Most of the women appreciated maternity care providers who were helpful, sensitive and responsive to their needs, especially when they had no family and relatives around to support them. Women were impressed by the way maternity care providers made them feel cared for, particularly when they followed up to make sure women did not miss their appointments.

A few women thought that while caring for women with FGM was not a common experience for Australian maternity care providers, women expected providers to know how to deal with FGM and how to communicate with women. This woman said:

... *it is not like that the doctors and midwives in Australia come across a circumcised woman every day, you know. And I don't blame them if they are surprised or ask you millions of questions.* (W13)

Several women were worried about the care they might receive because they did not think maternity care providers were adequately prepared to manage FGM as this woman explained:

*The medical sta*ff *need to understand this issue [FGM] and be knowledgeable about it and if they don't have hands-on experience and skills please do not touch us and make our situation worse. You need to feel safe knowing that they get training before coming to women with FGM.* (W23)

The women acknowledged that developing trust with a maternity care provider was directly associated with the provider's competence. Some felt anxious and lost confidence in the ability of maternity care providers to deliver good care when they saw that their care providers were surprised or shocked when they encountered FGM. One woman in a focus group said:

*If these midwives and doctors know where to cut (de-infibulation), how to cut and when to cut it will be so helpful for us and for them because we will not have a problem and they will be relaxed and confident in what they do. Now, as soon as they see us they are shaking* ... *Oh my God. They can get advice from doctors and midwives who worked in our country and have real experience of treatment of women with FGM.* (FGD3)

### *3.2. Desiring the Best in Maternity Services (Dreaming)*

Women expressed their vision for the best maternity care in the future, including how they would wish to be treated within the healthcare system. They described the need for equality and for FGM-affected women to be treated the same way as other women. This included a desire for personalised care to be delivered by a provider from a similar cultural background with services

tailored to the needs of the individual woman. In practical terms, women described how individualised care should mean the provision of support services for women following de-infibulation.

Women believed that each pregnancy is an individual experience and expressed a clear understanding of the need for services to facilitate informed choice and shared decision making in a way that involves women with FGM in their own care. They wanted maternity care providers to listen to each woman and adjust care to suit her individual needs, rather than following the same course for every woman. One woman said:

*They need to listen to women as they know their body better. Not everything is going to be according to the recipe in the book. They have to look at each individual pregnancy separately.*

Women wanted to be treated in the same way as other women without being labelled as different while accessing Australian maternity services. They also wanted to have access to appropriate mental health support that took into consideration their special circumstances due to their FGM, for example:

*If a woman has undergone FGM they need to look after her even after birth and even if there is not any visible harm there is always a change and she needs that emotional support.* (W20)

Many women struggled with their body image and the emotional impact of de-infibulation, and some wished to see their bodies the way they were used to seeing it since childhood (infibulated). This was exacerbated by the fact that legislation in the state did not provide the option of re-infibulation. They perceived a reluctance of health staff to consider any form of reconstruction of the vulval or perineal area and attributed this to laws prohibiting re-infibulation. Women wanted reconstructive surgery to be part of the services offered to them. Most believed that their de-infibulation had been done 'badly' and their body would be 'in better shape' if they were re-infibulated after birth. They desired varying degrees of re-infibulation and used the term 'closed-back' when describing reconstructive surgery. This comment captures such feelings:

*After they open you during delivery I wish there is someone who stitches it very very nicely so it doesn't look very open.* (FGD1)

Most women felt embarrassed and uncomfortable with their bodies and described their vulva as 'ugly', 'too open', 'not in good shape', 'hanging skin', and 'horrible'. Some women chose to undergo a caesarean section to avoid de-infibulation or they travelled back to their home country to be re-infibulated as this woman did:

... *I went overseas and closed it by a midwife in my country.  Some wished that their FGM was not considered as a barrier to undergoing normal labour and birth and questioned interventions such as caesarean section. Several women stated, 'We had our baby normally and easier in our country; why not here'.

Some women felt they were vulnerable, disempowered and dominated by maternity care providers and these providers took control of the situation. Some agreed to let their family members make decisions on their behalf, while others expressed their strong desire to be involved in a collaborative way with maternity care providers. Culture, personal attitudes, and emergencies were also identified by most women as factors influencing the degree to which they could be involved in decision making. For example:

*My husband and mother in law made the decision for me. If it was up to me I would have chosen a caesar straightaway. I did not want all that pain and trauma, but midwife went with my husband and mother in law's decision without listening to me.* (FGD1)

Many women perceived that their lack of health literacy and knowledge about access to certain options or health services led to their exclusion from decision making. One woman explained:

*Sometimes you are in a position where you have to follow whatever they say. Maybe because our knowledge is limited and the language also is a big, big problem.* (W18)

### *3.3. Planning Together for Improved Maternity Services (Designing)*

The 'design' phase of AI invited women, individually or as part of a group, to develop a plan for what they need to achieve their dream for quality care.

In designing future maternity services, women discussed the need for education initiatives that enabled maternity care providers to provide emotional support, promote cultural safety and communicate in ways that are appropriate for supporting women with FGM. The need for training to involve women themselves to improve provider understanding of and familiarity with the cultural beliefs behind the practice of FGM was highlighted, as these women explained:

*If I am a midwife I make you feel good and I need to understand what you believe in so I can understand if you see FGM as a good thing or bad thing. Then I can talk to you and guide you accordingly* ... *first you need to get a sense of what women believe in, otherwise they may not disclose anything.* (W12)

Women also noted that, while maternity care providers need to be respectful and integrate the cultural aspects into their services, they also need to be mindful of harmful cultural practices that may place women at risk. For example, in some cultures, women do not use direct communication to explain their problems related to childbirth, maternity care or FGM. Many women mentioned that they avoided disclosing their FGM as they thought this was culturally inappropriate, as explained here:

