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March 2023, Volume 73, Issue 3

Systematic Review

Treatment of periodontal disease in pregnancy for the prevention of adverse pregnancy outcomes: a systematic review of systematic reviews

Najia Sajjad Khan  ( Department of Community Dentistry, Ayub Medical College, Abbottabad, Pakistan )
Rebecca Craven  ( Department of Dental Public Health, The University of Manchester, United Kingdom )
Ayesha Rafiq  ( Department of Medical Education, Ayub Medical College, Abbottabad, Pakistan. )
Anam Rafiq  ( Department of Oral and Maxillofacial Surgery, Ayub Medical College, Abbottabad, Pakistan )

Abstract

Objective: To assess the systematic reviews and meta-analyses investigating whether or not periodontal treatment in pregnancy was effective in reducing the adverse pregnancy outcomes of preterm birth, low birth weight, preterm low birth weight, stillbirth, foetal growth restriction, and pre-eclampsia.

 

Method: The umbrella review was conducted on May 30, 2021, and comprised search of electronic databases MEDLINE, EMBASE, Cochrane Database of Systematic Reviews via Ovid and CINAHL via EBSCO for all systematic reviews and meta-analyses, regardless of the publication date, of randomised controlled trials which investigated the effects of periodontal treatment during pregnancy in preventing or reducing the frequency of at least one adverse pregnancy outcome. The selected studies were subjected to quality assessment and narrative synthesis.

 

Results: Of the 110 studies found, 17(15.5%) met the inclusion criteria. Of them, quality assessment was high for 1(5.9%), moderate 14(82.3%), and low 2(11.8%). A total of 8(47%) studies demonstrated an association with low birth weight, 7(41.2%) with preterm birth, 3(17.6%) with preterm low birth weight, 1(5.9%) with small for gestational age, and 1(5.9%) with stillbirth, while no study demonstrated any association with pre-eclampsia.

 

Conclusion: Differential findings provided unclear evidence, but periodontal therapy in pregnancy is still recommended as it causes no harm and reduces the bacterial burden in periodontal disease.

 

Key Words: Periodontal diseases, Infant, Low birth weight, Premature birth, Foetal growth retardation, Stillbirth, Pre-eclampsia.

 

DOI: 10.47391/JPMA.6432

 

Submission completion date: 26-02-2022

 

Acceptance date: 03-09-2022

 

Introduction

 

Preterm birth (PTB), low birth-weight (LBW), preterm low birth-weight (PLBW), foetal growth restriction (FGR), stillbirth and pre-eclampsia are the adverse pregnancy outcomes (APOs) that remain global public health problems even though all of them are preventable1. The definition of LBW, according to the World Health Organisation (WHO), is “a birth weight lesser than 2500 grams or 5.5 pounds”2. WHO has defined PTB as “birth before the completion of 37 weeks”1. FGR comprises intrauterine growth retardation (IUGR) and small for gestational age (SGA). SGA is defined as “weight of infant less than the lower limit of confidence interval often 10th centile of normal curve for weight by pregnancy weeks at term or preterm”3. IUGR is defined as “birth of babies with their weight less than the cut-off point appropriate for their gestational age”3. The definition of stillbirth is “loss of foetus in pregnancies after 20 weeks, or, when the gestational age is unknown, 500g or greater birth weight, corresponding to 22 weeks of gestation in a normally developing foetus”4. The definition of pre-eclampsia is “de-novo hypertension (>140mmHg systolic or >90mmHg diastolic blood pressure on two separate occasions with a difference of 4-6 hours between them) present after 20 weeks of pregnancy combined with proteinuria of >300mg per day with additional organ dysfunction in pregnant women, like involved liver, kidney insufficiency, complications of the haematological and neurological systems, dysfunction in the uterus and placenta or FGR”5. APOs have multiple risk factors, and some of them modifiable in all conditions. These include demographic and social risk factors, like age of mother, multiparity, marital status, twin pregnancies, ethnicity, tobacco and alcohol use, low socioeconomic status and educational level, foetal factors, like chromosomal and genetic abnormalities, medical risk factors before pregnancy, like chronic diseases of hypertension, diabetes, renal disease, and maternal infections, like vaginosis, and risk factors during pregnancy, like vaginal bleeding, gestational diabetes, malnutrition, anaemia, and placental anomalies, like placenta praevia and abruptio placentae2,4,5.

