparation was as effective as, or more effective than oral prednisolone in improving symptoms. In children with croup, single 2 or 4mg dosages of budesonide inhalation suspension were significantly more effective than placebo and as effective as oral dexamethasone 0.6 mg/kg or nebulised L-epinephrine (adrenaline) 4mg in alleviating croup symptoms and preventing or reducing the duration of hospitalisation. Early initiation of therapy with budesonide inhalation suspension 1 mg/day appears to reduce the need for mechanical ventilation and decrease overall corticosteroid usage in preterm very low birthweight infants at risk for chronic lung disease. In adults with persistent asthma, budesonide inhalation suspension < or =8 mg/day has been compared with inhaled budesonide 1.6 mg/day and fluticasone propionate 2 mg/day administered by metered dose inhaler. Greater improvements in asthma control occurred in patients during treatment with budesonide inhalation suspension than with budesonide via metered dose inhaler, whereas fluticasone propionate produced greater increases in morning peak expiratory flow rates than nebulised budesonide. Several small studies suggest that the preparation has an oral corticosteroid-sparing effect in adults with persistent asthma and that it may be as effective as oral corticosteroids during acute exacerbations of asthma or chronic obstructive pulmonary disease. The frequency of adverse events was similar in children receiving budesonide inhalation suspension 0.25 to 2 mg/day or placebo in 12-week studies. During treatment with budesonide inhalation suspension 0.5 to 1 mg/day in 3 nonblind 52-week studies, growth velocity in children was generally unaffected; however, a small but statistically significant decrease in growth velocity was detected in children who were not using inhaled corticosteroids prior to the introduction of budesonide inhalation suspension. Hypothalamic-pituitary-adrenal axis function was not affected by short (12 weeks) or long (52 weeks) term treatment with nebulised budesonide. In conclusion, budesonide inhalation suspension is the most widely available nebulised corticosteroid, and in the US is the only inhaled corticosteroid indicated in children aged > or =1 year with persistent asthma. The preparation is suitable for use in infants, children and adults with persistent asthma and in infants and children with croup.

Allergy Medications During Pregnancy.

Allergic diseases are common in women of childbearing age. Both asthma and atopic conditions may worsen, improve or remain the same during pregnancy. Primary care physicians commonly encounter women receiving multiple medications for pre-existing atopic conditions, who then become pregnant and require medication changes to avoid potential fetal injury or congenital malformations. Each medication should be evaluated; intranasal and inhaled steroids are relatively safe to continue during pregnancy (budesonide is the drug of choice), second-generation antihistamines of choice are cetirizine and loratadine, leukotriene receptor antagonists are safe, sparing use of oral decongestants during the first trimester and omalizumab may be used for both uncontrolled asthma and for antihistamine-resistant urticaria. Medications to avoid during pregnancy include intranasal antihistamines, first-generation antihistamines, mycophenolate mofetil, methotrexate, cyclosporine, azathioprine and zilueton. Common allergic diseases may develop de novo during pregnancy, such as anaphylaxis.

[The management of bronchial asthma during pregnancy--Hungarian experiences].

The prevalence of bronchial asthma is 4-8% among pregnant women. The complications, which threaten the asthmatic pregnancies according to the literature, are the following: spontaneous abortion, diabetes mellitus, caesarean delivery, pre-eclampsia, low gestational weight, neonatal icterus. The aim of the study was a retrospective analysis of the data of asthmatic pregnant patients managed between 2000 and 2004, with a special consideration on the treatment and gynecologic complications. The data of 53 persistent asthmatic patients--who had already undergone delivery--were collected. All of them were treated according to the guidelines issued in 2000 by the American College of Allergy, Asthma and Immunology and the American College of Obstetricians and Gynecologists: the inhalative corticosteroid budesonide, the long-acting beta-agonist formoterol or salmeterol and the short-acting beta-agonist terbutaline were used. The mean peak expiratory flow of the asthmatic pregnant patients was 71 +/- 16% of predicted, and the mean partial arterial oxygen tension 96 +/- 9 mmHg (means +/- SE). 10 of the 53 patients had cesarean delivery, 3 developed pre-eclampsia, 1 diabetes mellitus. The mean gestational age was 38.84 +/- 2.17 weeks and the weight of newborns 3132 +/- 604 g. The hospitalization was prolonged due to the infants' hyperbilirubinaemia in 3 cases. No congenital malformations or spontaneous abortions were detected. Based on the results of this retrospective study it can be concluded, that bronchial asthma slightly decreases the weight of newborns. The appropriate treatment of asthma during pregnancy resulted that the prevalence of gynecologic complications did not exceed the prevalence observed in the normal population--without increasing the risk of congenital malformations.