*I was shy and hide my FGM until birth and I am sure many other would do that. In our culture women won't talk about it believe me or not. There is shame and stigma with those topics'.* (W23)

Midwifery continuity of care was one of the models of care or services most appreciated by women who received it. Women understood midwifery continuity of care as being cared for by a known midwife over the entire period of pregnancy and childbirth and after birth. Being with the same midwife and building a relationship based on mutual trust and understanding was perceived to improve women's sense of safety and confidence and increase their involvement in their care. Most women, however, did not have access to this model of care. There were a few women who received midwifery continuity of care during pregnancy, but during labour and birth, their known midwives were not present. They expressed feelings of anxiety and distress with being cared for during labour and birth by midwives they had not met before. Women suggested that maternity services should be designed to enable all women to have access to such a model of care, for example:

*It is very important for women because we want to trust someone and by changing midwives and doctors we will be lost. I will also develop my confidence in her competence and make sure she can manage my birth and I am in safe hands. That's a huge support for me knowing that I am safe and someone knows my issues and concerns.* (W17)

Women viewed high-quality maternity care in terms of the way that maternity care providers had behaved towards them. Considering the sensitivity of a topic such as FGM, the women believed positive and effective communication was a key component of maintaining a sense of connection, trust, and collaboration with health providers. For example, they wanted to be heard, touched and welcomed. Many women indicated that building trust happened over time as they got to know their maternity care providers through their direct interactions. As this woman explains, this was especially important in addressing the embarrassment that many women felt because of their FGM:

*You know little by little each time after I started to visit the doctors and midwives and they didn't make me feel embarrassed [because of FGM] and they asked me so many questions when I went to them. And the way they talked to me was so good. You know, you feel so good when someone listens to you. They were not in a rush to get to the next patient and kick me out of their o*ffi*ce. They spend time with you and do what they need to do while they kept privacy.* (W13)

Women wanted to receive emotional support to address their trauma including dealing with health issues related to FGM.

*Sometimes you just want someone to talk to and ask for nothing else, just someone to ask you what your feelings after birth are or how you are because it is a hard time.* ... *I want a midwife or nurse to provide care for me beyond giving medicines, I want them to talk to me and support me emotionally and mentally.* (W17)

Many women felt that there was no transparent, clear, and mutual communication between them and their maternity care providers. As a result, women were often suspicious of the maternity care services they received and were not always willing to accept advice from maternity providers as illustrated with the following quote:

*Sometimes they don't even talk about FGM with us and just write everything down and say all is good without giving us the details. I think it is mostly because they don't know anything about FGM and they just look at you and they have no idea.* (W17)

### *3.4. Improving and Sustaining Maternity Services (Developing*/*Deploying)*

The final theme reflected strategies that women regarded as useful to support their plans to improve maternity services. The women's suggestions represented three levels of action: mobilising and enabling communities, strengthening maternity care systems and increasing government support.

Women believed that communities need to be mobilised to create a supportive environment in which pregnant women and new mothers affected by FGM can feel safe and healthy. Advocacy and campaigns for policy, professional practice, and at a community level were considered critical in creating a supportive environment to improve health outcomes for women in the long term. Raising community awareness, through formal and informal education, campaigns in the community and schools, and involving women, men and young people, were considered essential to delivering positive change. One woman said:

*Still many people in the community believe it is a good thing to do on their daughters [FGM].* ... *I will not let my daughter to undergo FGM but we need to remove pressure of the community on families. If no one wants a girl without FGM then everybody forced to do it. We need to end that by educating community and change this culture.* (W22)

Women believed the practice of FGM was continuing in their communities, even in Australia, and emphasised the need for a reporting system at the community level. Women stated that the success of community-based interventions, such as education and media campaigns, depends upon the involvement of all members of the community including religious and community leaders in the planning and implementation processes of change. Women emphasised the central role of families in bringing a sustainable change to stop a culture such as FGM as explained here:

*Change is dependent on families. In my family, I have already talked to my kids about the stu*ff *like FGM and the even bigger impact of it on society. I think that's how we will spread the word and stop it, otherwise it is never going to be stopped. Now people believe in this society that talking about this issue is wrong or Haram [prohibited by religion]. I don't care; I will talk to my children because I don't want them to grow up blindly.* (W18)

Men were regarded as important actors of change, but women thought that they lacked knowledge about the physical and mental health consequence of FGM. Women felt that men believe that FGM is women's business and that their views on cultural obligation enabled the continuation of FGM. The women, therefore, perceived that men's involvement as a crucial part of the solution to end this practice but it might be very challenging as men are not interested in taking part in such a movement. An example such as this was given:

*At the moment most of the trainings are for women. We need men to talk to men so we can engage them otherwise you cannot force them to sit in a class. You need to train more men to open up and talk about this issue with other men in the community and engage them at the same level as women. Men are still looking at it as a good thing.* (W15)

Women described feeling empowered when they shared their stories and regarded these as an important resource for mutual support and to educate the community and challenge cultural beliefs about FGM. Women also mentioned that they feared being socially ostracised by their families and communities if they expressed dissenting views. This woman explained:

... *We need to create an environment where people talk about it. You know it is very hard to disclose such issues at community level, as it is a very private matter. I guess if we bring up stories and how women are su*ff*ering this would be e*ff*ective to change this culture in the future. Imagine you're living for someone else's pleasure and you're getting none.* (W13)

Women considered government support as a cross-cutting issue linked to all future actions and approaches. Women used the word government to mean all high-level decisions, policy and funding at local, state and territory and federal levels. They wanted resources for improving the health of affected women, introducing FGM as a topic in the school curriculum and making meaningful linkages with communities. They believed such strategies would ultimately lead to the improvement of the health of women with FGM and society as a whole.

