Veiligheid van astmamedicatie
Uitgangsvraag
Kan een vrouw tijdens zwangerschap veilig astmamedicatie blijven gebruiken (inclusief nieuwe medicatie, waaronder biologicals)?
De uitgangsvraag omvat de volgende submodules:
- Kortwerkende β2-sympathicomimetica (SABA)
- Langwerkende β2-sympathicomimetica (LABA)
- Parasympathicolytica (SAMA en LAMA)
- Inhalatiecorticosteroïden (ICS)
- Systemische corticosteroïden
- Leukotriëenreceptorantagonisten (LTRA, monteluklast)
- Biologicals (anti-IgE, anti-IL-5/5R, anti-IL-4)
Aanbeveling
Algemeen
Een goede astmacontrole door medicamenteuze behandeling tijdens de zwangerschap is veiliger en geeft minder complicaties dan het accepteren van astmasymptomen en exacerbaties.
Continueer medicatie bij de behandeling van een zwangere met astma, indien hier goede astmacontrole mee is bereikt.
Vraag bij voorschrijven van (nieuwe) astmamedicatie aan vrouwen met astma in de fertiele leeftijd uit of er sprake is van een actieve kinderwens om te beoordelen of een preconceptioneel advies gewenst is.
Vraag als voorschrijver of apotheker bij uitgifte van nieuwe medicatie aan vrouwen met astma in de fertiele leeftijd of er sprake is van een kinderwens of zwangerschap en pas de te geven informatie hierop aan.
Raadpleeg zo nodig de beschikbare actuele informatie op Teratologie Informatie Service (www.Lareb.nl) en Drugs and Lactation Database (LactMed) wanneer er vragen zijn over specifieke middelen (https://www.ncbi.nlm.nih.gov/books/NBK501922/).
Overwegingen
De overwegingen zijn opgesteld per groep astmamedicatie. Zie hiervoor de (sub)modules ‘Kortwerkende β2-agonisten’, ‘Langwerkende β2-agonisten’, ‘Parasympathicolytica (tiotropium, ipratropium)’, ‘Inhalatiecorticosteroïden’, ‘Systemische corticosteroïden’, ‘Leukotriëenreceptorantagonisten’ en ‘Biologicals’.
De onderstaande algemene aanbevelingen zijn gebaseerd op bestaande internationale richtlijnen over astma en zwangerschap en de literatuur die verder in de submodules aan bod komt.
Onderbouwing
Achtergrond
Bij de behandeling van een zwangere vrouw met astma moet een afweging gemaakt worden tussen het optimaal behandelen van astma en de veiligheid van het ongeboren kind. Uit literatuur is bekend dat onbehandeld astma een negatieve invloed heeft op het ongeboren kind (Bakhireva, 2008; Murphy, 2011). Onzekerheid rondom het al dan niet veilig kunnen gebruiken van astmamedicatie tijdens conceptie en zwangerschap kan leiden tot niet of onder-behandelen. Goede onderbouwing van veilig medicatiegebruik tijdens de zwangerschap en borstvoedingsperiode is nodig voor de zwangere en haar zorgverlener om samen tot de best passende medische behandeling te komen.
De werkgroep realiseert zich dat zwangere vrouwen met astma vaak ook klachten hebben van de bovenste luchtwegen. De veiligheid van medicatie voor zwangere vrouwen met een allergie van de bovenste luchtwegen (intranasale corticosteroïden en antihistaminicum sprays, orale antihistaminica, nasale decongestiva en (sublinguale of subcutane) allergeen immunotherapie) is door de werkgroep buiten het bestek van deze module gelaten. De werkgroep verwijst hiervoor naar de richtlijnen ‘Allergie van de bovenste luchtwegen (2020)’ (module ‘veilige middelen voor zwangere vrouwen’) en ‘Immunotherapie voor patiënten met allergische rhinoconjunctivitis (AR) met of zonder astma (2021)’.
Informatiebronnen met betrekking tot veiligheid van astmamedicatie tijdens de zwangerschap:
1) Moeders van Morgen is de overkoepelende naam van de Teratologie Informatie Service (TIS) en het zwangerschapsregister pREGnant. Het instituut is onderdeel van het Lareb en doet onderzoek naar en geeft informatie over geneesmiddelengebruik bij kinderwens en tijdens de zwangerschap en borstvoedingsperiode. Op de website www.lareb.nl is actuele informatie beschikbaar over of medicatie veilig is en met welke geneesmiddelen tijdens zwangerschap de meeste ervaring is opgedaan. Moeders van Morgen doet onder andere ervaring en kennis op door het verzamelen van ervaringen van zwangere vrouwen met behulp van online vragenlijsten waarvoor vrouwen zichzelf aan kunnen melden via de website www.moedersvanmorgen.nl .
2) Mother to baby is onderdeel van OTIS (Organization of Teratology Information Specialists) in de Verenigde Staten en wordt als informatiebron gebruikt door o.a. het CDC (Centre for Disease Control and Prevention) en de FDA (Food and Drug Administration’s office of women’s health). Mother to baby verstrekt evidence-based informatie over veiligheid van medicatie tijdens zwangerschap en borstvoeding. Daarnaast is er op de website van Mother to baby begrijpelijke informatie te vinden voor patiënten over de veiligheid van nagenoeg alle astmamedicatie (inclusief nieuwe biologicals) tijdens de zwangerschap. Tenslotte maken de meeste ‘pregnancy exposure studies’ deel uit van Mother to baby.
Samenvatting literatuur
Analysis of literature was performed for different groups of asthma medication. For the summary of literature for each specific group please see ‘Summary of literature’ in (sub)modules ‘Short-acting β2-agonists’, ‘Long-acting β2-agonists’, ‘Tiotropium and ipratropium’, ‘Inhaled corticosteroids’, ‘Oral corticosteroids’, ‘Leukotriene receptor antagonists’, ‘and ‘Biologicals’.
Zoeken en selecteren
A systematic review of the literature was performed to answer the following question:
What is the risk of neonatal and maternal complications in women with asthma taking asthma medication during pregnancy, compared to not taking these medications, and compared to pregnant women without astma?
PICO1:
P (patients): Pregnant women with asthma
I (intervention): Use (or continuation) of asthma medication
C (control): No use (or discontinuation of) asthma medication
O (outcomes): Major congenital malformations, small for gestational age, low birth weight, preterm birth, pregnancy-induced hypertension, spontaneous abortion, stillbirth
PICO2:
P (patients): Pregnant women with asthma
I (intervention): Use of asthma medication
C (control): Pregnant women without astma (not using astma medication)
O (outcomes): Major congenital malformations, small for gestational age, low birth weight, preterm birth, pregnancy-induced hypertension, spontaneous abortion, stillbirth
The following groups of asthma medication were included in the PICO-question: short-acting β2-agonists, long-acting β2-agonists, tiotropium and ipratropium, inhaled corticosteroids, oral corticosteroids, leukotriene receptor antagonists and biologicals.
Note that the following groups of supporting medication for women with asthma were excluded from the PICO question because they are beyond the scope of this module: intranasal corticosteroids, intranasal antihistamines, oral antihistamines, nasal decongestants and (sublingual or subcutaneous) allergen immunotherapy.
Relevant outcome measures
The guideline development group considered ‘major congenital malformations’, ‘small for gestational age’, ‘low birth weight’, ‘preterm birth’, and ‘pregnancy-induced hypertension’ as critical outcome measures for decision making; and outcomes, ‘stillbirth’ and ‘spontaneous abortion’ as important for decision making.
A priori, the working group did not define the outcome measures listed above but used the definitions used in the studies.
The working group used the GRADE standard limit of 25% difference for dichotomous outcomes (RR <0.8 or >1.25) and 10% for continuous outcomes as a minimal clinically (patient) important difference.
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from 01 January 1960 until 17 August 2020. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 646 hits. Studies were selected based on the following criteria: systematic reviews (with meta-analyses), randomized controlled trials (RCTs) and observational studies, answering the PICO-question. Studies were initially selected based on title and abstract screening. Eighty-six studies were selected based on title and abstract screening. After reading the full text, 71 studies were excluded (see the table with reasons for exclusion under the tab Methods), and 15 studies were included.
