Dreigende vroeggeboorte

Initiatief: NVOG Aantal modules: 15

Corticosteroiden bij geplande sectio tussen 34+0 en 36+6 weken zwangerschapsduur

Uitgangsvraag

Wat zijn de gewenste en ongewenste effecten op maternale, perinatale en lange-termijnuitkomsten van het toedienen van antenatale corticosteroiden bij zwangere vrouwen die tussen 34+0 en 36+6 weken zwangerschapsduur een electieve sectio ondergaan, vergeleken met placebo of geen interventie?

Aanbeveling

Voor het uitvoeren van een keizersnede vóór 39+0 weken zwangerschapsduur moet een duidelijke indicatie bestaan.

 

Overweeg het gebruik van antenatale corticosteroiden bij zwangere vrouwen die tussen 34+0 en 34+6 weken zwangerschapsduur een sectio ondergaan om de incidentie van neonataal respiratoir distress syndroom (RDS) te verminderen.

Houd daarbij voor ogen dat met toenemende zwangerschapsduur de risico’s van corticosteroiden ten opzichte van de gunstige effecten toenemen.

 

Bespreek de afweging tussen risico’s en gunstige effecten van antenatale corticosteroiden met zwangere vrouwen die tussen 35+0 en 36+6 weken zwangerschapsduur een electieve sectio ondergaan.

Overwegingen

Pros and cons of the intervention and quality of the evidence

The results of the literature analysis are inconclusive for the crucial outcomes.

 

Adverse effects/complications

Although the administration of maternal corticosteroids may decrease RDS and admission to neonatal special care in neonates born after planned caesarean birth from 37+0 to 39+6 weeks of gestation, it may result in harm to the neonate.

  • Neonatal hypoglycaemia. Extrapolating from a study investigating the administration of corticosteroid to woman at risk of later preterm birth, it seems likely that steroids increase neonatal hypoglycaemia (RR 1.60 (1.37 to 1.87)) (Gyamfi-Bannerman, 2016). A retrospective cohort study including 99 neonates whose mother had received antenatal corticosteroids, found that the occurrence of neonatal hypoglycaemia was independent from the time interval between steroid administration and birth (di Pasquo, 2020). Neonatal hypoglycaemia has also been demonstrated in women with diabetes who have received steroids prior to caesarean birth at term (Gupta, 2020). The long-term metabolic and neurological consequences of neonatal hypoglycaemia are uncertain; a follow-up cohort (at 4.5 years) from the Children With Hypoglycemia and Their Later Development (CHYLD) Study found that neonatal hypoglycaemia was associated with a dose-dependent increased risk of poor executive function and visual motor function and may therefore impact on later learning (McKinlay, 2017).
  • Educational attainment. The administration of corticosteroids may reduce educational attainment at school age (increase in the proportion of children ranked by teachers as being in lower quartile of academic ability from 9% to 18%; and reduction in proportion of children obtaining English proficiency from 13% to 7%) (Stutchfield, 2013).
  • Behavioural disorders. A retrospective population-based study from Finland that included 670097 children found that exposure to maternal antenatal corticosteroid treatment, compared with nonexposure, was significantly associated with mental and behavioural disorders in children (HR [95% CI] 1.33 [1.26 to 1.41]) (Raikkonen, 2020).  In a cohort of one hundred and seventy nine surviving adults 29–36 years old, who were born at extremely low birthweight (<1kg), exposure to antenatal corticosteroid was associated with clinically significant anxiety (OR 3.34 [95% CI 1.03 to 10.81) (Savoy, 2016) .
  • Birthweight. A retrospective population-based study from Finland that included 278508 children found that exposure to maternal antenatal corticosteroid treatment, compared with nonexposure, was significantly associated with reduction in birth size in both preterm and term born infants (Rodriguez, 2019). An individual participant data meta-analysis of 11 trials of multiple doses of antenatal corticosteroids (4857 women and 5915 infants) found that birthweight was lower in the repeat corticosteroid group than the control group (mean difference in z score of -0.12, 95%CI -0.18 to -0.06, 5902 infants, 11 trials, p=0.80 for heterogeneity) (Crowther, 2019).
  • Biological plausibility of effects. Animal studies have shown dose dependent effects on neurodevelopment, behaviour, Hypothalamic Pituitary Axis function, and birthweight, adding to the biological plausibility of effects described above (reviewed in Kemp, 2018).

 

Table

Summary of evidence on harms and benefits of antenatal corticosteroids from 34+0 weeks onwards to inform discussions with parents

 

Benefits

Harms

Uncertainties

34+0 to 34+6 weeks

 

Highly likely to reduce 

- perinatal mortality (156 per 1000 to 133 per 1000 average RR 0.85 [0.77 to 0.93]), 

- neonatal death (119 per 1000 to 93 per 1000 births average RR 0.78 [0.70 to 0.87])

- neonatal respiratory distress (148 per 1000 to 105 per 1000 births; average RR 0.71 [0.65 to 0.78])

 

Likely to reduce

intraventricular haemorrhage (33 per 1000 to 19 per 1000 average RR 0.58 [0.45 to 0.75]). 1 NB Figures include women <34+0 weeks’ gestation.

-------------------------------

Reductions in the above conditions are most likely to be seen if birth is 24- 48 hours after starting treatment. 2 NB Figures include women <34+0 weeks’ gestation.

 

A reduction in respiratory morbidity (but not mortality or interventricular haemorrhage) likely to be seen if birth is within 7 days of starting treatment. 2 NB Figures include women <34+0 weeks’ gestation.

Likely to affect maternal glucose tolerance (with higher risk in diabetic women). 6

 

Likely to reduce birthweight if birth >7 days after steroids (MD -147.01 g, 95% CI -291.97 to -2.05). 2 NB Figures include women <34+0 weeks’ gestation.

 

No benefits are likely to be seen if birth is > 7 days after starting treatment. 2 NB Figures include women <34+0 weeks’ gestation.

 

Likely to increase mental and behavioural  disorders in children (HR [95% CI 1.33 [1.26; 1.41]) 7

 

 

There is less evidence for women with multiple pregnancy. 1 NB Figures include women <34+0 weeks’ gestation.