*They [policy makers] need to identify women with FGM as a priority at policy level and provide them with things they want. We want services which all women deserve* ... *. We are in a developed country and we should have access to standard care from an experienced health provider.* (W21)

Women also spoke of the need for mental health support and counselling services, both at facility and community level, for example:

*Make sure they [women a*ff*ected with FGM] are OK, mentally and physically. Do the follow up afterwards. Education and individualised support not only for women who have undergone FGM but also to train sta*ff *and the community. It goes both ways.* (W16)

Women pointed to cultural taboos that make it challenging to have open discussions about FGM with male members of the family. Several women made suggestions like this:

*Facilitating and funding community training such as workshops for men and women we can raise the awareness. It is also helpful to open the discussion around this issue. At the moment it is not culturally appropriate to even talk about it even in the family.* (W20)

### **4. Discussion**

This research identified the maternity care experiences of women affected by FGM and their views concerning the care they wished to receive in the future and how this might be achieved. Women in this study acknowledged that the maternity care they received had not always been at the level of quality that they desired or had expected. Women reported that being meaningfully involved in their care design and delivery was a crucial strategy for building trust and improving and validating

the quality of maternity services. It has previously been shown that women who are well educated and have adequate information about FGM are more likely to have control over health care, access to shared decision making. Making an informed choice is key to respectful care for women with FGM [41] and they are less likely to perform FGM for their daughter [42]. While most women were motivated to be involved in their care, they struggled with poor communication and a lack of information tailored to their individual needs as reported elsewhere [43,44]. Women wanted to be cared for by skilled and culturally competent providers who treated them as 'special' but also as normal and equal to 'other women'. This has been described by other research where they ensured equality by including Aboriginal and Torres Strait Islander midwives, who can interact holistically and provide culturally sensitive services [45]. Finally, women described the importance of having access to evidence-based models of care such as midwifery continuity of care and available services including, reconstructive surgery, management of trauma, emotional support, psychotherapy services and cultural support.

A conceptual framework (Figure 2) was developed based on the findings of this research that highlights four priority approaches required to achieve quality care for women with FGM: co-production, woman-centred care, equity and equality and evidence-based models of care. These approaches are underpinned by four strategies that facilitate women's engagement and include involvement in developing health information to being an equal partner in decision making and the co-design of maternity services.

**Figure 2.** Conceptual model of quality improvement within maternity services for women with female genital mutilation (FGM).

### *4.1. Co-Design of Health Literacy Interventions*

Women regularly described the need for information that is tailored to their individual needs and noted that support services, such as counselling, were not always accessible due to language and cultural barriers. Some women stated that these services were not available or integrated into maternity care. This is similar to other studies in high-income countries that have found that women affected by FGM do not always receive or understand the information and resources they required or needed because of social isolation, stigma and a lack of health literacy [46]. When women have lower levels of health literacy, they are less prepared to engage and comply with their care regimes or protocols and as a result, do not receive optimum care [47]. Improving the health literacy of women with FGM may change the attitudes of women towards their own FGM and reduce the likelihood of their daughter's being circumcised [48].

Every woman should feel empowered to build her capacity and skills to use health information effectively and make an informed choice [49]. Many women in our study stated that they were not adequately engaged in their health care because of low levels of health literacy, inadequate information and unfamiliarity with their health rights. Again, these findings concur with other studies [50,51] and confirm that women's participation in the process of health information design leads to more satisfying and positive experiences with enhanced health outcomes [52]. Health literacy programs that involve women designing and delivering programs not only build the capacity of women to facilitate the sharing of stories and experiences but also empowers women to support others in their community [53]. Such approaches are likely to be useful for women affected by FGM.

### *4.2. Co-Design of Evidence-Based Models of Care*

Most women in our study reported different types of FGM-related trauma, which affected their overall quality of life. Women expected health care providers to be responsive to their psychological, emotional and socio-cultural needs as found in other studies [54]. The central philosophy that underpins high-quality maternity care does not only involve a focus on physical health but also emotional well-being and includes quality of life issues [55]. Despite the emotional and mental consequences of FGM, most studies are focused on the physical aspects and implications [56,57]. Laio et al. [58] indicated that women affected by FGM are often silent about their emotional problems due to the stigma associated with FGM and have difficulty communicating with health providers. It is difficult for care providers to recognise or determine the level of psychological trauma that may be caused by FGM, but our study highlights the importance of these considerations.

FGM related trauma is important to note because it can negatively impact on childbirth and sexual relationships highlighting the need for individualised trauma-informed interventions for such vulnerable women. FGM related mental health issues such as PTSD, negative body image and feelings of shame and stigma may also affect women's health-seeking behaviour [59]. A trauma-informed model of care may be an approach to providing safe supportive care to women who have been affected by violence to reduce the consequences of trauma in their life [60].

Women should also be involved in the design of such trauma-informed services so that individual needs, views and experiences can be addressed in a collaborative way [61]. Efforts in the area of trauma-informed care currently focus on strengthening health provider's knowledge and skills based on their interactions with consumers, rather than understanding a women's experiences and needs [62,63]. Implementing participatory interventions, however, requires both the health system and community change [64]. Women need to be supported to become empowered to recognise their potential and utilise their capacity in the design and delivery of services [65]. Creating an environment of collaboration and mutual trust by engaging women and acknowledging their values and lived experiences may ensure that women's needs are understood and their views and culture are taken into account in service design, thereby, improving the quality of culturally safe care.

Correa-Velez and Ryan [66] emphasise the need for specific models of maternity care for marginalised and high-risk women, such as women with FGM, that encompass continuity of care plus educational interventions and the delivery of mental health support. Our study indicates that continuity of care can lead to improved interpersonal communication and can boost women's confidence, the collaboration between a woman and her provider and help facilitate women engagement in the process of care design and delivery [67]. Midwifery continuity of care enables health providers to consider the socio-cultural and emotional needs of marginalised women and, therefore, empowers women to achieve positive outcomes [68]. Such care models ensure the continuous assessment and evaluation of women's experiences, opinions and views that can improve the quality of care for marginalised groups [69].