The definition of periodontal disease is, “an infection of the periodontium which supports the teeth and resulting from chronic inflammation of the tissues”2. During the pathogenesis of maternal periodontal disease, bacteria enter the periodontium and produce toxins. These produce a chronic inflammatory response and this triggers recurrent bacteriaemia, which elicits indirectly the hepatic acute phase response. This causes the production of interleukins (ILs), cytokines and prostaglandins. Alternatively, bacteria can directly attack the amnion. All these processes can elicit APOs2.

Over the years, many studies have reported that maternal periodontal disease and APOs are associated with each other and that periodontal therapy, like scaling when carried out in pregnancy, reduced their incidence2,6. But some studies failed to find an association7,8. There are some systematic reviews and meta-analyses showing an association9-11 and there are others showing no association12,13. Systematic reviews have been carried out around the world for improvement of evidence by addressing research gaps and using different methodologies14 to provide high level of evidence allowing decisions to be made regarding healthcare at the levels of the individuals and the populations15 so it is useful to carry out an umbrella review of published systematic reviews and meta-analyses to synthesise the latest evidence. Periodontal disease in pregnancy as a risk factor of APOs is uncertain and whether this is a causal association is unknown. If this association is confirmed one way or the other, it will be an important finding as this risk factor is modifiable and thus preventable2. The current systematic review was planned to assess whether periodontal therapy during pregnancy has an effect in lowering the frequency of APOs.

 

Materials and Methods

 

The umbrella review was conducted on May 30, 2021, and comprised search of electronic databases MEDLINE, EMBASE, Cochrane Database of Systematic Reviews via Ovid and CINAHL via EBSCO for all systematic reviews and meta-analyses in English language, regardless of the publication date, of randomised controlled trials (RCTs) which investigated the effects of periodontal treatment during pregnancy in terms of preventing or reducing the frequency of at least one APO. The review was carried out in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 6.216 and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement17, using the participants, interventions, comparisons and outcomes (PICO) format17.

 

Types of studies: All systematic reviews and meta-analyses of RCTs which were published that compared periodontal therapy in pregnancy with no therapy, control therapy or alternative therapy in pregnancy were considered.

 

Types of subjects: Pregnant women considered to have periodontal disease (gingivitis or periodontitis) after dental examination. There was no limit on race, age, pre-existing health problems or study setting.

 

Types of interventions and comparisons: Therapy in pregnancy for periodontal disease, performed by a dental hygienist or a dentist, which included mechanical debridement like scaling and root planning, polishing, debridement or surgery, either alone or with oral hygiene education, oral antiseptics, topical or systemic antimicrobial treatment compared with either no therapy, alternative therapy or placebo.

 

Outcomes: APOs comprising LBW, PTB, PLBW, FGR, stillbirth and pre-eclampsia, using their standard definitions2-5.

 

Search Methods: The four electronic databases were searched after the development of a search strategy comprising exploration of key words and the identification of related terms by controlled vocabulary and free text. The key words included were Dental Prophylaxis/, Oral Prophylaxis, Dental Scaling/, Dental Polishing/, periodontal disease interventions, Periodontal disease treatment$, periodontal therap$, periodontal instructions, periodontal health education, oral health education, dental health education, oral hygiene instructions, adverse pregnancy outcomes, adverse obstetric outcomes, Infant, Low Birth Weight, preterm low birth weight, Premature Birth/, Infant, Premature/, preterm lab$, preterm birth, Foetal Growth Retardation/, foetal growth restriction, intrauterine growth retardation, Infant, Small for Gestational Age/, constitutionally small, Perinatal Death/, abortions, Stillbirth/, Pre-Eclampsia/, preeclampsia, and combinations of these terms. The formulation of the search strategy was done under the guidance of the University of Manchester Library staff and this ensured robustness and adequacy. The reference lists of the related articles were searched for relevant articles for the identification of studies that may have been missed during the original electronic database search.

 

Data Collection: All systematic reviews and meta-analyses of RCTs which investigated the effects of periodontal treatment during pregnancy in preventing or reducing the frequency of at least one out of the given APOs were included. Studies in which relevant APOs were not reported and periodontal disease did not occur in pregnancy were excluded.

Reports of studies identified from the search of the literature according to the strategy were assessed according to the inclusion criteria. The identification of the titles and abstracts from the literature search was screened independently by two reviewers. Titles and abstracts were examined and where further clarity was required, the full text of the report was sought before including or excluding the study in question.

All identified and included studies were compared for details like names of authors, intervention details, setting, participants’ number, and duration and date of study to make sure that duplicates were eliminated. All data collection procedures were performed independently by the first two reviewers. Disagreements, if any, were resolved by discussion with the third and fourth reviewers.