 

Effects of unnecessary antenatal corticosteroids (ie if birth >7 days after steroids) are not well described.

 

While no long term harms have been proven, there have been no large studies.

35+0 to 36+6 weeks

Likely to reduce need for short term respiratory support (reduction from 146/1000 to 116/1000 RR 0.80 [0.66 to 0.97]). 3 NB Figures include women 34-36+5 weeks’ gestation.

Likely to increase neonatal hypoglycaemia (150/1000 to 240/10000 RR 1.60 [1.37 to 1.87]) 3

NB Figures include women 34-36+5 weeks’ gestation.

Lkely to increase mental and behavioural  disorders in children (HR 1.33 [1.26 to 1.41]) 7

While no long term harms have been proven, there have been no large studies.

Pre Planned CB at term <39 weeks

May decrease short term respiratory distress syndrome (reduction from 54 per 1,000 to 26 per 1,000 RR 0.48
(0.27 to 0.87) and transient tachypnoea of newborn

(reduction from 54 per 1,000 to 23 per 1,000 RR 0.43 [0.29 to 0.65]). 6

May reduce educational attainment at school age (increase in the proportion of children ranked by teachers as being in lower quartile of academic ability from 9% to 18%; and reduction in proportion of children obtaining English proficiency from 13% to 7%) 5

 

Likely to increase mental and behavioural  disorders in children (HR 1.33) 7

Risk of bias in studies means quality of evidence low.

 

Other short term complications such as hypoglycaemia have not been studied.

 

 

References for Table:

1. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2017

2. World Health Organization. WHO recommendations on interventions to improve preterm birth outcomes. Geneva, WHO; 2015

3. Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita ATN, et al. for the NICHD Maternal-Fetal Medicine Units Network. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med 2016; 374: 1311-1320

4. Sotiriadis A, McGoldrick E, Makrydimas G, Papatheodorou S, Ioannidis JPA, Stewart F, Parker R. Antenatal corticosteroids prior to planned caesarean at term for improving neonatal outcomes (Review). Cochrane Database of Systematic Reviews 2021

5. Stutchfield P, Whitaker R, Gliddon AE, Hobson L, Kotecha S, Doull IJ. Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean sections (ASTECS trial). Arch Dis Child fetal Neonatal Ed. 2013; 93, 195-200

6. Jolley JA, Rajan PV, Petersen R, Fong A, Wing DA. Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes. Diabetes Res Clin Pract 2016;118:98–104

7. Raikkonen K, Gissler M, Kajantie E. Associations between maternal antenatal corticosteroid treatment and mental and behavioral disorders in children. JAMA 200; 323: 1924-1933.

 

Are there any additional pathophysiological arguments or arguments from other patient groups or other comparable interventions that might influence decision making?

  • National clinical guidelines recommend that planned caesarean birth should not routinely be carried out before 39+0 weeks’ gestation (National Institute for Health and Care Excellence. Caesarean Section. NICE clinical guideline 132. London: NICE; 2011, updated 2019; RANZCOG. Timing of planned caesarean section at term. March 2018; Nederlandse vereniging voor Obstetrie en Gynaecologie. Indicatiestelling sectio caesarea 2011; DGGG 2020)
  • Studies from other patient groups (women not specifically undergoing planned caesarean birth – a and c)
  • No comparable interventions
  • Possibility of harm as described above

 

Values and preferences of women (and their caregivers)

What would women and their families regard as important?

  • Avoidance of long term harm and neurodevelopmental impairment
  • Avoidance of neonatal unit admission
  • Avoidance of unnecessary separation of woman and baby which interrupts the bonding process and reduces breast feeding
  • The women’s preference and values should be taken in to account with shared decision-making.
  • Parent-centred approach

 

Are there any subgroups of patients that may have different values?

  • Women who have experienced a previous preterm birth
  • Women who have previous given birth to a baby who required neonatal admission
  • Women with a multiple pregnancy

 

Costs

  • Little evidence of cost-effectiveness
  • Costs of the corticosteroid drugs is cheap
  • Costs of the outcomes (particularly neonatal special care) are expensive
  • Costs of long-term harms unknown but potentially have a high societal cost

 

Acceptability, feasibility and implementation

  • No issues regarding implementation
  • Side effects of the medications
  • The attitudes of pregnant women and their beliefs on the use of corticosteroids. One study using semi-structured interviews or questionnaires found that barriers to receipt of antenatal corticosteroids include: difficulty retaining information conveyed, requiring further information in a variety of formats, and time constraints faced by consumers and health professionals in the provision and understanding of information to facilitate decision making. Enablers to receipt of antenatal corticosteroids included: optimism towards steroid use, a strong knowledge of why steroids were administered, improved resilience in their pregnancy and confidence in their decision making following receipt of information about steroids (McGoldrick, 2016).
  • Clinical equipoise about the value of late administration of corticosteroids
  • Variability on clinicians’ practice

 

Differences between countries

In the UK, antenatal corticosteroids are generally prescribed to pregnant women before a planned caesarean section until 36+6 weeks of gestation.  After 37+0 weeks’, clinicians discuss the potential benefits and harms with women and the administration of corticosteroids is variable.

In the Netherlands and in Belgium, antenatal corticosteroids are not recommended prior to caesearan section before 39 weeks’ gestation. Clinical policy varies between hospitals.

In Germany, the Deutsche Gesellschaft für Perinatale Medizin (obstetricians-perinatologists), the German society for obstetrics and gynecology (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe) and Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (neonatologists and paediatric intensive care doctors) do not recommend the administration of corticosteroids for the prevention of respiratory problems in the baby to pregnant women after 35+0 weeks of gestation. Only in selected cases this can be considered between 34+0 and 34+6 weeks.

 

Recommendations

 

Pros and cons of antenatal corticosteroids should be discussed with women to inform shared decision-making.

 

Compared with vaginal birth, infants born by caesarean birth are at greater risk of RDS, transient tachypnoea of the newborn (TTN), and admission to the neonatal intensive care unit (NICU) (Gerten, 2005). The risk of respiratory morbidity at term is low and decreases with advancing gestational age (Vildic, 2016). Ideally, planned caesarean births should be undertaken at or after 39+0 weeks’ gestation (NICE 2019).