Results
Three systematic reviews (SRs) that investigated the effect of asthma medication on neonatal and maternal complications were included in the analysis of literature (Rahimi, 2006; Murphy, 2013; Namazy, 2013). Additionally, 10 observational studies were included: 7 of them described the use of short-acting β2-agonists during pregnancy (Vasilikas-Scaramoza, 2013; Garne, 2016; Lin, 2009; Eltonsy, 2011; Kallen 2007; Tata, 2008; Bracken, 2003), 5 studies - the use of long-acting β2-agonists (Vasilikas-Scaramoza, 2013; Eltonsy, 2011; Kallen 2007; Tata, 2008; Bracken, 2003); 0 studies - the use of parasympathicolytics, 4 studies - the use of inhaled corticosteroids (Blais 2007; Tata, 2008; Vasilakis-Scaramozza, 2013; Bakhireva, 2005), 4 studies -the use of oral corticosteroids (Tata, 2008; Garne, 2016; Vasilakis-Scaramozza, 2013 Bakhireva, 2005), and 2 studies - the use of leukotriene receptor antagonists (Cavero-Carbonell, 2017; Bracken, 2003). There were no comparative studies assessing the use of biologicals with neonatal and maternal complications in women with asthma. A summary of 2 descriptive studies reporting on the use of omalizumab during pregnancy (Namazy, 2015; Namazy, 2020) was made to provide relevant data for the recommendations. Important study characteristics and results are summarized in the evidence tables. The assessment of risk of bias is summarized in the risk of bias tables.
Referenties
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- Källén, B., & Olausson, P. O. (2007). Use of anti-asthmatic drugs during pregnancy. 3. Congenital malformations in the infants. European journal of clinical pharmacology, 63(4), 383-388.
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Evidence tabellen
1. Evidence table for systematic review of RCTs and observational studies (intervention studies)
|
Study reference |
Study characteristics |
Patient characteristics |
Intervention (I) |
Comparison / control (C)
|
Follow-up |
Outcome measures and effect size |
Comments |
|
Namazy, 2013 |
SR and meta-analysis of cohort and case-control studies
Literature search from January 1975 to March 2012
A: Stenius-Aarnaiala, 1996 B: Murphy, 2005 C: Jana, 1995 D: Dombrowski, 2004 E: Greenberger, 1988 F: Schatz, 2005 G: Schatz, 2004 H: Kallen, 2007 I: Firoozy, 2011
Study design: 10 cohort studies, but only 2 (F,G) reported on a relationship between OCS use and perinatal outcome
Setting and Country: F: USA, hospital G: USA, hospital
Source of funding and conflicts of interest: Not reported for the individual studies
|
Inclusion criteria SR: cohort studies that contained data comparing perinatal outcomes of interest in groups of asthmatic patients stratified by history of exacerbations, OCS use or asthma severity
Exclusion criteria SR: Not fulfilling inclusion criteria
9 studies included
Important patient characteristics at baseline:
For studies F,G n=267 cases used OCS during pregnancy
n=2341 controls did not use OCS during pregnancy
|
Describe intervention F,G = OCS use during pregnancy |
Describe control F,G = No OCS use during pregnancy |
End-point of follow-up No follow-up, retrospective cohort studies
For how many participants were no complete outcome data available? (intervention/control)
Not applicable . |
Outcome
Pre-term delivery (n/N) Exposed 49/267 Unexposed 320/2341 RR=1.51; 95% CI 1.15–1.98
Low birth weight (n/N) Exposed OCS 39/267 Unexposed OCS = 272/2341 RR=0.81; 95% CI 0.48–1.34
Small for gestational age (n/N) Exposed OCS 16/267 Unexposed OCS = 169/2241 RR 0.81; 95% CI 0.48–1.34 |
Facultative:
The authors conclude that oral corticosteroid may be associated with pre-term delivery. |
|
Rahimi, 2016 |
SR and meta-analysis of cohort and case-control studies
Literature search from January 1997 to December 2005
A: Bracken, 2003 B: Schatz, 2004 C: Martel, 2005 D: Otsuka, 2005
Study design: 4 cohort studies,
Setting and Country: Not described
Source of funding and conflicts of interest: Not reported
|
Inclusion criteria SR: exposure of women to any therapeutic dosage of any ICs (fluticasone, beclomethasone, budesonide, triamcinolone and flunisolide) during pregnancy
Exclusion criteria SR: Studies that were reviews, had not investigated the effects of ICs alone, had not determined our desirable outcomes, did not have a control group or had a control group made up of non-asthmatic women were excluded
4 studies included
Important patient characteristics at baseline: (exposed/nonexposed)
Major malformations (n/N) B Exposed = 14/722 Unexposed = 8/1401 D Exposed = 0/125 Unexposed = 0/100
Preterm delivery (n/N) A Exposed = 15/176 Unexposed = 136/2029 B Exposed = 140/722 Unexposed = 277/1401 D Exposed = 3/125 Unexposed = 6/100
Low birth weight (n/N) A Exposed = 8/136 Unexposed = 159/2065 B Exposed = 94/722 Unexposed = 197/1401
Pregnancy-induced hypertension B Exposed = 81/722 Unexposed = 164/1401 C Exposed = 150/1553 Unexposed = 152/1762 D Exposed = 0/125 Unexposed = 10/100
|
Describe intervention Asthmatic women exposed to inhaled corticosteroids during pregnancy |
Describe control Asthmatic women unexposed to inhaled corticosteroids during pregnancy |
End-point of follow-up No follow-up, cohort studies
For how many participants were no complete outcome data available? (intervention/control)
Not applicable . |
Outcome Major malformations; OR (95%CI) B= 0.97 (0.47, 1.92) D= 0.80 (0.00, 31.26) Overall= 0.96 (0.51, 1.83)
Pre-term delivery; OR (95%CI) A= 1.30 (0.69, 2.28) B= 0.98 (0.77, 1.23) D= 0.39 (0.06, 1.87) Overall= 0.99 (0.80, 1.22)
Low birth weight OR (95%CI) A= 0.75 (0.31, 1.56) B= 0.91 (0.69, 1.20) Overall = 0.89 (0.70, 1.14)
Pregnancy induced hypertension; OR (95% CI) B= 0.95 (0.71, 1.27) C= 1.13 (0.89, 1.45) D= 0.03 (0.00, 0.30) Overall = 0.97 (0.63, 1.48)
|
Facultative:
The authors conclude that ICs do not increase the risk of major malformations, preterm delivery, low birth weight and pregnancy-induced hypertension |
|
Murphy, 2013 |
SR and meta-analysis of cohort and case-control studies
Literature search from January 2009 to March 2012
Study design: 21 cohort studies
Setting and Country: See murphy (2013) table S1 for characteristics of the included studies
Source of funding and conflicts of interest: Not reported
|
Inclusion criteria SR: exposure of women to any therapeutic dosage of any ICs (fluticasone, beclomethasone, budesonide, triamcinolone and flunisolide) during pregnancy
Exclusion criteria SR: Studies that were reviews, had not investigated the effects of ICs alone, had not determined our desirable outcomes, did not have a control group or had a control group made up of non-asthmatic women were excluded
4 studies included
Important patient characteristics at baseline: (exposed/nonexposed)
See murphy (2013) table S1 for characteristics of the included studies
|
Describe intervention See murphy (2013) table S1 for characteristics of the included studies
|
Describe control Unexposed asthmatic women |
End-point of follow-up No follow-up, cohort studies
For how many participants were no complete outcome data available? (intervention/control)
Not applicable . |
Outcome weight loss
Congenital malformations RR=0.96 [0.89–1.04]
Stillbirth RR=0.77 [0.50–1.18]
|
Facultative:
The authors conclude that there is a small increased risk of neonatal complications among pregnant women with asthma. |