### *4.3. Co-Design Approaches to Shared Decision Making*

The health system must offer women adequate support to enable them to be empowered to communicate, to ask for help and to question their care [60,70]. Patient participation in the process of service design and delivery is often missing as patients are perceived not to have adequate medical and clinical knowledge [71]. A review of the literature found that consumer involvement in the training of health providers ensures that the health system reflects their needs and desires in the design and delivery of services [72]. Collaborative partnerships have been found to have a positive impact on nursing practice by improving communication and shared decision making [73]. Another example from the field of mental health demonstrates the benefits of sharing the experiences and insights of patients through story-telling and using different aspects of personal experience in the development of a mental health assessment tool [74]. There is limited evidence in maternal health research and further research is needed to determine the best approach to engage women and evaluate the impact of their involvement in the co-design of education and training material, guidelines and health service processes.

### *4.4. Co-Design of Health Professional Education and Training*

Women in our study described the need for health providers to receive special training on the cultural aspects of care for women from diverse backgrounds. This would help to address their need for a model of maternity care that integrates a woman's cultural and individual values with excellent communication and referral paths to promote their well-being and safety as described in other research [75]. The involvement of women in teaching health professionals may be a useful strategy to increase the knowledge of clinicians. One study that investigated the outcomes of learning where consumers delivered classes found that nursing students improved their cultural knowledge and understanding of empathic care [76]. The involvement of mental health consumers in the education of nurses also showed improvements in nurses' communication skills and decreased cultural barriers for consumers as well as reduced discrimination [77]. The integration of cultural safety in practice is challenging as it requires the involvement of service users in the co-design of such services and involving a vulnerable population requires a paradigm shift in power differences between service users and health professionals [51]. Future health services need to be co-produced with women to disrupt the inherent power imbalances.

This study is one of the first of its kind in Australia to analyse this group of women's views and experiences of their maternity care. The use of AI as the methodology was unique and enabled women to focus on their positive experiences and come up with solutions for future action and changes within the health system. The study has highlighted the voices of women providing important knowledge to improve the quality of maternity care for marginalised women.

This study included only women who lived in Sydney, which is generally well resourced in terms of services for migrant populations. Therefore, the results may not be generalisable to the other states across Australia and suggested solutions and recommendations might be specific to the local context.

Sampling bias is a possible limitation. Potential women were recruited through chain referral sampling. Therefore, those who decided to participate in this study might be those who had more interest in this subject area, and this might have led the discussion either more positively or negatively.

### **5. Conclusions**

The engagement of individuals and communities is critical to the process of improving the quality of maternity health services and to address the socio-cultural needs of women affected by FGM. Empowering women and raising their awareness of their health care rights can help to engage women as active partners in the design and delivery of health information, models of care approach to shared decision making and health professional education and training which is based on their needs and context.

Further research is needed to explore the replicability of the suggested framework at policy and practice levels. Research is required to establish the feasibility of the co-production of maternity services and how this improves the quality of care and equitable health outcomes for women affected by FGM.

### **Supplementary Materials:** The following are available online at http://www.mdpi.com/1660-4601/17/5/1491/s1.

**Author Contributions:** Conceptualization, S.T., A.J.D. and C.S.E.H.; methodology, S.T. and A.J.D.; software, S.T.; validation, S.T., A.J.D. and C.S.E.H.; formal analysis, S.T.; investigation, S.T.; resources, A.J.D. and C.S.E.H.; data curation, S.T., A.J.D. and C.S.E.H.; writing—original draft preparation, S.T.; writing—review and editing, A.J.D. and C.S.E.H.; supervision, A.J.D. and C.S.E.H.; project administration, S.T. All authors have read and agreed to the published version of the manuscript.

**Acknowledgments:** This research was supported by the Australian Government Research Training Program (RTP). The authors are thankful for the support provided by the Faculty of Health, University of Technology Sydney (UTS). We also thank women who generously shared their perspectives and ideas and this study would not have been possible without them.

**Conflicts of Interest:** The authors declare no conflict of interest.

### **References**

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

International Journal of *Environmental Research and Public Health*

### *Review* **Prevalence of Intimate Partner Violence in Pregnancy: An Umbrella Review**

**Rosario M. Román-Gálvez 1,2, Sandra Martín-Peláez 3,4,\*, Juan Miguel Martínez-Galiano 5,6, Khalid Saeed Khan 3,6 and Aurora Bueno-Cavanillas 3,4,6**

Received: 1 December 2020; Accepted: 13 January 2021; Published: 15 January 2021

**Abstract:** Background: Intimate partner violence (IPV) is a public health concern, especially during pregnancy, and needs to be urgently addressed. In order to establish effective actions for the prevention of IPV during pregnancy, authorities must be aware of the real burden of IPV. This review aimed to summarize the existing evidence about IPV prevalence during pregnancy worldwide. Methods: A review of reviews was carried out. All published systematic reviews and meta-analyses published until October 2020 were identified through PubMed, Scopus, and Web of Science. The main outcome was the IPV prevalence during pregnancy. Results: A total of 12 systematic reviews were included in the review, 5 of them including meta-analysis. The quality of the reviews was variable. Physical IPV during pregnancy showed a wide range (1.6–78%), as did psychological IPV (1.8–67.4%). Conclusions: Available data about IPV prevalence during pregnancy were of low quality and showed high figures for physical and psychological IPV. The existing evidence syntheses do not capture the totality of the worldwide disease burden of IPV in pregnancy.