 

There is insufficient evidence about the effect of corticosteroid therapy in women undergoing caesarean birth from 34+0 to 36+6 weeks of gestation on RDS and admission to the neonatal intensive care unit. There is no evidence about the effect of antenatal corticosteroid therapy in pregnant women undergoing a caesarean birth from 34+0 to 36+6 weeks of gestation on perinatal mortality, neurodevelopmental disability, maternal sepsis and maternal mortality.

 

There is evidence from mixed population groups, (women undergoing planned caesarean birth and other women at risk of imminent preterm birth) that the beneficial effects of corticosteroids are present to 35+0 weeks’ gestation (McGoldrick 2021). These benefits include reductions in: perinatal death (risk ratio [RR] 0.85, 95% confidence interval [CI] 0.77–0.93), neonatal death (RR 0.78, 95% CI 0.70–0.87) and respiratory distress syndrome (RDS) (RR 0.71, 95% CI 0.65–0.78). There was moderate certainty evidence that antenatal corticosteroids reduce intraventricular haemorrhage (IVH) (RR 0.58, 95% CI 0.45– 0.75), and reduce developmental delay in childhood (RR 0.51, 95% CI 0.27–0.97).

However, steroids may result in potential harm including neonatal hypoglycaemia (Gyamfi-Bannerman, 2016).

The recommendations relating to the administration of antenatal corticosteroid therapy in pregnant women undergoing a caesarean section from 34+0 to 36+6 weeks of gestation reflect this uncertainty. The recommendations for the UK, the Netherlands and Belgium differ from those for Germany.

 

Recommendations for the UK, the Netherlands and Belgium

There should be a clear indication for undertaking a caesarean section prior to 39+0 weeks of gestation.

 

Consider the use of antenatal corticosteroid therapy in pregnant women undergoing a planned caesarean section from 34+0 to 34+6 weeks of gestation to reduce the incidence of neonatal Respiratory Distress Syndrome (RDS), bearing in mind with advancing gestation that the harms of corticosteroid treatment may outweigh the benefits.

 

Discuss the use of antenatal corticosteroid therapy in pregnant women undergoing a planned caesarean section from 35+0 to 36+6 weeks of gestation to reduce the incidence of neonatal RDS bearing in mind with advancing gestation that the harms of corticosteroid treatment may outweigh the benefits.

 

Recommendations for Germany

There should be a clear indication for undertaking a caesarean section prior to 39+0 weeks of gestation.

 

In Germany, the antenatal administration of corticosteroids if there is a risk of premature birth after 34+0 weeks of pregnancy is not recommended.

 

In rare cases, pregnant women undergoing a planned caesarean section between 34+0 and 34+6 weeks of gestation may consider using prenatal corticosteroids to reduce the incidence and severity of postnatal respiratory problems. It should be noted that as pregnancy progresses, the risks of corticosteroid treatment may outweigh the benefits.

Onderbouwing

Compared with vaginal birth, babies who have a planned caesarean birth are at greater risk of respiratory distress syndrome (RDS) (adjusted OR 2.3, 95% CI 2.1 to 2.6), transient tachypnoea of the newborn and admission to the neonatal intensive care unit (Gerten et al 2005).  The administration of maternal corticosteroids prior to planned caesarean birth may reduce the risk of neonatal respiratory morbidity. The gestational age range at which antenatal corticosteroids provide benefit remains controversial.

 

Very low GRADE

There is insufficient evidence about the effect of antenatal corticosteroid therapy in pregnant women undergoing a caesarean section from 34+0 to 36+6 weeks of gestation on RDS.

 

Sources (Kirshenbaum, 2018; Le Ray, 2006).

 

Very low GRADE

There is insufficient evidence about the effect of antenatal corticosteroid therapy in pregnant women undergoing a caesarean section from 34+0 to 36+6 weeks of gestation on NICU admission.

 

Sources (Kirshenbaum, 2018.)

 

-

GRADE

There is no evidence about the effect of antenatal corticosteroid therapy in pregnant women undergoing a caesarean section from 34+0 to 36+6 weeks of gestation on perinatal mortality, neurodevelopmental disability, maternal sepsis and maternal mortality.

Description of studies

Two observational studies were included, which reported on the population of pregnant women at gestational age of 34+0 to 36+6 weeks (Kirshenbaum, 2018; le Ray, 2006)

 

Kirshenbaum (2018) reported a case-control study (low Risk of Bias, RoB) comparing outcomes after two intramuscular doses of 12 mg betamethasone 24 hours apart 2-7 days prior to planned caesarean birth (n=58) with no corticosteroids (n=107) between groups matched for gestational age at birth, which was limited to 34+0 to 37+0 weeks.

The aim of the retrospective study by Le Ray (2006) (low RoB) was to identify risk factors for respiratory distress in 189 neonates (107 singletons and 82 twins) born by caesarean section before labour between 34+0 and 36+6 weeks of gestational age. Seventy-three neonates had been exposed to one (n=51), two (n=21) or three (n=1) courses of antenatal corticosteroids.

 

Results

The only crucial outcome reported in the included studies was RDS, with inconclusive results.

 

  1. RDS

The outcome RDS was reported by both studies. From the data reported by Kirshenbaum (2018) we calculated an OR (95% CI) of 0.68 (0.17 to 2.65); Le Ray 2006 reported an unadjusted OR (95% CI) of 0.7 (0.3 to 1.3).

 

The other crucial outcome measures were not reported in the included studies.

 

  1. NICU admission

For NICU admission in general an OR (95% CI) of 0.54 (0.17 to 1.73), p=0.2954 could be calculated from the data reported by Kirshenbaum, 2018.

 

Level of evidence of the literature

  1. The level of evidence regarding the outcome measure RDS started low and was downgraded by one level because of number of included patients (imprecision).
  2. The level of evidence regarding the outcome measure NICU admission started low and was downgraded by one level because of number of included patients (imprecision).