2. Evidence table for intervention studies (randomized controlled trials and non-randomized observational studies [cohort studies, case-control studies, case series])1
|
Study reference |
Study characteristics |
Patient characteristics 2 |
Intervention (I) |
Comparison / control (C) 3
|
Follow-up |
Outcome measures and effect size 4 |
Comments |
|
Vasilakis-Scaramozza, 2013 |
Type of study: Matched cohort study
Setting and country: United Kingdom
Funding and conflicts of interest: Not reported |
Inclusion criteria: Women were included aged 15–45, full year of medical history prior to inclusion. Diagnosis of asthma at any time before or during the pregnancy, as well as at least one prescription for an asthma drug noted during the first trimester of pregnancy or within 4 weeks of the estimated first day of the last menstrual period
Pregnancies occurred from January 1991–April 2002
Exclusion criteria: Multiples pregnancies for live births and stillbirths were excluded
N total at baseline: Exposed: n=7911 Unexposed: n=15,840
Important prognostic factors2: (Unexposed (%)/exposed (%))
Pre-pregnancy BMI <25=7790 (49.2)/3568 (45.1) 25-29=3304 (20.9)/2234 (28.2) >30=53 (0.3)/79 (1.0)
Maternal age <35 13,829 (87.3)/6872 (86.9)
Nonsmoker 7998 (50.5)/4097 (51.8)
Smoker 4110 (26.0)/2191 (27.7)
History of diabetes 92 (0.6)/45 (0.6)
Insulin use 54 (0.3)/16 (0.2)
Teratogen exposure 40 (0.3)/30 (0.4)
History of infertility 150 (1.0)/73 (0.9)
Premature delivery 66 (0.4)/37 (0.5)
|
Describe intervention:
Women exposed to asthma medication during the during the first trimester of pregnancy or within 4 weeks of the estimated first day of the last menstrual period
|
Describe control:
Women with no exposure to asthma drugs and who did not have a diagnosis of asthma in their medical records were matched in a 2:1 ratio to women exposed to asthma drugs during pregnancy by age, year of pregnancy outcome, and general practice |
Length of follow-up: Cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
Musculoskeletal anomalies Short-acting b agonist RR=1.0 (0.5–2.1)
Long-acting b agonist RR=1.9 (0.4–9.1)
Inhaled corticosteroids RR=1.2 (0.5–2.5)
Oral corticosteroids RR=1.1 (0.2–5.2)
Cleft lip or palate Short-acting b agonist RR=1.4 (0.5–4.1)
Long-acting b agonist RR=2.4 (0.3–21.8)
Inhaled steroid RR=0.7 (0.2–2.6)
Oral steroid RR=1.3 (0.1–14.0)
Cardiovascular anomalies Short-acting b agonist RR=1.3 (0.8–2.1)
Long-acting b agonist RR=1.0 (0.2–4.4)
Inhaled steroid RR=1.0 (0.6–1.7)
Oral steroid RR=0.9 (0.3–3.2)
Multiple anomalies Short-acting b agonist RR=1.2 (0.6–2.2)
Long-acting b agonist RR=1.4 (0.3–6.3)
Inhaled steroid RR=1.6 (0.8–3.2)
Oral steroid RR=0.9 (0.2–3.9) |
The authors conclude that that asthma drugs do not increase the risk of congenital anomalies in the offspring when taken during the first trimester of pregnancy.
|
|
Cavero-Carbonell, 2017 |
Type of study: Cross-sectional cohort study
Setting and country: Denmark
Funding and conflicts of interest: Not conflict of interest.
No funding reported |
Inclusion criteria: Pregnancies >12 weeks of gestation; live births and stillbirths; living in Denmark for 1 year before last menstrual period and 1 year after pregnancy; montelukast exposure
Exclusion criteria: Multiples pregnancies for live births and stillbirths were excluded
N total at baseline: Exposed: n=401 Unexposed: n=728,595
Important prognostic factors2: (Unexposed (%)/exposed (%))
Smoking 127,161 (17.4)/73 (18.2)
Age <21 = 23,153 (3.2)/18 (4.5) 21-30=395,715 (54.3)/200 (49.9) 31-40=299,881 (41.2)/179 (44.6) >40=9,846 (1.3)/4 (1.0)
Hospital diagnosis of asthma 12,072 (1.7)/214 (53.4) |
Describe intervention:
Women exposed to montelukast in the timespan from 3 months before last menstrual period to end of first trimester.
|
Describe control
Women not exposed to montelukast |
Length of follow-up: Cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
Major congenital anomaly (n) Congenital cataract = 0 Congenital heart defects = 11 Respiratory = 0 Oro-facial clefts = 0 Digestive system = 4 Genital = 3 Urinary = 3 Limb = 5
Odds Ratio for Major Congenital Anomaly compared to unexposed.
OR=1.4 (0.9–2.3) |
The authors conclude that Pregnant women with prescriptions for montelukast had a higher risk of preterm birth and maternal complications. |
|
Blais, 2007 |
Type of study: Retrospective cohort study
Setting and country: Canada
Funding and conflicts of interest: Funded by non-commercial organisations
Authors co-chair Endowment Pharmaceutical Chair AstraZeneca
|
Inclusion criteria: At least one pregnancy; aged 12-44; diagnoses of asthma (ICD-9 code 493); covered by RAMQ drug insurance plan.
Exclusion criteria: Not fulfilling inclusion criteria
N total at baseline: Total: n=4561 Malfomation cases: n=418
Important prognostic factors2: (Total (%)/case (%))
Age <18 = 736 (16.1)/41 (5.6) 19-34=3556 (78.0)/220 (6.2) >35=269 (5.9)/17 (6.3)
Received social assistance 4128 (90.5)/260 (6.3)
Urban area of residence 3752 (82.3)/238 (6.3)
Multiple pregnancy 61 (1.3)/15 (24.6)
Diabetes mellitus 97 (2.1)/11 (11.3)
Epilepsy 38 (0.8)/9 (23.7)
|
Describe intervention:
Women exposed to astma medication during the first trimester.
|
Describe control
Women not exposed to asthma medication |
Length of follow-up: Cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
Use of ICS (µg/day); OR (95% CI) >0–500=0.77 (0.53 to 1.13) >500-1000=0.41 (0.19 to 0.92) >1000=1.00 (0.42 to 2.36)
Oral corticosteroids use; OR (95% CI) 1.93 (0.94 to 3.98) |
The authors conclude that results of this study confirm the recommendation made by the guidelines on the treatment of asthma during pregnancy as to the use of ICS to maintain asthma under control and reduce the risk of adverse perinatal outcomes |
|
Garne, 2016 |
Type of study: Meta-analysis of aggregated data from three cohort studies.
Setting and country: Norway, Wales, Denmark
Funding and conflicts of interest: Funded by provided by the European Union under the Seventh Framework Programme |
Inclusion criteria: all liveborn infants, stillbirths/ late fetal deaths after 20 completed weeks of gestation in the three populations and terminations of pregnancies at any GA due to fetal anomaly (TOPFA) recorded in the EUROCAT registry, with delivery date or date of termination between 1 January 2000 and 31 December 2010.
Exclusion criteria: Not fulfilling inclusion criteria
N total at baseline: Total: n=519,242 Exposed to asthma medication: n=19,510
Important prognostic factors2: (Unexposed/Exposed)
Denmark Live birth; % 99.0/99.2
Stillborn; % 0.8/0.6
TOPFA; % 0.2/0.2
Maternal age in years; mean (SD) 29.3 (4.8)/ 29.0 (4.8)
Current smoker; % 18.2/16.7
Maternal BMI <25: 36.5/40.1 25-29: 14.0/14.2 30+: 12.4/8.0 Unknown: 37.1/37.6
Norway Live birth; % 99.3/99.3
Stillborn; % 0.5/0.5
TOPFA; % 0.2/0.2
Maternal age in years; mean (SD) 29.8 (5.3)/ 29.7 (5.1)
Current smoker; % 17.8/11.5
Maternal BMI <25: 12.2/14.6 25-29: 5.8/4.9 30+: 4.5/2.6 Unknown: 77.5/77.9
Wales Live birth; % 98.9/99.1
Stillborn; % 0.6/0.4
TOPFA; % 0.5/0.5
Maternal age in years; mean (SD) 27.8 (6.1)/ 28.3 (6.1)
Current smoker; % 33.7/29.3
Maternal BMI <25: 36.1/37.8 25-29: 18.3/15.6 30+: 17.6/10.6 Unknown: 28.0/36.0 |
Describe intervention:
Women exposed to astma medication during the first trimester.
