Association between hypertensive disorders and Bell’s palsy in pregnancy: protocol for a systematic review and meta-analysis

Abstract

Background

Bell’s palsy is an idiopathic peripheral nerve palsy involving the facial nerve. Pregnancy, diabetes mellitus and hypertension are the risk factors for Bell’s palsy. However, the association between hypertensive disorders and Bell’s palsy during pregnancy or the puerperium remains unclear. This systematic review will comprehensively summarise the literature and evaluate the association between Bell’s palsy and hypertensive disorders during pregnancy or the puerperium.

Methods and analysis

Systematic searches of PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be undertaken using prespecified search strategies. Observational studies (cross-sectional studies, cohort studies, case reports and series case reports) written in English that investigate the association between hypertensive disorders of late pregnancy and Bell’s palsy during pregnancy or the puerperium will be included. Different authors will independently conduct the eligible study selection, perform data extraction and appraise the quality of included studies. Subgroup analysis will be carried out based on the age of pregnant women (≤35 years old, >35 years old), parity (primipara, multipara) and fetus number (singleton or multiple-gestation pregnancy).

Ethics and dissemination

This review will be based on published literature, and thus there is no requirement for ethics approval. The results of this study will aid in the knowledge of the relationship between Bell’s palsy during pregnancy or the puerperium and hypertensive disorders of late pregnancy. The results of this systematic review will be shared through publication in a peer-reviewed journal with good visibility for the field of obstetrics and presentations at academic conferences.

PROSPERO registration number

CRD42023422902.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• This will be the first systematic review and meta-analysis to evaluate the association between Bell’s palsy and gestational hypertension during pregnancy or the puerperium.

• Due to the low incidence of Bell’s palsy during pregnancy, the potentially eligible studies may lack sufficient effective information and generally have small samples. This might introduce a possibility for bias.

• There is a degree of heterogeneity anticipated between studies attributed to different study settings.

Introduction

Bell’s palsy is an acute-onset peripheral facial neuropathy that affects muscles of facial expression, accompanied by less common symptoms of jaw or ear pain, hyperacusis on the affected side and dysgeusia. It can occur at any age, with a median onset age of 40 years. The annual incidence of Bell’s palsy in the population was 0.02–0.03%.¹ Pregnant women are affected 3.3 times more often than non-pregnant women,^{2 3} and it presents almost exclusively in the third trimester of pregnancy or puerperium.^{2 4} Infection, immunosuppression and ischaemic mechanisms are all potential factors for the development of Bell’s palsy, but the exact causes remain inconclusive.^{2 5} Old age, hypertension, loss of taste and pregnancy are risk factors for the poor prognosis of Bell’s palsy.^{1 6} There is currently no clear evidence that patients with hypertensive disorders complicating pregnancy are at higher risk of developing Bell’s palsy or have a worse prognosis compared with women without hypertension. As the onset time of pregnancy-associated Bell’s palsy is the same as that of late pregnancy-associated disorders, such as gestational hypertension, pre-eclampsia/eclampsia and gestational diabetes mellitus, some studies speculate that the pathogenesis of Bell’s palsy is similar to that of late pregnancy-associated disorders, but that different conditions and specific inducing factors can lead to different clinical manifestations.^{7 8} Bell’s palsy presents the same symptoms in pregnant and non-pregnant women, but the course of pregnancy is usually more severe, and it is even more likely to develop into complete facial paralysis. So, compared with pregnant women without hypertension, the incidence and prognosis of Bell’s palsy in patients with hypertensive diseases during pregnancy or puerperium require further investigation.

Hypertensive disorder complicating pregnancy, especially pre-eclampsia, has various manifestations. While a wide variety of causes, such as cerebrovascular accidents, may be implicated in Bell’s palsy during pregnancy or the puerperium, it is of utmost importance to screen for pre-eclampsia.^{9 10} Bell’s palsy may be a predictor or the first sign of pre-eclampsia and indicates increased severity of the disease, warranting appropriate investigations and close monitoring.^{4 8 11} Some studies have suggested that Bell’s palsy increases the risk of hypertensive disorder during pregnancy, whereas the pregnant state, in turn, may affect the course and severity of the disease.² Current studies recommend steroid therapy at an early stage of Bell’s palsy.¹² However, due to the concern about the side effects of steroids on mother and fetus, some clinicians have been conservative about using steroids to treat women during pregnancy. This may be the cause of the poor prognosis of Bell’s palsy during pregnancy.

The occurrence of Bell’s palsy during pregnancy or puerperium may be related to the development of hypertensive disorder complicating pregnancy. This systematic review and meta-analysis will summarise the existing evidence to test these correlations. Because of the rarity of Bell’s palsy during pregnancy, only a few retrospective studies have studied it, and even fewer studies have been conducted on the association between Bell’s palsy and hypertension. The rarity limits the ability to examine the relationship between Bell’s palsy and higher blood pressure during pregnancy in a large sample of multicentre studies; this paper hopes to explore the relationship through systematic analysis. This systematic review aims to raise obstetricians’ attention to Bell’s palsy and the relationship between Bell’s palsy and hypertensive disorders during pregnancy or puerperium.

Review question

Do pregnant women with hypertensive disorder during pregnancy or puerperium have a higher risk or worse prognosis of Bell’s palsy than those without hypertensive disorder?

Materials and methods

Protocol and registration

This review protocol was drafted by using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidance (online supplemental file 1)¹³ and has been registered on the International Prospective Register of Systematic Reviews (CRD42023422902). The systematic review and meta-analysis will be conducted in accordance with the Meta-analyses Of Observational Studies in Epidemiology guidelines.¹⁴

Eligibility criteria

Population

Pregnant women with no prior hypertensive disorders before pregnancy.