**Keywords:** intimate partner violence; pregnancy; prevalence; umbrella review

### **1. Introduction**

Intimate partner violence (IPV), defined as physical violence, sexual violence, harassment, and psychological assault (including coercive tactics) by a current or former intimate partner [1], is a public health concern that urgently needs to be addressed. During pregnancy, the woman experiences a situation of special dependence, both physical and emotional. In this period, exposure to violence affects not only the mother but also the fetus, which is at greater risk than in other stages of life [2]. In fact, IPV has been associated with adverse pregnancy outcomes including increased risk of human immunodeficiency virus infection [3], perinatal depression [4], insufficient weight gain during pregnancy [5], uterine rupture, hemorrhage, maternal death [6], prematurity, low birth weight, newborns small for gestational age [7], stillbirth [8], and reduced levels of breastfeeding [9]. At the same time, routine contacts with the health system offer

an excellent detection window to identify it and establish protective measures. Despite this, IPV during pregnancy is a neglected condition, even though it is more common than many maternal health conditions like preeclampsia and gestational diabetes [10].

IPV during pregnancy should be an avoidable global public health problem. However, in order to establish effective actions for the prevention of IPV during pregnancy, such as the performance of systematic screening and diagnosis of IPV in the antenatal visits, authorities must be aware of the real worldwide burden of IPV. However, information about IPV prevalence is not consistent. Whereas some studies indicate higher prevalence of IPV during pregnancy than before [11] or after [12,13] the pregnancy, other studies report a smaller prevalence [14,15]. Furthermore, the prevalence of IPV during pregnancy is reported to vary depending on the definition used [1], the screening strategy [16,17], and the development status of the population studied [10,18]. These factors make comparison between individually reported rates difficult.

This review aims to summarize the existing evidence about IPV prevalence during pregnancy worldwide through a synthesis of systematic reviews and meta-analysis. Prevalence studies provide a snapshot of a situation in a specific context, so it is important to bring together different existing studies for a global understanding. This work analyzes the existing reviews, identifying their strengths and limitations and laying the foundations for future reviews that clarify the situation of IPV during pregnancy in a complete and realistic way.

### **2. Materials and Methods**

This umbrella review was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses [19] and the Aromataris' guidelines for performing umbrella reviews [20].

### *2.1. Inclusion and Exclusion Criteria*

Systematic reviews and meta-analyses including observational studies reporting IVP prevalence suffered by women during pregnancy were considered in this review. The types of IPV were classified as physical, sexual, psychological and any type of IPV. Studies not following a systematic review approach, narrative reviews, and primary studies were excluded. No language restrictions were applied in this review.

### *2.2. Literature Search and Selection of Studies*

Relevant systematic reviews and meta-analyses according to inclusion criteria were identified through systematic searches of the following electronic databases: PubMed, Web of Science and Scopus, CYNAHL, PsycINFO, Social Science Database, and Sociological Abstracts. The full search strings can be found in Table 1. When the search engine used only allowed selecting systematic reviews or meta-analyses, the terms "systematic reviews" OR "meta-analyses" were not included in the search string; otherwise, those terms were included. Studies published from inception until October 2020 were included. Reference lists of identified studies were checked.

**Table 1.** Search strings.

### *2.3. Data Collection and Analysis*

Eligible studies were selected through a multistep approach (elimination of duplicates, title reading, abstract and full-text assessment). Two researchers (S.M.-P. and R.M.R.-G.) independently examined titles and abstracts, evaluating afterwards full texts according to the inclusion criteria described above. Any disagreement between the reviewers was resolved by means of a consensus session with a third reviewer (A.B.-C.). In case of ambiguity in reporting or lack of data, primary authors were contacted for clarification.

### *2.4. Data Extraction and Management*

Data were independently extracted by two researchers (S.M.-P. and R.M.R.-G.), and the following information was considered for each article: (1) first author and year of publication; (2) interval of time covered by the review; (3) countries (of studies included in the systematic review or meta-analysis); (4) number of studies included; (5) study design (of studies included in the systematic review or meta-analysis); (6) sample characteristics; (7) IPV as main outcome; (8) type of IPV investigated; (9) meta-analysis performance; (10) IPV outcome.

### *2.5. Quality Assessment Tools*

The updated AMSTAR 2 version for systematic reviews and meta-analyses was used to evaluate the methodological quality and risk of bias of studies included in the systematic review [21]. The overall final rating of each systematic review was judged as high, moderate, low, or critically low. In case of disagreements, a consensus session with the third reviewer (A.B.-C.) was held.

### **3. Results**

The electronic search initially resulted in 199 citations. A total of 80 studies were excluded after elimination of duplicates. From the 119 remaining, 61 were excluded after title and abstract screening and 58 full-text articles were selected and read. From those, a total of 12 systematic reviews were included in this umbrella review, of which 5 were meta-analyses. The reasons for exclusion were the lack of data about IPV prevalence during pregnancy (20), the use of violence other than IPV or the indistinct report of IPV or domestic violence (10), investigations on populations with a specific risk, supposedly different from the general population (12), and not being a systematic review or meta-analysis (4). The list of the excluded articles is presented in Supplementary Materials Table S1. Figure 1 shows the PRISMA flowchart and the study selection process.

Characteristics of included systematic reviews and meta-analyses are shown in Table 2. Only two reviews included global data [22,23], most of which were limited to a country or a group of countries, mainly from Asia [4,23–28] and Africa [4,26,27,29,30], followed by America [31,32], Europe [32], and Australia [32]. The number of studies included in the reviews giving information about IPV prevalence during pregnancy ranged from 2 [24] to 73 [23].

Most of the studies included in the selected reviews were cross-over studies, in which there was only a single evaluation of the women sometime during pregnancy. Some of the reviews also included cohort studies [4,24,25,30–32]. Reviews included studies giving information about IPV only at pregnancy [22–24, 27,29,30], both during pregnancy or at postpartum [4,30–32], during pregnancy, or having a child 2 years old or younger [25] or at current pregnancy or any pregnancy [26].