|
Describe control
Women not exposed to asthma medication |
Length of follow-up: Cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
Inhaled beta-2-agonists; OR (99% CI) Norway: 1.22 (1.02–1.46) Wales: 1.21 (1.02–1.43) Denmark: 1.18 (0.77–1.81) Meta: 1.19 (1.06–1.34)
Short-acting beta-2-agonists; OR (99% CI) Norway: 1.21 (1.01–1.46) Wales: 1.22 (1.03–1.45) Denmark: 1.12 (0.71–1.77)) Meta: 1.19 (1.06–1.35)
Long-acting beta-2-agonists; OR (99% CI) Norway: 1.24 (0.71–2.19) Wales: 1.03 (0.52–2.05) Denmark: 1.56 (0.6–4.05) Meta: 1.22 (0.82–1.82)
Inhaled corticosteroids; OR (99% CI) Norway: 1.12 (0.78–1.59) Wales: 1.26 (1.00–1.6) Denmark: 0.98 (0.54–1.77) Meta: 1.20 (1.00–1.44)
Combination treatments; OR (99% CI) Norway: 1.16 (0.92–1.47) Wales: 1.19 (0.84–1.68) Denmark: 1.78 (0.98–3.23) Meta: 1.21 (1.00–1.45)
Systemic corticosteroids; OR (99% CI) Norway: 1.60 (0.92–2.79) Wales: 1.40 (0.8–2.45) Denmark: 1.71 (0.00–6.96)) Meta: 1.48 (1.01–2.17)
|
The authors conclude that increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status |
|
Lin, 2009 |
Type of study: Case-control study
Setting and country: Hospital, US
Funding and conflicts of interest: The paper does not report on funding or conflicts of interest. |
Inclusion criteria: Liveborn infants born during the period 1988–1991 to mothers living in one of 14 NYS counties
N total at baseline: Cases: n=502 Controls: n=1,066
Important prognostic factors2: (Case/Control)
Maternal diabetes (pre-existing); n (%) Yes: 17 (3.4)/9 (0.8) No: 485 (96.6)/1055 (99.0)
Family history of congenital heart defects; n(%) Yes: 51 (10.2)/32 (3.0) No: 448 (89.2)/1021 (95.8)
Maternal caffeine use during periconceptional period; n(%) Ever: 453 (90.2)/912 (85.6) Never: 47 (9.4)/147 (13.8)
Maternal fever during periconceptional period; n(%) Yes:51 (10.2)/64 (6.0) No: 404 (80.5)/927 (87.0)
Trihalomethane exposure during periconceptional period; n(%) High: 92 (18.3)/214 (20.1) Medium: 77 (15.3)/150 (14.1) Low: 88 (17.5)/163 (15.3) None: 161 (32.1)/369 (34.6)
Maternal age at delivery; n(%) 14-19: 16 (3.2)/38 (3.6) 20-34: 411 (81.9)/850 (79.7) 35+: 74 (14.7)/177 (16.6)
Maternal race; n(%) White: 424 (84.5)/870 (81.6) Black: 32 (6.4)/100 (9.4) Other: 46 (9.2)/96 (9.0)
Maternal ethnicity; n(%) Hispanic: 35 (7.0)/70 (6.6) Non-Hispanic: 465 (92.6)/994 (93.3)
Maternal body mass index; n(%) High (>25): 115 (22.9)/198 (18.6) Normal/low:387 (77.1)/868 (81.4)
Infant sex, n(%) Male: 329 (65.5)/579 (54.3) Female: 173 (34.5)/487 (45.7)
|
Describe intervention:
One of 33 British Pediatric Codes for cardiac anomalies that are routinely diagnosed and treated in hospitals prior to the age of 2 were included in the study. All diagnoses must have been confirmed through cardiac catheterization, surgery, or echocardiogram. |
Describe control:
Controls were livebirths without any major birth defects, randomly selected from birth certificates in the 14 study counties and frequency matched by year of birth. Controls were selected in approximately a two to one ratio. |
Length of follow-up: Case-control study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available): Risk of major malformation:
Ventolin use, asthma; n Cases: 15 Controls:14 aOR: 2.37 (0.90, 6.23)
Bronchodilator only, no asthma; n Cases:1 Control: 1 aOR: not calculated
|
The authors conclude that both maternal asthma medication use, particularly bronchodilators, may play a role in cardiac malformations in offspring |
|
Eltonsy, 2011 |
Type of study: Cohort study
Setting and country: Hospital, Canada
Funding and conflicts of interest: funded through grants received from the Fonds de la recherche en sante´ du Quebec, and the Canadian Institutes of Health Research.
One of the authors received funds from AstraZeneca, Amgen, and GlaxoSmithKline |
Inclusion criteria: women between 12-50 years old, who had at least one pregnancy ending in a delivery (live or still birth) between 1990 and 2002, and who were diagnosed with asthma (International Classification of Diseases [ICD]-9 code 493 and used SABA and LABA during the first trimester
N total at baseline: n=13,117
Important prognostic factors2: Users/non-users
SABA Maternal age (years); n(%) <18 535 (7.4)/320 (5.4) 18–34: 6182 (86.1)/5261 (88.6) >35: 465 (6.5) 354 (6.0)
Receipt of social assistance during pregnancy or one year before; n(%) 5873 (81.8)/4537 (76.4)
Urban area of residence at delivery, n(%) 5796 (80.7)/4816 (81.2)
Level of education at delivery (years); n(%) <11: 4313 (60.1)/3465 (58.4) 12–15: 2026/(28.2) 1665 (28.1) >16: 323 (4.5)/347 (5.8) Missing: 520 (7.2)/458 (7.7)
Chronic hypertension; n(%) 183 (2.6)/131 (2.2)
Pregnancy induced hypertension; n(%) 323 (4.5)/265 (4.5)
Diabetes mellitus; n(%) 181 (2.5)/ 123 (2.1)
Gestational diabetes; n(%) 574 (8.0)/441 (7.4)
Epilepsy; n(%) 80 (1.1)/59 (1.0)
Use of teratogenic drugs in first trimester; n(%) 112 (1.6)/57 (1.0)
Uterine complications during pregnancy; n(%) 140 (2.0)/113 (1.9)
Fetal infections during pregnancy; n(%) 56 (0.8)/33 (0.6)
Nullipara; n(%) 2546 (35.7)/1616 (27.3)
Multiple pregnancy; n(%) 100 (1.4) 90/(1.5)
Use of other controller medications in first trimester; n(%) 360 (5.0)/36 (0.6)
Use of intranasal corticosteroids in first trimester; n(%) 375 (5.2)/144 (2.4)
Use of oral corticosteroids in first trimester; n(%) 408 (5.7)/44 (0.7)
Emergency department visit or hospitalization for asthma in first trimester; n(%) 579 (8.1)/76 (1.3)
Exacerbations for asthma in first trimester; n(%) 717 (10.0)/98 (1.7)
Asthma severity in the year before pregnancy, n(%) Mild: 5011 (69.8)/5760 (97.1) Moderate: 1447 (20.2)/163 (2.7) Severe: 724 (10.1)/12 (0.2)
Asthma control in the year before pregnancy; n(%) Controlled: 3093 (43.1)/4900 (82.6) Uncontrolled: 4089 (56.9)/1035 (17.4)
LABA Maternal age (years); n(%) <18: 7 (4.2)/848 (6.6) 18–34: 134 (81.2)/11,309 (87.3) >35: 24 (14.6)/795 (6.1)
Receipt of social assistance during pregnancy or one year before; n(%) 102 (61.8)/10,308 (79.6)
Urban area of residence at delivery, n(%) 130 (78.8)/10,482 (80.9)
Level of education at delivery (years); n(%) <11: 76 (46.1)/7702 (59.5) 12–15: 64 (38.8)/3627 (28.0) >16: 14 (8.5)/656 (5.1) Missing: 11 (6.7)/967 (7.5)
Chronic hypertension; n(%) 9 (5.5)/305 (2.4)
Pregnancy induced hypertension; n(%) 8 (4.9)/580 (4.5)
Diabetes mellitus; n(%) 12 (7.3)/292 (2.3)
Gestational diabetes; n(%) 28 (17.0)/987 (7.6)
Epilepsy; n(%) 4 (2.4)/135 (1.0)
Use of teratogenic drugs in first trimester; n(%) 5 (3.0)/164 (1.3)
Uterine complications during pregnancy; n(%) 4 (2.4)/249 (1.9)
Fetal infections during pregnancy; n(%) 4 (2.4)/85 (0.7)
Nullipara; n(%) 67 (40.6)/4095 (31.8)
Multiple pregnancy; n(%) 2 (1.2)/188 (1.5)
Use of other controller medications in first trimester; n(%) 22 (13.3)/374 (2.9)
Use of intranasal corticosteroids in first trimester; n(%) 25 (15.2)/494 (3.8)
Use of oral corticosteroids in first trimester; n(%) 31 (18.8)/421 (3.3)
Emergency department visit or hospitalization for asthma in first trimester; n(%) 22 (13.3)/633 (4.9)
Exacerbations for asthma in first trimester; n(%) 31 (18.8)/784 (6.1)
Asthma severity in the year before pregnancy, n(%) Mild: 48 (29.1)/10,723 (82.8) Moderate: 47 (28.5)/1563 (12.1) Severe: 70 (42.4)/666 (5.1)
Asthma control in the year before pregnancy; n(%) Controlled: 35 (21.2)/7958 (61.4) Uncontrolled: 130 (78.8)/4994 (38.6) |
Describe intervention:
Exposure to SABA and LABA during the first trimester
|
Describe control:
No exposure to SABA and LABA during the first trimester
|
Length of follow-up: Cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
Risk of major malformation: SABA use in first trimester; n(%) Yes: 691 (9.6) No: 551 (9.3) aOR: 1.04 (0.92–1.17)
LABA use in first trimester; n(%) Yes: 21 (12.7) No: 1221 (9.4) aOR: 1.37 (0.92–2.17)
|
The authors conclude that results are in concordance with asthma management guidelines, to the safety of SABA use during pregnancy even at doses as high as 10 per week. |
|
Kallen, 2007 |
Type of study: Cohort study
Setting and country: Hospital, Sweden
Funding and conflicts of interest: The paper does not report on funding or conflicts of interest. |
Inclusion criteria: women who reported the use of anti-asthmatic drugs in early pregnancy and women who were prescribed anti-asthmatic drugs later during pregnancy.
