Journal Club Papers
Evaluation of Long-term Outcomes Associated With Preterm Exposure to Antenatal Corticosteroids: A Systematic Review and Meta-analysis. Ninan et al. JAMA Pediatrics. 11 April 2022.
This systematic review and meta-analysis examined long-term offspring outcomes by gestation at birth following preterm steroid exposure: extremely preterm birth, preterm birth and term birth.
There were 30 cohort studies that included over 1.25 million children. All were at least 1 year old at the time of assessment. The primary outcome was a composite of any neurodevelopmental and/or psychological disorder.
Children born extremely preterm (<34 weeks’ gestation):
- A single course of antenatal corticosteroids was associated with a significant reduction in the likelihood of neurodevelopmental impairment (2 studies; aOR 0.69 [95% CI 0.57, 0.84], low certainty) and cerebral palsy (2 studies; aOR 0.60 [95% CI 0.43, 0.83], low certainty). There was no difference in auditory or visual impairment between exposed and unexposed children.
Children born preterm (<37 weeks’ gestation):
- Exposure to antenatal corticosteroids (unspecified number of courses), compared with no exposure, was not associated with a significant reduction in the likelihood of neurodevelopmental impairment (5 studies; aOR 0.78 [95% CI 0.57, 1.06], low certainty of evidence).
Children born at term:
- Two studies reported that 45.3% and 47.9% of children were born at term following preterm exposure to corticosteroids. Among those who birthed at term, preterm corticosteroid exposure was associated with a 47% increased risk of any mental or behavioural disorder, (2 studies, 614,487 children; aHR 1.47 [95% CI 1.36, 1.60]), low certainty) and a higher risk of investigations for neurodevelopmental impairment (529,205 children; aHR 1.12 [95%CI 1.08-1.16], low certainty).
- For context, the estimated baseline prevalence of behavioural disorders and mental illness among children (aged 4-11 years) in Australia is 14% (AIHW) so a 1.47 times increased risk is potentially significant.
These findings suggest appropriate patient selection, while difficult, may be important for the true benefit of antenatal steroids to be seen.
Children who received antenatal corticosteroids and were born preterm had a significantly lower likelihood of neurodevelopmental impairment. However, the findings suggested that those exposed to steroids preterm but born at term did not receive a benefit, and may also be at a significantly higher risk of neurodevelopmental impairment.
Treatment for Mild Chronic Hypertension during Pregnancy. Tita et al. New England Journal of Medicine. 12 May 2022.
Chronic hypertension is associated with pregnancy complications including pre-eclampsia, placental abruption, and preterm birth. It remains unclear whether treating mild to moderate hypertension in pregnancy improves maternal and neonatal outcomes.
This United States-based multi-centre randomised control trial recruited 2408 pregnant women with mild chronic hypertension (blood pressure (BP) 140/90 – 160/105) prior to 23 weeks’ gestation.
Women were randomised to the control group with no treatment unless severe hypertension (BP ≥160/105) developed (n=1200) or treatment of mild hypertension(treatment group), (managed with labetalol (61.7%), extended release nifedipine (35.6%) or other (2.7%)), aiming for a target blood pressure <140/90 (n=1208).
The primary outcome was a composite of severe pre-eclampsia, medically-indicated delivery ≤35 weeks, placental abruption, or perinatal death. Secondary outcomes included a composite of maternal death or serious complications, any preterm birth (<37 weeks’ gestation), and a second composite of serious neonatal complications.
Treating mild hypertension was associated with marginally lower mean blood pressures, with systolic readings 3.1mmHg and diastolic readings 2.3mmHg lower in the treatment group compared with control.
- There was a significant reduction in primary outcome events (aRR 0.82 (95%CI, 0.74-0.92), p<0.001) in the treatment group. Specifically, the treatment group had a lower incidence of severe pre-eclampsia (aRR 0.80 (95%CI, 0.70-0.92)) and preterm birth <35 weeks (aRR 0.73 (95%CI 0.60-0.89)). The incidence of any pre-eclampsia (severe or otherwise) was also lower in the treatment group; 24.4% compared with 31.1% in the control (RR 0.79 (95%CI 0.69-0.89).
- To prevent one primary outcome event, between 14 and 15 women (14.7; 95%CI, 9.4-33.7) with mild hypertension required treatment.
- The incidence of the secondary maternal and neonatal composite outcomes did not significantly differ between the control and treatment groups.
Antihypertensive use for mild hypertension has been previously associated with small for gestational age (SGA) infants. Reassuringly, this association was not found in this study (aRR 1.04 (95% CI 0.82-1.31, p=0.76).
Almost half of the sample (47.5%) were non-Hispanic black women, and only one in 12 women screened for the trial met inclusion criteria. This is not the ethnic mix in Australia or many other countries.
Nonetheless, this paper should provide guidance for clinicians as to the safety and potential benefit of treatment of chronic mild hypertension in pregnancy (rather than withholding medications until the hypertension is severe).
Effect of Self-monitoring of Blood Pressure on Blood Pressure Control in Pregnant Individuals With Chronic or Gestational Hypertension: The BUMP 2 Randomized Clinical Trial. JAMA. Chappell et al. 3 May 2022.
This study comes from the queen of practical, translatable RCTs and friend of GOU, Professor Lucy Chappell. Conducted across 15 maternity units in the UK, this study aimed to assess whether self-monitoring of blood pressure at home by women with hypertension in pregnancy could lead to better blood pressure control, compared with usual antenatal care. 850 women with chronic or gestational hypertension prior to 37 weeks’ gestation were recruited.
- Chronic hypertension was defined as sustained blood pressure >=140mmHg systolic and/or >=90mmHg diastolic at booking or prior to 20 weeks’ gestation, or ongoing treatment with antihypertensive medication outside of pregnancy
- Gestational hypertension was defined as sustained blood pressure >=140mmHg systolic and/or >=90mmHg diastolic after 20 weeks’ gestation
- Individuals likely to deliver within 48 hours of eligibility assessment were excluded
- 430 women assigned to self-monitoring (intervention group) using a validated telemonitoring system, in addition to usual care
- 420 women were assigned to usual care (control group) with blood pressure measured by health professionals at regular antenatal care visits
The primary outcome was a difference in mean systolic blood pressure (recorded by health care professionals) between randomisation and birth.
- Self-monitoring of blood pressure (intervention) did not result in a statistically significant difference in the primary outcome – the adjusted mean difference in systolic blood pressure was 0.03mmHg among the chronic hypertension group and -0.03mmHg among the gestational hypertension group between randomisation and birth
- Serious adverse events were defined as pre-eclampsia, placental abruption, transient ischemic attack or stroke, pulmonary oedema, renal failure, blood transfusion), death
- There were 8 serious adverse events in the intervention group (4 in each cohort) and 3 in the usual care group
- This was not a statistically significant difference within either the chronic hypertension (p=0.69) or gestational hypertension (p=0.21) groups
The trial did not show that the use of blood pressure monitoring with telemonitoring improves clinic-based blood pressure control.
- The authors acknowledge however that the effect of the intervention may have been diluted by the numbers of women already self-monitoring their blood pressure prior to recruitment (66% of women with chronic hypertension and 43% of women with gestational hypertension).
This study was not designed to assess the ‘safety’ of self-monitoring of blood pressure. However, the consistency in measurements of blood pressure between the randomised groups and the lack of difference in risk of adverse outcomes, suggests that home blood pressure monitoring in conjunction with usual care may have a role in the future management of women with established hypertension in pregnancy.