Wide differences were also observed regarding the type of IPV violence investigated. Of the selected reviews, nine investigated prevalence of physical violence [4,22,24–28,30,31], nine psychological violence [4, 22,24–28,30,31], ten sexual violence [4,22–28,30,31], and three any type of violence [26,29,32]. From the selected studies, four did not report IPV pregnancy during pregnancy as main outcome [24–26,32]. Five studies showed a summarized estimate of IPV during pregnancy [23,24,28–30]. In most of the reviews ranges of IPV prevalence are given [4,22,24,26,27,31,32].

**Figure 1.** PRISMA flowchart of the study selection process.

From the reviews included in the study, many showed data about any IPV prevalence worldwide. The data about prevalence of any kind of IPV during pregnancy were obtained from different countries [26,29,32].

The highest range of any IPV prevalence was obtained in Portugal, USA, and Australia [32] (15.4–40%), followed by Ethiopia [29] (26.1% (95% CI: 20–32.3)) and countries from the Arab League [26] (40.9–44.1%).

Regarding physical IPV during pregnancy, China [28] and Vietnam [25] showed the lowest ranges; (3.6% (95% CI: 1.6–6.2%)) and (3–8.5%) respectively. Higher ranges were found in countries from Latin America [31] (2.5–38.7%), Africa and Asia [4] (2–35%) followed by low- and middle-income countries [27] (5–52.8%), countries from the Arab League [26] (10.4–34.6%) and African countries [30] (22.5–40%), being the widest range the one found in Saudi Arabia [24] (21–78%). James and colleagues [22] showed a prevalence of 13.8% in all over the world.

**2.**CharacteristicsofthestudiesselectedfortheumbrellareviewofreviewsofworldwideprevalenceofIPVin

**Table 2.** *Cont*.

242

NR, not reported; Ph, Physical violence; Ps, Psychological violence; S, Sexual violence. \* Number of studies included in the review related to IPV during pregnancy, when in the review

reports IPV during pregnancy and others.

#### *IJERPH* **2021** , *18*, 707

As for any and physical IPV, China [28] showed the lowest and smallest ranges of psychological IPV prevalence during pregnancy (4.2% (95% CI: 1.8–7.5%)). Higher ranges were found in Vietnam [25] (6–32.5%) and countries from the Arab League [26] (23.4–32.6%), Latin America [31] (13–44%), and African countries [30] (24.8–49%). The widest ranges were found in low- and middle-income countries [27] (17–67.4%) and countries from Asia and Africa [4] (22–65%). James and colleagues [22] showed a prevalence of 28.4% throughout the world.

In general, sexual violence showed lower ranges of prevalence than the other types of IPV violence during pregnancy, being the lowest in China [28] (1.3% (95% CI: 0.6–2.5%)), followed by Vietnam [25] (3.4–10%), countries from the Arab League [26] (5.7–15.0%), low- and middle-income countries [27] (2.8–21%), Africa [30] (2.7–26.5%) and Latin America [31] (3–34.4%). The highest and widest ranges of sexual IPV prevalence during pregnancy were found in countries from Asia and Africa in the study of Halim and colleagues [4] (9–40%). Worldwide, prevalence of sexual IPV during pregnancy remained lower than 18% [22,23].

Quality assessment is reported in Table 3. Although all of the studies used a comprehensive literature search strategy, only two of the selected reviews did not include the components of PICO in their research questions and inclusion criteria [22,24], the reviews described the included studies in adequate detail, with the exception of three studies [22,26,32], and in only three of the reviews [22,25,27], authors did not report any statement about potential sources of conflict of interest. For some other aspects of the AMSTAR2 checklist, the quality remained low. Thus, none of the reviews included an explicit statement that the review methods were established prior to the conduct of the review nor the sources of funding for the studies included. Only one review provided a list of excluded studies and justified the exclusions [28]. Only three of the reviews explained their selection of the study design for inclusion in the review [24–26]. Half of the reviews performed study selection in duplicate [4,23–26,28], whereas only three did not perform data extraction in duplicate [4,22,31]. Half of the studies included did not use a satisfactory technique for assessing the risk of bias in individuals included in the review [22,23,27,29,31,32], and more than half did not account for risk of bias in individual studies when interpreting/discussing the results of the review [22–25,31–33]. Only two of the reviews provided a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review [22,26]. In the reviews where meta-analysis was performed, the authors used appropriate methods for statistical combination of results [23,25,28–30], but in only three of them, the review authors assessed the potential impact of risk of bias in individual studies [25,28,30] and only two [28,29] carried out an adequate investigation of publication bias.

**Table 3.** Evaluation of selected IPV during pregnancy reviews based on AMSTAR 2 guidelines.

\* Each number corresponds with an AMSTAR 2 checklist item as follows: 1. Did the research questions and inclusion criteria for the review include the components of PICO? 2. Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol? 3. Did the review authors explain their selection of the study designs for inclusion in the review? 4. Did the review authors use a comprehensive literature search strategy? 5. Did the review authors perform study selection in duplicate? 6. Did the review authors perform data extraction in duplicate? 7. Did the review authors provide a list of excluded studies and justify the exclusions? 8. Did the review authors describe the included studies in adequate detail? 9. Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review? 9. Did the review authors report on the sources of funding for the studies included in the review? 10. If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results? 11. If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis? 12. Did the review authors account for RoB in individual studies when interpreting/discussing the results of the review? 13. Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review? 14. If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review? 15. Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review? NA, Not applicable.

### **4. Discussion**

The aim of this umbrella review was to provide a summary of the evidence currently available on global IPV prevalence in women during pregnancy. Despite the fact that the selected reviews were recent, they are of low quality as assessed against most of the AMSTAR2 recommendations. There were only two reviews giving worldwide IPV prevalence during pregnancy [22,23], both of them complying with less than half of the AMSTAR2 criteria.