A systematic review of the literature was performed to answer the following questions:

 

P:        pregnant women > 34+0 completed weeks undergoing planned caesarean section;

I:         antenatal corticosteroid therapy given pre-caesarean birth;

C:        placebo or no intervention;

O:        maternal, perinatal, and long-term child outcomes: Respiratory distress syndrome, perinatal mortality and neurodevelopmental disability, maternal sepsis and mortality, NICU and neonatal unit admission, infant chronic lung disease, need for mechanical ventilation, hypoglycemia, maternal post partum infection/pyrexia.

 

In the United Kingdom, the Royal College of Obstetricians and Gynaecologists and the Royal College of Anaesthetists have proposed that the classification of urgency of caesarean birth should be categories 1 to 4, rather than elective and emergency (RCOG, 2010). For the purpose of this guideline and literature search, categories 3 and 4 are regarded as ‘planned’ procedures; category 3 is where early birth is indicated but there is no maternal or fetal compromise and category 4 is at a time to suit the woman and maternity services.

 

Relevant outcome measures

The guideline development group considered Infant Respiratory Distress Syndrome (IRDS), perinatal mortality and neurodevelopmental disability, maternal sepsis and mortality as critical outcome measures for decision making; and NICU and neonatal unit admission, infant chronic lung disease, need for mechanical ventilation, birth weight (question 3c), hypoglycemia, maternal post-partum infection /pyrexia as important outcome measures for decision making.

 

A priori, the guideline development group did not define the outcome measures listed above but used the definitions used in the studies.

 

The working group defined RR <0.99 or >1.01 as a minimal clinically important effect for mortality and <0.8 or >1.25 for all other outcomes.

 

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched using relevant search terms until August 2019. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 467 hits. Studies were selected based on the following criteria: original research or systematic reviews about pregnant women having a planned caesarean birth undergoing corticosteroid therapy compared to women having a planned caesarean birth not undergoing corticosteroid therapy. Forty-eight studies were initially selected based on title and abstract screening. After reading the full text, 43 studies were excluded (see the table with reasons for exclusion under the tab Methods (attached documents)), and two studies were included.

 

Results

Two studies were included in the analysis of the literature. Important study characteristics and results are summarized in the evidence tables (attached documents). The assessment of the risk of bias is summarized in the risk of bias tables (attached documents).

  1. Al-Rawaf, S. A., Le, A. K. J., & Alomrani, A. A. A. (2019). Effect of two separated doses of antenatal steroids at 32 weeks and five days before delivery in prevention of neonatal respiratory distress syndrome. Indian Journal of Public Health Research and Development, 10(5), 625-628.
  2. Crowther CA, Middleton PF, Voysey M, et al. Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis. PLoS Med. 2019;16(4):e1002771.
  3. di Pasquo E, Saccone G, Angeli L, Dall’Asta A, Borghi E, et al. Determinants of neonatal hypoglycaemia after antenatal administration of corticosteroids (ACS) for lung maturation: data from two referral centers and review of the literature. Early Human Development 2020; 143: 104984.
  4. Gerten KA, Coonrod DV, Bay RC, Chambliss LR. Cesarean delivery and respiratory distress syndrome: does labor make a difference? Am J Obstet Gynecol 2005; 193: 1061–1064.
  5. Gupta K, Rajagopal R, King F, Simmons D. Complications of antenatal corticosteroids in infants born by early term scheduled cesarean section. Diabetes Care 2020; 43: 906-908.
  6. Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita ATN, et al. for the NICHD Maternal-Fetal Medicine Units Network. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med 2016;374:1311–1320.
  7. Kemp MW, Jobe AH, Usuda H, Nathanielsz PW, Li C, Kuo A, Huber HF, Clarke GD, Saito M, Newnham JP, Stock SJ. Efficacy and safety of antenatal steroids. Am J Physiol Regul Integr Comp Physiol. 2018 Oct 1;315(4):R825-R839.
  8. Kirshenbaum, M., Mazaki-Tovi, S., Amikam, U., Mazkereth, R., Sivan, E., Schiff, E., & Yinon, Y. (2018). Does antenatal steroids treatment prior to elective cesarean section at 34–37 weeks of gestation reduce neonatal morbidity? Evidence from a case control study. Archives of Gynecology and Obstetrics, 297(1), 101-107.
  9. Le Ray, C., Boithias, C., Castaigne-Meary, V., l'Hélias, L. F., Vial, M., & Frydman, R. (2006). Caesarean before labour between 34 and 37 weeks: What are the risk factors of severe neonatal respiratory distress? European Journal of Obstetrics and Gynecology and Reproductive Biology, 127(1), 56-60.
  10. McGoldrick EL, Crawford T, Brown JA, Groom KM, Crowther CA. Consumers attitudes and beliefs towards the receipt of antenatal corticosteroids and use of clinical practice guidelines. BMC Pregnancy and Childbirth 2016; 16: 259
  11. McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2021;12: CD004454.
  12. McKinlay CJD, Alsweiler JM, Anstice NS, Burakevych N et al. Association of neonatal glycemia with neurodevelopmental outcomes at 4.5 years. JAMA Pediatr 2017; 17: 972-983.
  13. National Institute for Health and Care Excellence. Caesarean section. NICE clinical guideline 132. London: NICE; 2011, updated 2019.
  14. Paul, R., Murugesh, C., Chepulis, L., Tamatea, J., & Wolmarans, L. (2019). Should antenatal corticosteroids be considered in women with gestational diabetes before planned late gestation caesarean section. Australian and New Zealand Journal of Obstetrics and Gynaecology, 59(3), 463-466.
  15. Raikkonen K, Gissler M, Kajantie E. Associations between maternal antenatal corticosteroid treatment and mental and behavioral disorders in children. JAMA 200; 323: 1924-1933.
  16. Rodriguez A, Wang Y, Ali Khan A, Cartwright R, Gissler M, Järvelin MR. Antenatal corticosteroid therapy (ACT) and size at birth: A population-based analysis using the Finnish Medical Birth Register. PLoS Med. 2019;16(2):e1002746.
  17. Royal College of Obstetricians and Gynaecologists. Classification of urgency of caesarean section – A continuum of risk. Good Practice No. 11. April 2010.
  18. Savoy C, Ferro MA, Schmidt LA, Saigal S, Van Lieshout RJ.Prenatal betamethasone exposure and psychopathology risk in extremely low birth weight survivors in the third and fourth decades of life. Psychoneuroendocrinology 2016;74:278–285
  19. Sotiriadis A, McGoldrick E, Makrydimas G, Papatheodorou S, Ioannidis JPA, Stewart F, Parker R. Antenatal corticosteroids prior to planned caesarean at term for improving neonatal outcomes (Review). Cochrane Database of Systematic Reviews 2021.
  20. Stutchfield, P. R., Whitaker, R., Gliddon, A. E., Hobson, L., Kotecha, S., & Doull, I. J. (2013). Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial). Archives of Disease in Childhood-Fetal and Neonatal Edition, 98(3), F195-F200.
  21. Vidic Z, Blickstein I, Gantar IS, verdenik I, Tul N. Timing of elective cesarean section and neonatal morbidity: a population-based study. J Mat-Fetal Neonatal Med 2016; 29: 2460-2462.
  22. World Health Organization. WHO recommendations on interventions to improve preterm birth outcomes. Geneva, WHO; 2015.