Mometasone/formoterol

It is not for the treatment of acute bronchospasm. To relieve acute symptoms, a rapid-onset short-duration inhaled bronchodilator (such as salbutamol) should be available. Warnings and precautions Long-acting β adrenoreceptor agonists (LABAs) are subject to a boxed warning against the possibility of an increased risk of asthma-related death. Formoterol belongs to the LABA class of drugs. As there does not exist at the time of the monograph's publication adequate research to determine whether the rate of asthma-related death is increased with formoterol, it is therefore recommended by the FDA that LABAs only be used for patients not adequately controlled on other asthma controlling medications or whose disease severity clearly warrants initiation of dual therapy.

Real-Life Benefit of Omalizumab in Improving Control of Bronchial Asthma During COVID-19 Pandemic.

Biologic therapy is recommended by Global Initiative for Asthma (GINA) guidelines in asthma patients not controlled with maximal inhaled therapy corresponding to GINA step 4. Omalizumab is an anti- immunoglobulin E (IgE) monoclonal antibody and the first biological available for the add-on treatment of severe allergic asthma, approved by Food and Drug Administration (FDA) in 2003. Diagnosing and managing asthma patients during coronavirus disease 2019 (COVID-19) pandemic since early 2020 has been challenging, mainly due to the risk of contracting COVID-19 disease and to the limited access to hospital care and pulmonary function tests. We report a case of a 52-year-old female patient, diagnosed with adult-onset asthma in 2018, who was first referred to the Allergy Department of our hospital in January 2019 for dyspnea, wheezing, and worsening cough. Despite continuous inhaled therapy and good inhalation technique, she had frequent asthma symptoms, requiring short courses of oral corticosteroids (CS). Physical examination and pulmonary function tests on admission revealed broncho-obstructive syndrome and laboratory tests showed mild inflammation and high total serum IgE. She continued to have two moderate-severe exacerbations after stepping up to maximal inhaled therapy plus oral montelukast and theophylline, according to GINA step 4. By the end of 2019, we additionally started omalizumab, which resulted in prompt clinical benefits and resolution of asthma symptoms. Given the ongoing COVID-19 pandemic limiting in-person visits, virtual follow-ups indicated adequate control of his symptoms, as proved by asthma control test and no need for hospital presentation.

What is safe enough - asthma in pregnancy - a review of current literature and recommendations.

Although asthma is one of the most serious diseases causing complications during pregnancy, half of the women discontinue therapy thus diminishing the control of the disease, mostly due to the inadequate education and fear of adverse events. Sadly, this is sometimes encouraged by insufficiently educated physicians. Since the incidence and the prevalence of asthma is increasing, it is important to arouse the importance of proper asthma therapy during pregnancy. Inadequate therapy, as well as interrupting or discontinuing therapy, may result in adverse perinatal outcomes for both mother and child. The main goal of asthma control during pregnancy is control of symptoms and prevention of exacerbations, same as in every asthmatic, but even more important. Maintaining optimal lung function, as well as regular daily activities, ensures maintenance of optimal fetal oxygenation. The therapy should be adapted depending on the frequency and severity of daily and nocturnal symptoms, demand for reliever therapy, by the limitations in everyday activities and the frequency of emergency asthma-related hospitalizations. Pre-conceptual education and therapy are very important and should be supported by an asthma action plan adjusted for the period of pregnancy. It is very important to note that most of the drugs used before pregnancy can be safely continued during pregnancy. Pharmacological and non-pharmacological therapy should be used in parallel. Pregnant women should be informed about the nature of the disease, therapy used during pregnancy, possible complications, avoidance of triggers, proper administration of therapy and, most important, why should the therapy be continued throughout the pregnancy on individual basis. Although drug treatment should be based on using drugs with less harm risk, if control of severe symptoms is needed to be achieved in order to protect both mother and child, any anti-asthmatic drug would have the beneficial benefit/harm ratio. There is no solid evidence that asthma treatment during pregnancy causes adverse outcomes for the mother and child but for many, especially new drugs, there is not enough data gathered. On the other hand, harmfulness of uncontrolled asthma during pregnancy is well documented so every effort should be put on preserving good control of asthma during pregnancy.