### *4.1. Limitations*

We selected systematic reviews for prevalence of IPV in pregnancy, yet we obtained very diverse data. In the reviews, sometimes the concepts of IPV and domestic violence were mixed together. Most of the included studies were cross-sectional self-report surveys, which may have been associated with inaccurate recall [24,28,31]. They did not always specify the gestational time point of IPV evaluation. It was common to find a mix among studies assessing IPV at any time of pregnancy or even after pregnancy. This is important since data can vary depending on the gestational age when IPV is measured, antenatally or after delivery. One review [4] also included studies that assessed violence for a period that is inclusive of, but not exclusive to, pregnancy.

Some of the included reviews, in spite of being systematic reviews, showed possible bias in studies included for evidence synthesis. They generally failed to adequately address the heterogeneity of results [22,28,32]. Others had a very narrow geographical coverage [24–26,29]. In addition, sample sizes of the included studies were generally small [29–31], and the use of standardized and validated IPV instruments was low. Geographical coverage of the reviews selected was mainly focused on low-income countries, a fact that invites readers to infer that IPV is a problem exclusive of those countries, which is far from the reality [34].

The main strength is that we have conducted an umbrella review following up the PRISMA and Aromataris' guidelines. Our search has been exhaustive, collecting all kind of IPV.

### *4.2. Implications*

Whereas the consequences of IPV during pregnancy on the mother and on the newborn are widely known [3–9], the frequency and types of IPV in that period are not fully characterized. WHO recommendations on antenatal care for a positive pregnancy experience advise considering clinical inquiry about the possibility of IPV at antenatal care visits when assessing conditions that may be caused or complicated by IPV [35]. Other prenatal care guidelines affirm that clinical practitioners should be aware of the possibility of IPV, but do not include any specific recommendation related to the screening [36]. It is well known that IPV is associated with adverse mental health and obstetrical health consequences for the mother, fetus, and child, but women are reluctant to speak about this topic without a previous inquiry [37]. The American College of Obstetricians and Gynecologists guidelines recommend screening for IPV at the first prenatal visit, at least once per trimester, and at the postpartum checkup [38]. However, the overall rate of screening asymptomatic women is distressing [39]. Due to the high prevalence of this serious problem, estimated violence during pregnancy ranges from 15 to 40.5% for any type of violence, figures higher than those previously reported by Perttu et al. [40]; it is vital to have a correct estimation of its magnitude. These evaluations are necessary to underscore the importance of systematic screening: only when health staff are aware of the right prevalence and repercussion of IPV will they be able to cope with the screening barriers and to identify the most vulnerable populations by introducing screening programs in antenatal care.

Isolated prevalence studies may underestimate the true IPV prevalence due to barriers to open disclosure. These barriers could vary in different cultures and religions; e.g., widespread social norms in some regions support husbands' right to physically discipline wives. Abused women often face high social, economic, and legal barriers to divorce, a situation that is made worse by unresponsive law enforcement and health care institutions. In this social context, women are often reluctant to report violence to authorities and may hesitate to disclose violence to survey interviewers. In many societies, women are also reluctant to report violence because they are ashamed of living under this kind of relationship.

Summarizing the figures of IPV prevalence in pregnancy is needed to highlight the public health importance of this problem, with rates in some studies reported to be over 50%. These figures point towards the need of systematic screening in pregnancy. However, the analysis of published IPV reviews showed weaknesses in the research available on this topic. This umbrella review allows us to identify some methodological aspects that should be addressed in future reviews, related to geographic scope, study selection, and bias assessment.

### **5. Conclusions**

Available data about IPV prevalence during pregnancy are of low quality. The existing evidence syntheses do not capture the totality of the disease burden in IPV in pregnancy. Despite there being wide variability in existing prevalence figures, it is worth noting that no less than 1 out of 50, and as many as 1 out of 2 women, could be suffering physical IPV in pregnancy. Psychological IPV violence is reported to be even more frequent in the published reviews. The existing evidence syntheses do not capture the totality of the worldwide disease burden of IPV in pregnancy.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1660-4601/18/2/707/s1, Table S1: List of excluded articles.

**Author Contributions:** R.M.R.-G. and S.M.-P. were responsible for data collection and analysis, data extraction and management, and quality assessment. A.B.-C. resolved any disagreement between R.M.R.-G. and S.M.-P. R.M.R.-G., S.M.-P., K.S.K., A.B.-C., and J.M.M.-G. participated in study design, analysis, and data interpretation. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** K.S.K. is a Distinguished Investigator funded by the Beatriz Galindo (senior modality) Program grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government.

**Conflicts of Interest:** The authors declare no conflict of interest.

### **References**

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

International Journal of *Environmental Research and Public Health*

### *Review* **Relationship Between Prolonged Second Stage of Labor and Short-Term Neonatal Morbidity: A Systematic Review and Meta-Analysis**

### **Nuria Infante-Torres 1, Milagros Molina-Alarcón 2, Angel Arias-Arias 1, Julián Rodríguez-Almagro 3,\* and Antonio Hernández-Martínez <sup>3</sup>**

Received: 2 September 2020; Accepted: 21 October 2020; Published: 23 October 2020

**Abstract:** To evaluate the association between prolonged second stage of labor and the risk of adverse neonatal outcomes with a systematic review and meta-analysis. PubMed, Scopus and EMBASE were searched using the search strategy "Labor Stage, Second" AND (length OR duration OR prolonged OR abnormal OR excessive). Observational studies that examine the relationship between prolonged second stage of labor and neonatal outcomes were selected. Prolonged second stage of labor was defined as 4 h or more in nulliparous women and 3 h or more in multiparous women. The main neonatal outcomes were 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit, neonatal sepsis and neonatal death. Data collection and quality assessment were carried out independently by the three reviewers. Twelve studies were selected including 266,479 women. In nulliparous women, a second stage duration greater than 4 h increased the risk of 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit and neonatal sepsis and intubation. In multiparous women, a second stage of labor greater than 3 h was related to 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit, meconium staining and composite neonatal morbidity. Prolonged second stage of labor increased the risk of 5 min Apgar score <7 and admission to the Neonatal Intensive Care Unit in nulliparous and multiparous women, without increasing the risk of neonatal death. This review demonstrates that prolonged second stage of labor increases the risk of neonatal complications in nulliparous and multiparous women.