 

 

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

 

Follow-up

Outcome measures and effect size

Comments

Kirshenbaum 2018

Type of study: case-control study

 

Setting and country: single tertiary medical center, Israel

 

Funding: none

Conflicts of interest: none declared

Inclusion criteria:

elective caesarean section

34+0 to 37+0 weeks GA

Exclusion criteria:

multiplets, congenital anomalies, chromosomal abnormalities, chorioamnionitis

 

N total at baseline:

Intervention: 58

Control: 107

 

Important prognostic factors2:

hypertensive disease in pregnancy

I: 5 (9%)

C: 21 (20%)

 

Groups comparable at baseline? No

 

Describe intervention (treatment/procedure/test):

2 im doses of 12 mg betamethasone 24 hours apart 2-7 days prior to delivery

 

 

 

Describe  control (treatment/procedure/test):

no corticosteroids

 

Length of follow-up:

not reported

 

Loss-to-follow-up:

not reported

 

Incomplete outcome data:

not reported

 

 

Outcome measures and effect size (include 95%CI and p-value if available):

 

composite respiratory morbidity outcome defined as the presence of either RDS, TTN, mechanical ventilation or

oxygen requirement

I: 14/58 (24%), C: 26/107 (24%), p=0.98

Multivariable logistic regression:

OR [95% CI) adjusted for birth weight, GDM, indication for delivery, GA at delivery and gender: 0.85 [0.83; 1.07], p=0.4

 

RDS

I: 3/58 (5%), C: 8/107 (8%), p=0.57

OR [95% CI]  0.68 [0.17; 2.65]

 

TTN

I:6/58 (10%), C: 12/107 (11%), p=0.86

OR [95% CI] 0.91 [0.32; 2.58]

 

NICU admission

I: 4/58 (7%), C: 13/107 (12%), p=0.30

OR [95% CI] of 0.54 [0.17; 1.73]

 

groups matched for gestational age at delivery

most important prognostic factors for composite respiratory morbidity outcome:

GA at delivery and gender

le Ray 2006

Type of study:

retrospective study

 

Setting and country: level 3 reference centre France

 

Funding and conflicts of interest: Not reported

Inclusion criteria:

caesarean delivery before labour

GA 34+0 to 36+6 weeks

Exclusion criteria:

caesareans during or at the onset of labour, following induction or cervical ripening,

triplets or more, infants with serious malformations

 

N total at baseline:

Intervention: 73

Control: 116

 

Important prognostic factors2:

mean GA

I: 35.3 weeks

C: 35.8 weeks

 

Groups comparable at baseline? No, I: lower GA, more twins

 

Describe intervention (treatment/procedure/test):

 

antenatal corticosteroids (1, 2 or 3 courses)

 

 

Describe  control (treatment/procedure/test):

 

no antenatal corticosteroids

Length of follow-up:

not reported

 

Loss-to-follow-up:

not reported

 

Incomplete outcome data:

not reported

 

 

Outcome measures and effect size (include 95%CI and p-value if available):

 

severe respiratory distress

unadjusted OR [95% CI] 0.7 [0.3; 1.3]

aim of the study was to identify risk factors for respiratory distress; gestational age, ruptured membranes, singleton pregnancy, fetal indication for caesarean and birth weight were identified

 

 

 

 

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)

Kirshenbaum 2018

unlikely

unlikely

unlikely

unlikely

le Ray 2006

unclear

unlikely

unlikely

unlikely

 

 

 

Table of excluded studies

 

First author, year

reason for exclusion

Abbasi, 2000

no separate data for caesarean section

Afzal, 2019

excluded from SR Sotiriadis 2021

Ahmed, 2015

included in SR Sotiriadis 2018, excluded from Sotiriadis 2021

Aiken, 2014

long-term results of RCT Stutchfield 2005 (included in SR Sotiriadis 2018)