N total at baseline: Early exposure: n=24,369 Late exposure: n=7,778 Controls without asthma: n=860,215
Important prognostic factors2: Early uses/ late use/population
Maternal age; n <20: 733/150/16,282 20-24: 4,371/1,154/123,797 25-29: 8,366/2,646/290,067 30-34: 7,357/2,443/286,067 35-39: 2,994/1,175/121,669 40-44: 520/205/21,493 >45: 20/5/840
Parity, n 1: 12,088/3,451/373,859 2: 7,560/2,527/309,868 3: 3,176/1,196/121,213 >4: 1,545/604/55,275
Smoking, n Unknown: 672/228/55,958 No: 19,837/6,459/704,918 <10 cigarettes/day: 2,535/721/67,484 >10 cigarettes/day:1,325/370/31,855 any smoking: 3,860/1,091/99,339
Previous miscarriages, n None: 19,054/5,999/693,178 1: 4,014/1,323/128,484 2: 900/315/27,865 ≥3: 401/141/10,688
BMI, n Unknown: 2,862/735/132,003 <19.8: 1,601/572/64,624 19.8–25.9:12,165/3,929/471,606 26–29.9: 4,208/1,353/12,0764 ≥30: 3,535/1,189/71,252
Years of subfertility, n None: 22,458/7,046/803,037 1: 459/186/15,106 2: 581/213/16,681 3: 326/124/9,160 4: 164/76/5,363 ≥5: 381/133/10,868 |
Describe intervention:
Pregnant women who reported the use of anti-asthmatic drugs in early pregnancy and women who were prescribed anti-asthmatic drugs later during pregnancy. |
Describe control:
Pregnant women without asthma
|
Length of follow-up: Cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
All malformations; OR (95% CI) Salbutamol: 1.09 (0.97–1.75) Terbutaline: 1..11 (1.04–1.19)
Any cardiac defect Salbutamol: 1.38 (1.12–1.70) Terbutaline: (1.08 0.94–1.23)
|
The authors conclude that an increased risk for congenital malformation appears to exist among infants born to women who used anti-asthmatic drugs in early pregnancy. The risk increase is small and it is unclear if it is due to the asthma disease, to residual confounding, or to drugs used.
|
|
Tata, 2008 |
Type of study: Case-control study
Setting and country: Hospital, UK
Funding and conflicts of interest: funded through grants received from Asthma UK
No conflicts of interest. |
Inclusion criteria: women of childbearing age (15–50 years) who gave birth to liveborn children with one or more major malformation between January 1988 and November 2004
Controls were liveborn children matched by year of birth, general practice and singleton or twin delivery without major malformation.
N total at baseline: Cases: n=5124 Controls: n=30,053
Important prognostic factors2: Cases/controls
Median maternal age at delivery; years 29.6/29.4
Maternal BMI, n(%) <18.5: 163 (3.2)/827 (2.8) 18.5-24.9: 2031 (39.6)/12280 (40.9) 25-29.9: 709 (13.8)/4131 (13.7) >30: 385 (7.5)/1997 (6.6) Missing: 1836 (35.8)/10818 (36.0)
Maternal smoking status; n(%) Non-smoker: 2590 (50.5)/15046 (50.1) Ex-smoker: 269 (5.2)/1473 (4.9) Current smoker: 1136/(22.2) 6637 (22.1) Missing: 1129 (22.0)/6897 (23.0)
Household Townsend score quintile, n(%) 1: 826 (16.1)/4976 (16.6) 2: 592 (11.6)/3499 (11.6) 3: 586 (11.4)/3387 (11.3) 4: 506 (9.9)/2833 (9.4) 5: 400 (7.8)/2337 (7.8) Missing: 2214 (43.2)/13021 (43.3) Term of pregnancy, n(%) Preterm: 366 (7.1)/858 (2.9) Term: 705 (13.8)/4503 (15.0) Post-term: 8 (<0.5)/39 (<0.5) Missing: 4045 (78.9)/24653 (82.1) Sex of child, n(%) Female: 2172 (42.4)/14829 (49.4) Male: 2952 (57.6)/15224 (50.7) Singleton or multiple delivery, n(%) Singleton: 4996 (97.5)/29655 (98.7) Twin: 128 (2.5)/398 (1.3)
Year of birth, n(%) 1988–9: 196 (3.8)/1104 (3.7) 1990–4: 1567 (30.6)/9192 (30.6) 1995–9: 1768 (34.5)/10389 (34.6) 2000–4: 1593 (31.1)/9368 (31.2) |
Describe intervention:
Children born with major malformation |
Describe control:
Control children born without major malformation |
Length of follow-up: Cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
Risk of major malformations Any asthma medication; OR (95% CI) 1.05 (0.94 to 1.18)
Short-acting β agonist; OR (95% CI) 1.06 (0.94 to 1.19)
Inhaled corticosteroid; OR (95% CI) 1.07 (0.92 to 1.24)
Long-acting β agonist; OR (95% CI) 1.12 (0.72 to 1.75)
Oral corticosteroid; OR (95% CI) 1.23 (0.89 to 1.69) |
The authors conclude that an increased risk for congenital malformation appears to exist among infants born to women who used anti-asthmatic drugs in early pregnancy. The risk increase is small and it is unclear if it is due to the asthma disease, to residual confounding, or to drugs used.
|
|
Bracken, 2003 |
Type of study: Cohort study
Setting and country: Hospital, US
Funding and conflicts of interest: funded through grants received from the National Institutes of Health
No conflicts of interest. |
Inclusion criteria: Women with a history of physician-diagnosed asthma and women nonasthmatics matched by geographic region to asthmatic subjects.
Controls were liveborn children matched by year of birth, general practice and singleton or twin delivery without major malformation.