Exposures

The exposure of interest is the presence of gestational hypertension including pre-eclampsia, eclampsia and HELLP syndrome.

1. Gestational hypertension is an elevation of blood pressure (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) after 20 weeks of gestation without proteinuria, and returns to normal by 12 weeks post partum.

2. Pre-eclampsia is defined as gestational hypertension accompanied by at least one of the following new-onset conditions: (a) proteinuria (1+ proteinuria on a urine dipstick test, or in a 24-hour urine collection protein ≥0.3 g or a protein/creatinine ratio ≥0.3); (b) maternal organ dysfunction (such as thrombocytopenia, acute kidney injury, liver complications, neurological complications).¹⁵

3. Eclampsia is defined as unexplained seizures on the basis of pre-eclampsia.¹⁶

4. HELLP syndrome is defined as haemolysis, elevated liver enzymes and low platelet count syndrome.¹⁷

Comparation

Pregnant women with no gestational hypertension.

Outcome

The outcome of interest is the onset of Bell’s palsy during the late pregnancy or until 6 weeks post partum.

Study design

This project will include all prospective or retrospective observational studies, including case-control, nested case-control, cross-sectional, case-cohort and cohort studies, which have evaluated the association between the exposure and outcome(s) of interest.

Search strategy

PubMed, MEDLINE (Ovid), Embase (Ovid) and the Cochrane Central Register of Controlled Trials will be searched. Any potentially eligible studies published in English will be considered for inclusion. The search strategies are shown in the online supplemental file 2. Reference lists of all included studies will be manually searched for any other eligible studies.

Selection of studies

All search results will be imported into the reference management software EndNote. Two researchers will independently remove duplicates and screen the titles and abstracts for relevance. Following this, the full-text articles of potentially relevant records will be retrieved and collated in a Microsoft Excel spreadsheet for assessment against the inclusion criteria. The reason for exclusion will be documented. A third reviewer (SZ) will be consulted to resolve any conflicts throughout the review process.

Inclusion criteria

1. Cross-sectional, case-control, nested case-control, case-cohort and cohort studies.

2. Data must be from an original study.

3. Only English-language studies published will be considered for inclusion.

4. Human studies and peer-reviewed papers only will be included.

5. Studies that provide measures of association between Bell’s palsy and higher blood pressure during late pregnancy.

Exclusion criteria

1. Pregnant women with congenital facial palsy, cerebrovascular disease and a history of facial trauma.

2. Case reports, case series, reports, editorials, book chapters, conference proceedings, commentaries, letters and animal studies.

3. Studies that have included women with prior hypertensive disorders before pregnancy.

Only the latest or the most informative study will be included as multiple studies evaluate the same population.

Data collection process

Two reviewers will independently extract data using a standardised data collection form, including the following data: (1) first author’s name; (2) year of publication; (3) country; (4) study region; (5) study design; (6) characteristics of the study population (sample size, maternal age, gravida/para/abortus system, fetus number); (7) exposures: the type of gestational hypertension and the median (IQR) systolic blood pressure, diastolic blood pressure; (8) time of occurrence of Bell’s palsy (the late second trimester, the third trimester or post partum); (9) route of delivery (caesarean section or normal labour). A third reviewer (SZ) will be consulted to resolve any disagreement throughout the data extraction.

Risk of bias assessment

Two reviewers (Y-NL and Z-WX) will independently evaluate the risk of bias and the quality of the studies included in this meta-analysis. Case-control and cohort studies will be assessed using the Newcastle-Ottawa Scale based on three categories: selected cases, comparability of groups, and assessment of outcomes.¹⁸

Data synthesis and analysis

The results for each condition of gestational hypertension will be presented separately. We will summarise by using the narrative approach and tables to describe the characteristics of the included studies. If the data permit and the study design, methods, exposure and outcomes are similar enough, the overall pooled estimates for the association between Bell’s palsy and gestational hypertension will be calculated in the meta-analysis. Study heterogeneity will be assessed using the I² statistic.¹⁹ According to the Cochrane Handbook criteria, I²≤50% was considered low heterogeneity, and a fixed-effects model will be used in the analysis. Otherwise, the heterogeneity will be considered high if I²>50% and a random-effects model will be used. We will investigate sources of heterogeneity by using meta-regression analysis and subgroup analysis when substantial heterogeneity is detected. If a study is eligible for inclusion in the systematic review but does not provide adequate data for inclusion in the meta-analysis, we will also conduct a systematic review with descriptive analysis. Summary effect measures are calculated based on OR and 95% CI. All analyses will be performed in the statistical software R V.4.2.0 (R Foundation for Statistical Company, Vienna, Austria). If appropriate, and if such data can be retrieved from the manuscripts, subgroup analysis will be performed according to the age of pregnant women (≤35 years old, >35 years old), parity (primigravida, primipara) and fetus number (singleton or multiple-gestation pregnancy).

Patient and public involvement

The study design protocol does not involve patient recruitment or public involvement.

Ethics and dissemination

This review will be based on published literature, and thus there is no requirement for ethics approval. The results of this study will aid in the knowledge of the relationship between Bell's palsy and hypertensive disorders during pregnancy or the puerperium. The results of this systematic review will be shared through publication in a peer-reviewed journal with good visibility for the field of obstetrics and presentations at academic conferences.

Ethics statements

Patient consent for publication

Not applicable.