Al-Rawaf, 2019

I different from PICO

Altman, 2013

no separate data for caesarean section

Amiya, 2016

SR, no studies included for this PICO

Cartwright 2018

P (< 32 wks GA) different from PICO

Collins 2019

guideline, no original data

Crowther, 2015

SR, no separate data for caesarean section

De Vivo, A. 2010

prednison for prevention anaphylactic reactions

Dileep, 2015

no RCT

Groom, 2019

narrative review

Gyamfi-Bannerman, 2012

no separate data for caesarean section

Haas, 2011

P (preterm birth) different from PICO

Haas, 2008

P (preterm birth) different from PICO

Kaempf, 2017

commentary

Kamath-Rayne, 2012

no separate data for caesarean section

Kamath-Rayne, 2016

narrative review

Krispin, 2018

no separate data for caesarean section

Khushdil, 2018

no RCT

Lassi, 2015

no separate data for caesarean section

Mahmoud, 2018

no RCT

McLaughlin, 2004

no separate data for caesarean section

McKenna 2000

outcome: maternal adrenal suppression

Mirzamoradi 2019

excluded from SR Sotiriadis 2021

Nada, 2016

included in SR Sotiriadis 2018, excluded from Sotiriadis 2021

Nooh, 2018

included in SR Sotiriadis 2018, excluded from Sotiriadis 2021

Ontela, 2018

no separate data for caesarean section

Paganelli, 2013

narrative review of biochemical and physiological principles

Paul, 2019

I different from PICO

Pole, 2010

no separate data for caesarean section

Saccone, 2016

SR, for this PICO 3 studies included that were also included by Sotiriadis 2018

Sananès, 2017

excluded from SR Sotiriadis 2021

Shaughnessy, 2017

summary of Saccone 2016

Skoll, 2018

guideline, no original data

Sotiriadis, 2007

earlier version of SR Sotiriadis 2021

Sotiriadis, 2009

earlier version of SR Sotiriadis 2021

Sotiriadis, 2018

earlier version of SR Sotiriadis 2021

Sotiriadis, 2021

I different from PICO

Soysal, 2016

narrative review

Srinivasjois, 2017

SR, 3 studies included that were also included by Sotiriadis 2018

Steer, 2005

editorial

Stutchfield, 2005

included in SR Sotiriadis 2021

Stutchfield, 2013

included in SR Sotiriadis 2021

Ting, 2018

narrative review

 

Autorisatiedatum en geldigheid

Laatst beoordeeld  : 30-12-2022

Laatst geautoriseerd  : 30-12-2022

Geplande herbeoordeling  :

The Board of the Dutch Society of Obstetrics and Gynaecology (NVOG) will assess whether these guidelines are still up-to-date in 2027 at the latest. If necessary, a new working group will be appointed to revise the guideline. The guideline’s validity may lapse earlier if new developments demand revision at an earlier date.

As the holder of this guideline, the NVOG is chiefly responsible for keeping the guideline up to date. Other scientific organizations participating in the guideline or users of the guideline share the responsibility to inform the chiefly responsible party about relevant developments within their fields.

Initiatief en autorisatie

Initiatief:
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
Geautoriseerd door:
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Patiëntenfederatie Nederland

Algemene gegevens

Er is meegelezen vanuit de Nederlandse Vereniging voor Kindergeneeskunde (NVK). De NVK heeft de richtlijn niet geautoriseerd, maar heeft geen bezwaar tegen publicatie.

De Koninklijke Nederlandse Organisatie van Verloskundigen (KNOV) is betrokken geweest bij de ontwikkeling van de richtlijn.

De Patiëntenfederatie Nederland heeft de richtlijn goedgekeurd.

De Vlaamse Vereniging voor Obstetrie en Gynaecologie (VVOG), Royal College of Obstetrics and Gynaecology (RCOG) en Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) zijn betrokken geweest bij de ontwikkeling van de richtlijn.

Samenstelling werkgroep

An international panel for the development of the guidelines was formed in 2019. The panel consisted of representatives from all relevant medical disciplines that are involved in medical care for pregnant women.

All panel members have been officially delegated for participation in the guideline development panel by their (scientific) societies. The panel developed the guidelines in the period from May 2019 until March 2021.

The guideline development panel is responsible for the entire text of this guideline.

 

Composition guideline development panel

 

All panel members have been officially delegated for participation in the guideline development panel by their scientific societies. The guideline development panel is responsible for the entire text of this guideline.

 

Guideline development panel

  • J.J. Duvekot, obstetrician, Consultant Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, the Netherlands (chair)
  • I. Dehaene, obstetrician, Consultant Obstetrics and Gynaecology, Ghent University Hospital Belgium
  • S. Galjaard, obstetrician, Consultant Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, the Netherlands
  • A. Hamza, obstetrician, Consultant Obstetrics and Gynaecology, University Medical Center of Saarland, Homburg an der Saar, Germany
  • S.V. Koenen, obstetrician, Consultant Obstetrics and Gynaecology, ETZ, locatie Elisabeth Ziekenhuis Tilburg, the Netherlands
  • M. Kunze, obstetrician, Consultant Obstetrics and Gynaecology, Department of Gynecology& Obstetrics University of Freiburg, Germany
  • M.A. Ledingham, obstetrician, Consultant Obstetrics and Gynaecology, the Queen Elizabeth Hospital Glasgow, UK
  • B. Magowan, obstetrician, Consultant Obstetrics and Gynaecology, and Co-Chair UK RCOG Guidelines Committee, NHS Borders, Scotland, UK
  • G. Page, obstetrician, Consultant Obstetrics and Gynaecology, Jan Yperman Hospital, Ypres, Belgium
  • S.J. Stock, Reader and Consultant in Maternal and Fetal Medicine, University of Edinburgh Usher Institute and NHS Lothian, Edinburgh, Scotland, UK
  • A.J. Thomson, obstetrician, Consultant Obstetrics and Gynaecology, Royal Alexandra Hospital (NHS Greater Glasgow and Clyde), UK
  • G. Verhulst, obstetrician, Consultant Obstetrics and Gynaecology, ASZ Aalst/Geraardsbergen/Wetteren, Belgium
  • D.C. Zondag, midwife/practice owner verloskundige praktijk De Toekomst-Geldermalsen, the Netherlands

 

Methodological support

  • E. den Breejen, senior advisor, Knowledge Institute of the Dutch Association of Medical Specialists (until June 2019)
  • J.H. van der Lee, senior advisor, Knowledge Institute of the Dutch Association of Medical Specialists (since May 2019)
  • Y. Labeur, junior advisor, Knowledge Institute of the Dutch Association of Medical Specialists

Belangenverklaringen

Declarations of interests

The Code for the prevention of improper influence due to conflicts of interest was followed (https://storage.knaw.nl/2022-08/Code-for-the-prevention-of-improper-influence-due-to-conflicts-of-interest.pdf).