N total at baseline: N=2206 Asthmatic: n=873 Non-asthmatic: n=1333
Important prognostic factors2: Respondent’s age (years); n(%) <24: 566 (25.7) 25–29: 576 (26.1) 30–34: 689 (31.2) >35: 374 (17.0)
Previous pregnancies; n(%) 0: 653 (29.6) 1: 670 (30.4) 2: 450 (20.4) >3: 428 (19.4)
Number of prior live births; n(%) 0: 996 (45.2) 1: 750 (34.0) 2: 339 (15.4) >3: 121 (54.9)
Marital status; n(%) Currently married: 1511 (63.0) Never married: 610 (27.7) Previously married: 83 (37.6)
Race; n(%) White: 1496 (67.9) Black: 209 (9.5) Hispanic: 406 (18.4) Other: 89 (4.0)
Education; n(%) <high school: 324 (14.7) High school graduate: 387 (17.5) Some college: 533 (24.2) College graduate: 510 (23.2) >College: 449 (20.4)
Prepregnancy weight (lb); n(%) <120: 397 (18.0) 120–139: 684 (31.0) 140–159: 455 (20.6) >160: 634 (28.7)
Height (in); n(%) <63 620 (28.1) 63–64: 576 (26.1) 65–66: 482 (21.9) >67: 514 (23.3)
Smoking, 1st trimester (average cigarettes per day); n(%) 0: 1829 (82.9) <10: 302 (13.7) >10: 74 (3.4)
Smoking, 3rd trimester (average cigarettes per day); n(%) 0: 1780 (80.7) <10: 106 (85.5) >10: 34 (87.0)
Caffeine, 1st trimester (mg/d); n(%) 0: 920 (41.7) 1–149: 1163 (52.7) 150–299: 97 (4.4) >300: 25 (1.1)
Prenatal vitamin use, 1st Trimester; n(%) None: 314 (14.2) 1 mo: 403 (18.3) 2 mo: 748 (33.9) >3 mo: 742 (33.6) |
Describe intervention
Asthma severity and exposure to asthma medication, |
Describe control:
No exposure to astma medication, no asthma. |
Length of follow-up: Cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
Pre-term delivery Short-acting bronchodilator use; aOR (95% CI) 1.14 (0.79 to 1.66)
Long-acting bronchodilator use; aOR (95%CI) 1.69 (0.76 to 3.77)
Leukotriene inhibitor use; aOR (95%CI) 3.90 (0.80 to 18.92)
Oral steroid use; aOR (95%CI) 3.37 (1.66 to 6.86)
Inhaled steroid use; aOR (95%CI) 1.29 (0.74 to 2.25)
Low Birth Weight Short-acting bronchodilator use; aOR (95% CI) 0.97 (0.65 to 1.47)
Long-acting bronchodilator use; aOR (95%CI) 1.10 (0.39 to 3.11)
Leukotriene inhibitor use; aOR (95%CI) 2.43 (0.28 to 20.91
Oral steroid use; aOR (95%CI) 1.01 (0.24 to 4.31)
Inhaled steroid use; aOR (95%CI) 0.74 (0.36 to 1.55) |
The authors conclude that no effect of asthma symptoms or severity on preterm delivery but observed increased risks associated with use of oral steroid. Moreover, the authors conclude that women with asthma symptoms but no diagnosis were at particular risk of undermedication and delivering IUGR infants.
|
|
Bakhireva, 2005 |
Type of study: Cohort study
Setting and country: Hospital, US
Funding and conflicts of interest: The paper does not report on funding.
One of the reviewers reported receiving grants/research support from GlaxoSmithKline and serving on the speakers’ bureau for AstraZeneca and Merck. |
Inclusion criteria: pregnant women across North America with a current diagnosis of asthma, regardless of medications used or frequency of treatment.
Pregnant women who did not have asthma were recruited as a Non-diseased comparison group.
N total at baseline: N=957 Controls: n=303 β2-Agonists only: n=103 Inhaled Steroids: n=438 Systemic steroids: n=113
Important prognostic factors2: Maternal age; n(%) <25: 94 (9.8) 35+: 268 (28.0)
BMI (kg/m2); n(%) <24: 512 (53.5) >28: 207 (21.6)
Gravidity > 1; n(%) 618 (64.6)
Parity > 0; n(%) 467 (48.8)
White non-Hispanic; n(%) 845 (88.3)
Any tobacco use; n(%) 89 9.4
Any alcohol use; n(%) 435 47.3
Gestational diabetes; n(%) 34 (3.6)
SES status above average; n(%) 698 (74.2)
Gestational age <37 wk; n(%) 80 (8.4)
Major structural anomalies; n(%) 26 (2.7)
Pre-eclampsia/PIH; n(%) 26 (2.8)
Gestational age at delivery, wk; Mean (SD) 39.2 (1.7)
Maternal weight gain, kg; mean (SD) 15.8 (6.9) |
Describe intervention:
Pregnant women with asthma
|
Describe control:
Pregnant women who do not have asthma |
Length of follow-up: cohort study; no follow-up
Loss-to-follow-up; n (%): Not applicable
Incomplete outcome data: No incomplete data
|
Outcome measures and effect size (include 95%CI and p-value if available):
Low birth weight β2-Agonists vs controls; aOR (95%CI) 0.57 (0.16-2.12)
Inhaled steroids vs controls; aOR (95%CI) 1.55 (0.77-3.10)
Systemic steroids vs controls; aOR (95%CI) 1.82 (0.65-5.08) |
The authors conclude that The treatment of asthma with systemic corticosteroids resulted in a deficit of about 200 g in birth weight compared with controls and exclusive b2-agonist users and no increased incidence of SGA. These results suggest that asthma management with b2-agonists and/or inhaled corticosteroids during pregnancy does not impair fetal growth, whereas systemic corticosteroids have a minimal effect |
|
Namazy, 2020 |
Type of study: Cohort study
Setting and country: Hospital, US
Funding and conflicts of interest: Authors received funding from Genetech. |
Inclusion criteria: Asthmatic women were eligible to enroll in the EXPECT cohort if they were currently pregnant and received 1 or more doses of omalizumab at any time during pregnancy or during the 8 weeks before conception (a window selected to reflect omalizumab’s half-life of 26 days)
N total at baseline: EXPECT cohort: n=230 QECC cohort: n=1153
Important prognostic factors2: Expect/QECC
Age (year); Median (range) 30.0 (16-45)/27.7 (15.3-44.6)
Obesity; % 46.7%/ NA
Smoking;% 7.4%/NA
Asthma medications during pregnancy ICSs 81.3%/100.0% Leukotriene receptor antagonists: 49.6%/7.8% Oral corticosteroids: 23.7%/22.8%
|
Describe intervention: Pregnant women with asthma who received 1 or more doses of omalizumab at any time during pregnancy or during the 8 weeks before conception |
Describe control: A disease-matched external comparator cohort (QECC) unexposed to omalizumab |
Length of follow-up: Up to 18 months after birth
Loss-to-follow-up; n (%): Not described
Incomplete outcome data: Not described, unclear how in complete data was handled
|
Outcome measures and effect size (include 95%CI and p-value if available):
Infants with a major congenital anomaly EXPECT 8.1% (18/223 [4.9% to 12.5%])
QECC 8.9% (102/1124 [7.0% to 10.8%])
Low birth weight EXPECT 13.7% (9.5% to 18.9%)
QECC 9.8% (7.9% to 11.8%)
Small for gestational age EXPECT 9.7% (6.2% to 14.4%)
QECC 15.8% (13.3% to 18.4%)
Premature birth EXPECT 15.0% (10.7% to 20.3%)
QECC 11.3% (9.2% to 13.5%) |
The authors conclude that there was no evidence of an increased risk of major congenital anomalies among pregnant women exposed to omalizumab compared with a disease-matched unexposed cohort. |
|
Namazy, 2015 |
Type of study: Cohort study
Setting and country: Hospital, US
Funding and conflicts of interest: Authors received funding from Genetech. |
Inclusion criteria: Asthmatic women were eligible to enroll in the EXPECT cohort if they were currently pregnant and received 1 or more doses of omalizumab at any time during pregnancy or during the 8 weeks before conception (a window selected to reflect omalizumab’s half-life of 26 days)
N total at baseline: EXPECT cohort: n=230 QECC cohort: n=1153
Important prognostic factors2: Expect/QECC
Age (year); Median (range) 30.0 (16-45)/27.7 (15.3-44.6)
Obesity; % 46.7%/ NA
Smoking;% 7.4%/NA
Asthma medications during pregnancy ICSs 81.3%/100.0% Leukotriene receptor antagonists: 49.6%/7.8% Oral corticosteroids: 23.7%/22.8% |
Describe intervention: Pregnant women with asthma who received 1 or more doses of omalizumab at any time during pregnancy or during the 8 weeks before conception |
Describe control: No control group included |
Length of follow-up: Up to 18 months after birth
Loss-to-follow-up; n (%): Not described
Incomplete outcome data: Not described, unclear how in complete data was handled
|
Outcome measures and effect size (include 95%CI and p-value if available):
Infants with a major congenital anomaly; % (95%CI) 4.4 (1.8-8.8)