 

Data Extraction and Management: A data-collection tool was developed using guidance from the Cochrane Handbook to ensure standardisation16. The tool included details of the study setting and design, participant number, population descriptors, intervention types, all outcome measures and the original authors’ conclusions. Data extraction was done independently by the reviewers and duplicated into data extraction forms and these were compared with the original papers to check for discrepancies, and clarifications were made accordingly.

 

Assessment of risk of bias: Assessment of the internal validity of the included studies was done using A Measurement Tool to Assess systematic Reviews 2 (AMSTAR 2)18. Assessment of all the studies meeting the inclusion criteria was done independently by the first two reviewers for the risk of bias with input from other two reviewers. The tool used a set of questions regarding 16 domains and an evaluative approach was used to make an assessment of the critical areas of potential bias. The answers for these questions were ‘Yes’, ‘Partial Yes’ or ‘No’ and then the rating was given as high, moderate, low or critically low.

 

Data synthesis and analysis: As measures of treatment effect in the included meta-analyses, the odds ratio (OR) and risk ratio (RR) were used for data on dichotomous outcomes, and mean difference or standardised mean difference were used for continuous outcomes. Various measures were appropriate as there was variability in design and outcomes in different studies. Extracted data facilitated the description of methodological heterogeneity and clinical heterogeneity. A narrative discussion was generated without conducting a meta-analysis.

 

Results

 

Of the 110 studies found, 17(15.5%) met the inclusion criteria9-13,19-30 (Figure).

 

 

All the 17(100%) studies were systematic reviews of RCTs (Table 1),

 

 

 and 4(23.5%) of them were without meta-analyses11,12,20,29. Approval from relevant ethics review committees had been taken in each RCT reviewed.

 

Participants: All samples related to pregnant women with periodontal disease, and their numbers ranged from 299 to 8,761, and the RCTs analysed in systematic reviews ranged from 1-20.

 

Interventions and comparisons: Interventions of periodontal therapy included non-surgical and surgical treatment with oral health education and antimicrobial therapies. In 2(11.8%) studies11,25 it was not explicitly mentioned what interventions were used, while in 7(41.2%) studies there was no treatment10,12,13, 19, 23, 24,29 (Table 2).

 

 

Outcomes: LBW and PTB were assessed in all the 17(100%) studies; PLBW 5(29.4%) studies10-12,26,29 ; FGR 3(17.6%)9, 10,21 with type SGA.; stillbirth 6(35/3%)9,10,13,24,28,30 ; and pre-eclampsia 3(17.6%)9,10,19 (Table 3).

 

 

LBW: A total of 8(47%) studies demonstrated an association with LBW9-12,23,24,29,30. Besides, 1(5.9%) study21 used chlorhexidine as intervention and it reduced LBW.

 

PTB: Of the total, 7(41.2%) studies reported a significant association of periodontal therapy with PTB,10,12,19,23,24,29,30 while 1(5.9%) study had unclear evidence in this regard11 (5.9%).  The remaining 9(52.9%) studies reported no such association9,13,20-22,25-28. One (5.9%) study21 used chlorhexidine as intervention and it reduced PTB.

 

PLBW: There were 3(17.6%) studies with a significant association between periodontal therapy and PLBW.

 

SGA: With regards to SGA, 1(5.9%) study showed a significant association between periodontal therapy and a greater mean gestational age at delivery21. The study used chlorhexidine as an intervention and it was associated with a greater mean gestational age at delivery21.

 

Stillbirth: Among the studies, 1(5.9%) reported a significant association of  periodontal therapy with stillbirth10. Besides, 1(5.9%) study had unclear evidence9.

 

Pre-eclampsia: No study demonstrated any significant association with pre-eclampsia; 1(5.9%)19 included the outcome but reported no studies on the issue; and1(5/9%) study has unclear evidence9.

 

Risk of bias: Of the total, quality assessment was high for 1(5.9%), moderate 14(82.3%), and low 2(11.8%) (Table 4).

 

 

Discussion

 

The current umbrella review gathered evidence that was collected from systematic reviews with or without meta-analyses for RCTs that had assessed the effect of periodontal therapy in pregnancy on the frequency of the included APOs. Different associations were found which varied according to the types of APOs included and their definitions, number of included studies, statistical analyses type and reported results from the included RCTs. Mostly a moderate or low positive or no association was found for the included APOs, and, for stillbirth, SGA and pre-eclampsia, the number of studies assessed was too low to allow proper assessment of the association. A meta-analysis was not done due to the high heterogeneity found in the studies which were included. This review confirms and increases the knowledge of the APOs found in various systematic reviews and meta-analyses, and the included RCTs whose findings are debatable because of the various methodological problems present.