The working group members have provided written statements about (financially supported) relations with commercial companies, organisations or institutions related to the subject matter of the guideline during the past three years. Furthermore, inquiries have been made regarding personal financial interests, interests due to personal relationships, interests related to reputation management, interest related to externally financed research and interests related to knowledge valorisation. The chair of the guideline development panel is informed about changes in interests during the development process. The declarations of interests are reconfirmed during the commentary phase. The declarations of interests can be requested at the administrative office of the Knowledge Institute of the Dutch Association of Medical Specialists and are summarised below.

 

 

Last name

Principal position

Ancillary position(s)

Declared interests

Action

Duvekot (chair)

Consultant Obstetrics and Gynaecology, Erasmus MC, Rotterdam

Director Medisch Advies en Expertise Bureau Duvekot, Ridderkerk

none

none

Dehaene

Consultant Obstetrics and Gynaecology, Ghent University Hospital

none

none

none

Galjaard

Consultant Obstetrics and Gynaecology, Erasmus MC, Rotterdam

Associated member of Diabetes in Pregnancy Group (DPSG)

none

none

Hamza

Consultant Obstetrics and Gynaecology, University Medical Center of Saarland, Homburg

part of the advisory board of clinical innovations, which produces Kiwi-Vacuum Extractors® and Ebb Balloon Catheter®;

 

gave ultrasound courses sponsored by

ultrasound producing companies: Samsung Germany and Matramed

Recommendations do not involve either vacuum extractor or Ebb catheter (which is used for postpartum hemorrhage); therefore no actions

Koenen

Consultant Obstetrics and Gynaecology, ETZ, locatie Elisabeth Ziekenhuis Tilburg

Chairman 'Koepel Kwaliteit' NVOG

none

none

Kunze

Divison Chief, Maternal-Fetal Medicine and Obstetrics, Departement of Gynecology & Obstetrics, University of Freiburg

none

none

none

Ledingham

Consultant in Maternal and Fetal Medicine, Queen Elizabeth Hospital, Glasgow

Co-chair RCOG Guidelines committee, Guideline developer for sign (scottisch intercollegiate guidelines group)

none

none

Magowan

Consultant Obstetrics and Gynaecology, and Co-Chair UK RCOG Guidelines Committee, NHS Borders, Scotland

Co-chair RCOG Guidelines committee

none

none

Page

Consultant Obstetrics and Gynaecology, Jan Yperman Hospital, Ypres

none

none

none

Stock

Reader and Consultant in Maternal and Fetal Medicine, University of Edinburgh and NHS Lothian, Edinburgh, Scotland, UK

Consultant Obstetrician and Subspecialist Maternal and Fetal Medicine,

member of the NIHR HTA General committee (grant funding board) and Chair of the

RCOG Stillbirth Clinical Studies Group

Research grants paid to the institution for research into pregnancy problems from

National Institute of Healthcare Research (NIHR) Health Technology Assessment (HTA),

NIHR Global Research Fund, Wellcome Trust, Medical Research Council, Tommy's Baby Charity,

Cheif Scientist Office Scotland. Some of this work focuses on improving risk prediction of preterm labour

and researching the benefits and harms of antenatal corticosteroids. Non-financial support from HOLOGIC, non-financial support from PARSAGEN, non-financial support from MEDIX BIOCHEMICA during the conduct of an NIHR HTA study in the form of provision of reduced cost assay kits to participating sites and blinded test assay analysers

none

Thomson

Consultant Obstetrics and Gynaecology, Royal Alexandra Hospital (NHS Greater Glasgow and Clyde)

Guideline developer for the RCOG

none

none

Verhulst

Head of Department of Gynaecology and Obstetrics, ASZ Aalst/Geraardsbergen/Wetteren

none

none

none

Zondag

Midwife/practice owner verloskundige praktijk De Toekomst-Geldermalsen

Policy adviser at the Dutch association of midwives (KNOV). Teacher at PA clinical midwives - Hogeschool Rotterdam

none

none

 

Inbreng patiëntenperspectief

Involvement of patient representatives from all four participating countries was challenging. Representatives of patient organisations from three countries (UK, Belgium, the Netherlands) commented on the draft guideline texts and discussed these during an online meeting. They represented the RCOG Women’s Network, the Flemish organisation for people with fertility problems ‘De verdwaalde ooievaar’, the Netherlands Patient Federation, and the Dutch association for people with fertility problems ‘Freya’. The comments were discussed and where relevant incorporated by the guideline development panel.

Methode ontwikkeling

Evidence based

Implementatie

Guideline implementation and practical applicability of the recommendations was taken into consideration during various stages of guideline development. Factors that may promote or hinder implementation of the guideline in daily practice were given specific attention.

 

The guideline is distributed digitally among all relevant professional groups. The guideline can also be downloaded from the following websites: www.nvog.nl, www.vvog.be, www.rcog.org.uk, www.dggg.de, and the Dutch guideline website: www.richtlijnendatabase.nl.

Werkwijze

AGREE

This guideline has been developed conforming to the requirements of the report of Guidelines for Medical Specialists 2.0 by the advisory committee of the Quality Counsel. This report is based on the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II) (www.agreetrust.org)(Brouwers, 2010), a broadly accepted instrument in the international community and on the national quality standards for guidelines: “Guidelines for guidelines” (www.zorginstituutnederland.nl).

 

Identification of subject matter

During the initial phase of the guideline development the chairman, guideline development panel and the advisor inventoried the relevant subject matter for the guideline. Since this was a pilot project, the content of the questions and the support base in clinical practice was considered of less importance than the process of international collaboration and learning from each other. Key questions were selected in such a way that:

  • they were relevant for obstetric practice in all collaborating countries;
  • it was expected that the amount of literature identified for each question would be reasonable, i.e. some literature was expected, but not much;
  • the recommendations were expected not to lead to extensive discussion among working group members because no major controversy was expected;
  • there were no recent guidelines available for these particular topics in any of the four countries.

 

Clinical questions and outcomes

The guideline development panel then formulated definitive clinical questions and defined relevant outcome measures (both beneficial and harmful effects). The working group rated the outcome measures as critical, important and not important. Furthermore, where applicable, the working group defined relevant clinical differences.