Low birth weight;% (95%CI) 3.2 (0.9-8.0)
Small for gestational age; % (95%CI) 10.9 (6.4-17.1)
Premature birth; % (95%CI) 14.5 (9.3-21.1)
Stillbirth;% (95%CI) 0.60 (0-3.3)
Spontaneous abortion;% (95%CI) 8.6 (4.4-14.9) |
The authors conclude that proportions of major congenital anomalies, prematurity, low birth weight, and small size for gestational age observed in the EXPECT registry are not inconsistent with findings from other studies in this asthma population |
Notes:
- Prognostic balance between treatment groups is usually guaranteed in randomized studies, but non-randomized (observational) studies require matching of patients between treatment groups (case-control studies) or multivariate adjustment for prognostic factors (confounders) (cohort studies); the evidence table should contain sufficient details on these procedures
- Provide data per treatment group on the most important prognostic factors [(potential) confounders]
- For case-control studies, provide sufficient detail on the procedure used to match cases and controls
- For cohort studies, provide sufficient detail on the (multivariate) analyses used to adjust for (potential) confounders
Risk of bias tables
1. Risk of bias table for intervention studies (observational: non-randomized clinical trials, cohort and case-control studies)
|
Study reference
(first author, year of publication) |
Bias due to a non-representative or ill-defined sample of patients?1
(unlikely/likely/unclear) |
Bias due to insufficiently long, or incomplete follow-up, or differences in follow-up between treatment groups?2
(unlikely/likely/unclear)
|
Bias due to ill-defined or inadequately measured outcome ?3
(unlikely/likely/unclear) |
Bias due to inadequate adjustment for all important prognostic factors?4
(unlikely/likely/unclear) |
|
Vasilikas-Scaramoza, 2013 |
Unlikely |
Unlikely |
Unlikely |
Likely |
|
Garne, 2016; |
Unlikely |
Unclear |
Unlikely |
Likely |
|
Lin, 2009; |
Unlikely |
Unclear |
Unlikely |
Unlikely |
|
Eltonsy, 2011; |
Unlikely |
Unclear |
Unclear |
Unlikely |
|
Kallen 2007; |
Unlikely |
Unclear |
Unlikely |
Unlikely |
|
Tata, 2008; |
Unlikely |
Unclear |
Unlikely |
Unlikely |
|
Bracken, 2003 |
Unlikely |
Unlikely |
Unlikely |
Unlikely |
|
Blais 2007; |
Unlikely |
Unclear |
Unlikely |
Unlikely |
|
Bakhireva, 2005 |
Unlikely |
Unlikely |
Unlikely |
Unlikely |
|
Cavero-Carbonell, 2017 |
Unlikely |
Unclear |
Unlikely |
Unlikely |
|
Namazy, 2015; |
Unlikely |
Unlikely |
Unlikely |
Unclear |
|
Namazy, 2020 |
Unlikely |
Unlikely |
Unlikely |
Unlikely |
- Failure to develop and apply appropriate eligibility criteria: a) case-control study: under- or over-matching in case-control studies; b) cohort study: selection of exposed and unexposed from different populations.
- Bias is likely if: the percentage of patients lost to follow-up is large; or differs between treatment groups; or the reasons for loss to follow-up differ between treatment groups; or length of follow-up differs between treatment groups or is too short. The risk of bias is unclear if: the number of patients lost to follow-up; or the reasons why, are not reported.
- Flawed measurement, or differences in measurement of outcome in treatment and control group; bias may also result from a lack of blinding of those assessing outcomes (detection or information bias). If a study has hard (objective) outcome measures, like death, blinding of outcome assessment is not necessary. If a study has “soft” (subjective) outcome measures, like the assessment of an X-ray, blinding of outcome assessment is necessary.
- Failure to adequately measure all known prognostic factors and/or failure to adequately adjust for these factors in multivariate statistical analysis.
2. Table of quality assessment for systematic reviews of RCTs and observational studies
|
Study
First author, year |
Appropriate and clearly focused question?1
Yes/no/unclear |
Comprehensive and systematic literature search?2
Yes/no/unclear |
Description of included and excluded studies?3
Yes/no/unclear |
Description of relevant characteristics of included studies?4
Yes/no/unclear |
Appropriate adjustment for potential confounders in observational studies?5
Yes/no/unclear/not applicable |
Assessment of scientific quality of included studies?6
Yes/no/unclear |
Enough similarities between studies to make combining them reasonable?7
Yes/no/unclear |
Potential risk of publication bias taken into account?8
Yes/no/unclear |
Potential conflicts of interest reported?9
Yes/no/unclear |
|
Namazy, 2013 |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
No |
Unclear1 |
|
Rahimi, 2016 |
Yes |
Yes |
Yes |
No |
Yes |
No |
Yes |
No |
No |
|
Murphy, 2013 |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
1 conflicts of interests are not reported for the individual studies.
- Research question (PICO) and inclusion criteria should be appropriate and predefined
- Search period and strategy should be described; at least Medline searched; for pharmacological questions at least Medline + EMBASE searched
- Potentially relevant studies that are excluded at final selection (after reading the full text) should be referenced with reasons
- Characteristics of individual studies relevant to research question (PICO), including potential confounders, should be reported
- Results should be adequately controlled for potential confounders by multivariate analysis (not applicable for RCTs)
- Quality of individual studies should be assessed using a quality scoring tool or checklist (Jadad score, Newcastle-Ottawa scale, risk of bias table etc.)
- Clinical and statistical heterogeneity should be assessed; clinical: enough similarities in patient characteristics, intervention and definition of outcome measure to allow pooling? For pooled data: assessment of statistical heterogeneity using appropriate statistical tests (e.g. Chi-square, I2)?
- An assessment of publication bias should include a combination of graphical aids (e.g., funnel plot, other available tests) and/or statistical tests (e.g., Egger regression test, Hedges-Olken). Note: If no test values or funnel plot included, score “no”. Score “yes” if mentions that publication bias could not be assessed because there were fewer than 10 included studies.
- Sources of support (including commercial co-authorship) should be reported in both the systematic review and the included studies. Note: To get a “yes,” source of funding or support must be indicated for the systematic review AND for each of the included studies.
Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 12-04-2023
Laatst geautoriseerd : 12-04-2023
Geplande herbeoordeling :
Algemene gegevens
De ontwikkeling van deze richtlijn werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS). Patiëntenparticipatie bij deze richtlijn werd medegefinancierd uit de Kwaliteitsgelden Patiënten Consumenten (SKPC) binnen het programma KIDZ. De financiers hebben geen enkele invloed gehad op de inhoud van de richtlijn.
Samenstelling werkgroep
Voor het ontwikkelen van de richtlijnmodule is in 2019 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor zwangere vrouwen met astma.
Belangenverklaringen
De Code ter voorkoming van oneigenlijke beïnvloeding door belangenverstrengeling is gevolgd. Alle werkgroepleden hebben schriftelijk verklaard of zij in de laatste drie jaar directe financiële belangen (betrekking bij een commercieel bedrijf, persoonlijke financiële belangen, onderzoeksfinanciering) of indirecte belangen (persoonlijke relaties, reputatiemanagement) hebben gehad. Gedurende de ontwikkeling of herziening van een module worden wijzigingen in belangen aan de voorzitter doorgegeven. De belangenverklaring wordt opnieuw bevestigd tijdens de commentaarfase.
Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten.
|
Werkgroeplid |
Functie |
Nevenfuncties |
Gemelde belangen |
Ondernomen actie |
|
Nederveen-Bendien* |
longarts |
werkgroeplid NHG standaard astma, betaald |
Betaald: scholing gegeven voor huisartsen, LVPK en specialisten voor ALK, GSK, Sanofi en AstraZeneca |
Geen betaald adviseurschap gedurende de periode van de richtlijn ontwikkeling |
|
Feitsma |
gynaecoloog |
bestuurslid Integrale Geboortezorgorganisatie HJGC (IGO HJGC), onbetaald |
Geen |
Geen |
|
Koehorst-ter Huurne |
beherend apotheker |
lid special interest group (SIG) Long, KNMP |
Geen |
Geen |
|
Brons |
ervaringsdeskundige Longfonds |
Docent-onderzoeker, lid Cliëntenraad Merem (vrijwilligersvergoeding), |
Geen |
Geen |
|
Wittkampf |
longverpleegkundige |
Voorzitter V&VN longverpleegkundigen, onbetaald |
Geen |
Geen |
|
Kuiterman |
zelfstandig waarnemend verloskundige 1e lijn
|
Geen |
Geen |
Geen |
|
Van der Meer |
longarts
|
Geen |
Adviesraad Chiesi: triple therapie bij astma, betaald Unrestricted research grant MD-PhD traject: GlaxoSmithKline, Teva Stichtijng Longziekten Fryslan Medical Centre Leeuwarden research fund |
Geen |
|
De Kruif |
longarts |
Geen |
Geen |
Geen |
|
Hoolwerff |
kaderarts astma/COPD |
Werkzaam als huisarts, betaald. |
Geen |
Geen |
|
Poulissen |
sr. projectleider zorg |
Geen |
Geen |
Geen |
*voorzitter richtlijncommissie
Inbreng patiëntenperspectief
Er werd aandacht besteed aan het patiëntenperspectief door het organiseren van een focusgroep en het invullen van een patietenvragenlijst (ontworpen speciaal voor deze richtlijn m.b.v. de dialoogtool van PGO support), afvaardiging van patiëntenvereniging in de werkgroep en betrekken van patiëntenvertegenwoordigers bij het ontwikkelen van Thuisarts-situaties. Het verslag hiervan van de focusgroep (zie aanverwante producten) is besproken in de werkgroep. De verkregen input is meegenomen bij het opstellen van de overwegingen (zie kop ‘waarden en voorkeuren van patiënten’ bij module ‘Monitoring’). De conceptrichtlijn is tevens voor commentaar voorgelegd aan de patiëntenvereniging en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.
Wkkgz & Kwalitatieve raming van mogelijke substantiële financiële gevolgen
Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz
Bij de richtlijn is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling zijn richtlijnmodules op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).
Uit de kwalitatieve raming blijkt dat er waarschijnlijk geen substantiële financiële gevolgen zijn (zie onderstaande tabel).
Module |
Uitkomst raming |
Toelichting |
|
Module 1a Veiligheid van astmamedicatie |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
|
Module 1b Step-down in inhalatiemedicatie |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
|
Module 1c ICS-formoterol ‘zo nodig’ therapie |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
|
Module 2 Astmamedicatie tijdens borstvoeding |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
|
Module 3a Neonatale uitkomsten |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
|
Module 3b Voorspellers van negatieve uitkomsten |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
|
Module 4 Preceonceptioneel advies |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
|
Module 5 Monitoring van astma bij zwnageren |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
|
Module 6 Organisatie van zorg |
geen financiële gevolgen |
Hoewel uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat [het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet OF het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft]. Er worden daarom geen financiële gevolgen verwacht. |
Werkwijze
AGREE
Deze richtlijn is opgesteld conform de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).
Knelpuntenanalyse en uitgangsvragen
Tijdens de voorbereidende fase inventariseerde de werkgroep de knelpunten in de zorg voor zwangere vrouwen met astma door middel van een schriftelijke knelpunteninventarisatie (enquête). De volgende partijen zijn gevraagd om knelpunten aan te dragen: Inspectie Gezondheidszorg en Jeugd (IGJ), Lareb, Nederlandse Associatie Physician Assistants (NAPA), Nederlandse Vereniging van Longfunctieanalisten (NVLA), Nederlandse zorgautoriteit (NZA), Nederlandse Federatie van Universitair Medische Centra (NFU), Nederlandse Vereniging van Ziekenhuizen (NVZ), Patiëntenfederatie Nederland, Samenwerkende Topklinische opleidingsZiekenhuizen (STZ), Vereniging Innovatieve Geneesmiddelen (VIG), Zorginstituut Nederland (ZiNL), Zelfstandige Klinieken Nederland (ZKN), Zorgverzekeraars Nederland (ZN), Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie (KNMP), Koninklijke Nederlandse Organisatie van Verloskundigen (KNOV), Longfonds, Nederlands Huisartsen Genootschap (NHG), Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT), Nederlandse Vereniging voor Obstetrie & Gynaecologie (NVOG), Verpleegkundigen & Verzorgenden Nederland (V&VN). Het verslag van de schriftelijke knelpunteninventarisatie is opgenomen onder aanverwante producten. Op basis van de uitkomsten van de knelpuntenanalyse zijn door de werkgroep concept-uitgangsvragen opgesteld en definitief vastgesteld.
Uitkomstmaten
Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde de werkgroep welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. De werkgroep waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Tevens definieerde de werkgroep tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.
Methode literatuursamenvatting
Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder ‘Zoeken en selecteren’ onder Onderbouwing. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. Review Manager 5.4 werd gebruikt voor de statistische analyses. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.
Beoordelen van de kracht van het wetenschappelijke bewijs
De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (zie http://www.gradeworkinggroup.org/). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding).
GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).
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Definitie |
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Hoog |
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Redelijk |
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Laag |
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Zeer laag |
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Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in richtlijnen volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet één op één vergelijkbaar met het minimaal klinisch relevant verschil (Minimal Clinically Important Difference, MCID). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming met betrekking tot de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).
Overwegingen (van bewijs naar aanbeveling)
Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje ‘Overwegingen’ en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision framework is een integraal onderdeel van de GRADE methodiek.
Formuleren van aanbevelingen
De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. De kracht van het wetenschappelijk bewijs en het gewicht dat door de werkgroep wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Conform de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. De werkgroep heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.
In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.
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Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers |
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Sterke aanbeveling |
Zwakke (conditionele) aanbeveling |
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Voor patiënten |
De meeste patiënten zouden de aanbevolen interventie of aanpak kiezen en slechts een klein aantal niet. |
Een aanzienlijk deel van de patiënten zouden de aanbevolen interventie of aanpak kiezen, maar veel patiënten ook niet. |
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Voor behandelaars |
De meeste patiënten zouden de aanbevolen interventie of aanpak moeten ontvangen. |
Er zijn meerdere geschikte interventies of aanpakken. De patiënt moet worden ondersteund bij de keuze voor de interventie of aanpak die het beste aansluit bij zijn of haar waarden en voorkeuren. |
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Voor beleidsmakers |
De aanbevolen interventie of aanpak kan worden gezien als standaardbeleid. |
Beleidsbepaling vereist uitvoerige discussie met betrokkenheid van veel stakeholders. Er is een grotere kans op lokale beleidsverschillen. |
Organisatie van zorg
In de knelpuntenanalyse en bij de ontwikkeling van de richtlijn is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, mankracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in de module Organisatie van zorg.
Commentaar- en autorisatiefase
De conceptrichtlijnmodule werd aan de betrokken (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd ter commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijnmodule aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijnmodule werd aan de deelnemende (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd voor autorisatie en door hen geautoriseerd dan wel geaccordeerd.
Literatuur
Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey. BMJ Open. 2017 Nov 16;7(11):e018593. doi: 10.1136/bmjopen-2017-018593. PubMed PMID: 29150475; PubMed Central PMCID: PMC5701989.
Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016 Jun 28;353:i2016. doi: 10.1136/bmj.i2016. PubMed PMID: 27353417.
Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089. doi: 10.1136/bmj.i2089. PubMed PMID: 27365494.
Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010 Dec 14;182(18):E839-42. doi: 10.1503/cmaj.090449. Epub 2010 Jul 5. Review. PubMed PMID: 20603348; PubMed Central PMCID: PMC3001530.
Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13. doi: 10.1016/j.jclinepi.2017.05.006. Epub 2017 May 18. PubMed PMID: 28529184; PubMed Central PMCID: PMC6542664.
Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwaliteit.
Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.
Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.
Zoekverantwoording
Zoekacties zijn opvraagbaar. Neem hiervoor contact op met de Richtlijnendatabase.