A total of 8 studies9-12,23,24,29,30 (47.1%) showed an association for LBW, this was similar to another systematic review by Scannapieco et al.,31. A total of 9 studies13,19-22, 25-28 (52.9%) showed no association for LBW, which was similar to 2 other systematic reviews32,33. A total of 7 studies10,12,19,23,24,29,30 (41.2%) showed an association for PTB, which  was similar to 2 other systematic reviews31,34. A total of 9 studies9,13,20-22,25-28 (52.9%) showed no association for PTB, which was similar to 2 other systematic reviews32,33. One study11 showed unclear evidence. A total of 3 studies11,12,29 showed an association for PLBW, which was similar to a systematic review32. A total of 2 studies10,26 showed no association for PLBW, which was similar to a systematic review.33 One study21 (33.3%) showed an association for SGA. A total of 2 studies9,10 (66.7%) showed no association for SGA, this was similar to a systematic review by Xiong et al.,32. In one study21, chlorhexidine increased mean gestational age at delivery. One study10 (20%) showed an association for stillbirth. A total of 4 studies13,24,28,30 (66.7%) showed no association for stillbirth, this was similar to a systematic review by Xiong et al.,32. One study9 (16.7%) showed unclear evidence. One study10 (50%) showed no association for pre-eclampsia, this was similar to 2 other systematic reviews5,32. One study10 (50%) showed unclear evidence. No study (0%) showed an association for pre-eclampsia and this is unlike a systematic review by Matevosyan et al.,34.

Overall differential findings were reported and a definitive conclusion could not be drawn whether the association between periodontal therapy and included APOs was causal or not. This could be explained by the numerous known or unknown risk factors of APOs which could not be controlled and these could be confounding the results. This was similar to 2 umbrella reviews14,15. An umbrella review by Lavigne and Forrest35 showed that there was no association.

According to the AMSTAR 218, quality rating was considered ‘high in only 1 study9 which was the only Cochrane review, low in 2 studies11,29  and moderate in the rest of the 14 studies. There was also varying study quality in included RCTs, with many having high levels of heterogeneity. Often low-quality studies with high heterogeneity showed an effect which was beneficial, hence, overestimating the effect of the treatment. The high-quality studies often showed an unclear treatment effect. Among the included studies, 79,10,13,22,23,25,28 accounted for publication bias.

The included reviews had various methodological and conceptual knowledge gaps which need to be clarified. These include controlling for the numerous confounders, different definitions of periodontal disease and its measurement, different statistical analyses used and different methodologies employed, different definitions of the APOs included, different types of periodontal therapy, its frequency and timing in pregnancy, and the different health professionals delivering it, and the periodontal examiners in the included RCTs. Sometimes there was a positive association of APOs only in high-risk pregnancies. Other problems included lack of assessment of treatment effectiveness. Often, individuals both at high and low risks of APOs were combined in a single study. In the case of stillbirth, 2 studies9,10 reported the outcome of perinatal mortality which had a different definition from stillbirth specifically, making comparison difficult.

The strengths of the current umbrella review is that it has provided the highest form of evidence in evidence-based medicine (EBM). A proper methodological design was used and followed strictly. Four databases were searched, which is twice as many as the minimum two databases recommended by AMSTAR 2.0. The databases searched were appropriate for the research question. There was no limitation on the date and country of publication. Reference lists of the included studies were searched. A standardised data collection tool was used to ensure systematic and appropriate data extraction. The AMSTAR 218 quality assessment tool was used which is designed specifically to appraise the quality of systematic reviews.

The review also has its limitations. Only papers published in the English language were included. No specialists of the subject were consulted nor was grey literature searched. A list of excluded studies is not provided. All the systematic reviews and meta-analyses reviewed included different number of RCTs with different statistical analyses and varying methodological quality. The included studies demonstrated considerable heterogeneity which made it impossible to run meta-analysis.

Pregnant women need a multidisciplinary approach with dentists and periodontists working with gynaecologists and obstetricians, general practitioners and other health professionals14.

More RCTs, systematic reviews and meta-analyses should be carried out in multiple geographical locations using robust methodologies that may minimise many of the methodological problems currently faced.

 

Conclusion

 

The effect of periodontal therapy carried out in pregnant women on the frequency of APOs, like LBW, PTB, PLBW, SGA, stillbirth and pre-eclampsia, revealed differential findings which showed unclear evidence as to whether it was effective or not in reducing the APOs significantly. There were many methodological problems to explain the findings.

 

Disclaimer: None.

 

Conflict of Interest: None.

 

Source of Funding: None.

 

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