 

Strategy for search and selection of literature

For the separate clinical questions, specific search terms were formulated and published scientific articles were searched for in (several) electronic databases. Furthermore, studies were scrutinized by cross-referencing for other included studies. The studies with potentially the highest quality of research were searched for first. The panel members selected literature in pairs (independently of each other) based on title and abstract. A second selection was performed based on full text. The databases, search terms and selection criteria are described in the modules containing the clinical questions.

 

Quality assessment of individual studies

Individual studies were systematically assessed, based on methodological quality criteria that were determined prior to the search, so that risk of bias could be estimated. This is described in the “risk of bias” tables.

 

Summary of literature

The relevant research findings of all selected articles are shown in evidence tables. The most important findings in literature are described in literature summaries. In case there were enough similarities between studies, the study data were pooled.

 

Grading quality of evidence and strength of recommendations

The strength of the conclusions of the scientific publications was determined using the GRADE-method. GRADE stands for Grading Recommendations Assessment, Development and Evaluation (see http://www.gradeworkinggroup.org/).

GRADE defines four gradations for the quality of scientific evidence: high, moderate, low or very low. These gradations provide information about the amount of certainty about the literature conclusions (http://www.guidelinedevelopment.org/handbook/).

 

The basic principles of the GRADE method are: formulating and prioritising clinical (patient) relevant outcome measures, a systematic review for each outcome measure, and appraisal of the evidence for each outcome measure based on the eight GRADE domains (domains for downgrading: risk of bias, inconsistency, indirectness, imprecision, and publication bias; domains for upgrading: dose-effect association, large effect, and residual plausible confounding).

 

GRADE distinguishes four levels for the quality of the scientific evidence: high, moderate, low and very low. These levels refer to the amount of certainty about the conclusion based on the literature, in particular the amount of certainty that the conclusion based on the literature adequately supports the recommendation (Schünemann, 2013; Hultcrantz, 2017).

 

GRADE

Definition

High

  • We are very confident that the true effect lies close to that of the estimate of the effect.
  • it is very unlikely that adding results of large new studies will change the conclusion in a clinically relevant way.

Moderate

  • We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different;
  • it is possible that adding results of large new studies will change the conclusion in a clinically relevant way.

Low

  • Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect;
  • it is likely that adding results of large new studies will change the conclusion in a clinically relevant way.

Very low

  • We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect;
  • the conclusion based on the literature is very uncertain.

For the wording of the conclusions we used the statements suggested by the GRADE working group (Santesso, 2020), as shown below.

Source: Santesso (2020)

 

The limits of clinical decision making are very important in grading the evidence in guideline development according to the GRADE methodology (Hultcrantz, 2017). Exceedance of these limits would give rise to adaptation of the recommendation. All relevant outcome measures and considerations need to be taken into account to define the limits of clinical decision making. Therefore, the limits of clinical decision making are not one to one comparable to the minimal clinically relevant difference. In particular for interventions of low costs and without important drawbacks the limit of clinical decision making regarding the effectiveness of the intervention may be lower (i.e. closer to no effect) than the Minimal Clinically Important Difference (MCID) (Hultcrantz, 2017).

 

Considerations (evidence to decision)

Aspects such as expertise of working group members, patient preferences, costs, availability of facilities, and organisation of healthcare aspects are important to consider when formulating a recommendation. For each clinical question, these aspects are discussed in the paragraph Considerations, using a structured format based on the evidence-to-decision framework of the international GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello, 2016b). The evidence-to-decision framework is an integral part of the GRADE methodology.

 

Formulating recommendations

Recommendations provide an answer to the primary question, and are based on the best scientific evidence available and the most important considerations. The level of scientific evidence and the importance given to considerations by the working group jointly determine the strength of the recommendation. In accordance with the GRADE method, a low level of evidence for conclusions in the systematic literature review does not rule out a strong recommendation, while a high level of evidence may be accompanied by weak recommendations. The strength of the recommendation is always determined by weighing all relevant arguments.

 

Knowledge gaps

During the development of this guideline, systematic searches were conducted for research contributing to answering the primary questions. For each primary question, the working group determined whether (additional) scientific research is desirable.

 

Commentary and authorisation phase

The concept guideline was subjected to commentaries by the scientific societies and patient organisations involved. The draft guideline was also submitted to the following organisations for comment: RCOG Guideline Committee and RCOG Patient Information Committee, German Neonatology and Peaediatric Intensive Care Association (Gesellschaft für Neonatologie und pädiatrische Intensivmedzin e.V.), German Midwives Society (Deutscher Hebammenverband), Flemish Midwives Society (VBOV), Belgian Federal Knowledge Centre for Health Care (KCE), Flemish College of Maternity and Neonatal Medicine (College Moeder Kind), Flemish patient organization for fertility problems (De Verdwaalde Ooievaar), Dutch Pediatric Society (NVK), Dutch College of General Practitioners (NHG), Healthcare Insurers Netherlands (ZN), The Dutch Healthcare Authority (NZA), the Health Care Inspectorate (IGJ), Netherlands Care Institute (ZIN), Dutch Organisation of Midwives (KNOV), Hospital organization (NVZ), Patient organisations Dutch Patient Federation and Freya. The comments were collected and discussed with the working group. The feedback was used to improve the guideline; afterwards the working group made the guideline definitive. The final version of the guideline was offered for authorization to the involved scientific societies and patient organisations and was authorized or approved, respectively.

 

Legal standing of guidelines

Guidelines are not legal prescriptions but contain evidence-based insights and recommendations that care providers should meet in order to provide high quality care. As these recommendations are primarily based on ‘general evidence for optimal care for the average patient’, care providers may deviate from the guideline based on their professional autonomy when they deem it necessary for individual cases. Deviating from the guideline may even be necessary in some situations. If care providers choose to deviate from the guideline, this should be done in consultation with the patient, where relevant. Deviation from the guideline should always be justified and documented.

Zoekverantwoording

Zoekacties zijn opvraagbaar. Neem hiervoor contact op met de Richtlijnendatabase.

Volgende:
Corticosteroiden bij geplande sectio tussen 37+0 en 39+0 weken zwangerschapsduur