**Keywords:** Apgar score; meta-analysis; Neonatal Intensive Care Unit; neonatal morbidity; newborn care; labor stage; second; systematic review

### **1. Introduction**

The second stage of labor is the period of time between full cervical dilatation and birth of the baby, during which the woman has an involuntary urge to bear down, as a result of expulsive uterine contractions [1].

The description of the onset of the second stage of labor in clinical practice is often not precisely known. If complete dilatation is found on vaginal examination, it remains uncertain how long this cervical status has been present [2].

Multiple observational studies [2–4] have observed an increase in maternal complications associated with a prolonged second stage of labor, such as operative vaginal delivery, third-/fourth-degree perineal lacerations, caesarean delivery, urinary retention, postpartum hemorrhage and chorioamnionitis, as well as an increase in neonatal complications like seizures, hypoxic-ischemic encephalopathy, sepsis and increased mortality. However, the criteria these studies used to define the second stage of labor are heterogenous.

Thus, diagnosis and management of prolonged second stage of labor and its complications are difficult and often pose a dilemma to the obstetrician regarding timing and type of intervention [5]. Additionally, evidence on the duration of the second stage of labor is of very low certainty [1] and it is unclear whether there is a point of time from which the risk of perinatal complications increases and at which health professionals should intervene to prevent adverse events [3,6].

Nevertheless, there are professionals involved in childbirth care that try to reduce the duration of the second stage by obstetric interventionism in order to avoid neonatal complications. Paradoxically, these interventions, such as immediate pushing (initiated as soon as complete dilation is identified) [7], instrumental birth [8] or fundal pressure [9], may themselves increase the risk of neonatal morbidity.

In the past, a prolonged second stage of labor had been defined as a period of time that lasted beyond 2 h with epidural analgesia or 1 h without epidural analgesia for multiparous women. For nulliparous women, a prolonged second stage is defined as a period of time that lasted beyond 3 h with epidural analgesia or 2 h without epidural analgesia [10]. Recently, though, the American College of Obstetricians and Gynecologists (ACOG) [11] and the National Institute for Health and Care Excellence (NICE) [12] have allowed longer durations in specific cases. In spite of this, the correct management of the second stage of labor should be individualized according to birth progress, fetal malposition or the use of epidural analgesia [11,12]. For example, the Eunice Kennedy Shriver National Institute of Child Health and Human Development document suggested allowing one additional hour for the use of epidural analgesia. Thus, at least 3 h in multiparous women and 4 h in nulliparous women would be considered to diagnose a prolonged second stage of labor [11].

Thus, our objective was to evaluate the evidence on the association between prolonged second stage of labor (defined as 4 h in nulliparous women and 3 h in multiparous women) and the risk of adverse neonatal outcomes.

### **2. Materials and Methods**

This systematic review with a meta-analysis was done according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) [13,14].

### *2.1. Data Sources and Searches*

The adopted search strategy was: "Labor Stage, Second" (Mesh) AND (length OR duration OR prolonged OR abnormal OR excessive). Studies were identified in three main databases: PubMed [15], Scopus [16] and EMBASE [17], from 1 January 1990 to 1 November 2019. As well as published studies, we included non-published studies which had been included in the conference proceedings of the main scientific associations and indexed in the databases consulted. All languages were included. The search results for each database are provided in detail in Table A1.

All members of the research team had prior training in the methodology of systematic reviews, literature reviews and critical reading. AAA and AHM are also experts in meta-analysis.

Studies were included according to four criteria: (I) duration of second stage of labor greater than 4 h in nulliparous women; (II) duration of second stage of labor greater than 3 h in multiparous women; (III) studies reporting neonatal outcomes in relation to duration of second stage of labor; (IV) studies that stratified results by parity. Reference lists from the selected studies were also examined to locate further studies not identified using the search strategy. Two authors (NIT and AAA) independently performed the literature search and excluded any articles that did not meet the established inclusion criteria. A third author (MMA) was consulted to resolve any disagreements or uncertainty regarding inclusion.

### *2.2. Main Outcomes*

The primary outcomes were 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, neonatal sepsis and neonatal death. All neonatal outcomes examined by the available studies were included in this review. The definitions of some of the variables included in our study are shown in Table 1.

NR: not reported.

### *2.3. Data Extraction and Quality Assessment*

Data collection and quality assessment were carried out independently by the three reviewers (NIT, AHM and JRA). We tried to contact the authors of several studies to provide us with data that did not appear in their manuscripts.

We used the Joanna Briggs Institute Critical Appraisal tools for use in JBI Systematic Reviews to assess the risk of bias in each included study [24]. Eleven domains were assessed to appraise the methodological quality of a study and to determine the extent to which a study had addressed the possibility of bias in its design, conduct and analysis.

### *2.4. Data Synthesis*

For the categorical results, the odds ratio (OR) was used along with its 95% confidence intervals (95% CI). To calculate the OR, either the Mantel–Haenszel fixed-effects or Der Simonian–Laird random-effects models were used, depending on whether there was heterogeneity between the studies. Heterogeneity was assessed using the I<sup>2</sup> and the statistical Cochran's Q tests. I2 values of < 25%, 25–50 and >50% normally correspond to small, medium and large heterogeneity, respectively [14,25,26]. Publication bias was also evaluated using the Egger asymmetry test and funnel plots [14,27]. Statistical significance was defined at the ≤0.05 level.

All calculations were done with the StatsDirect statistical software, version 2.7.9. (Stats Direct Ltd., Cheshire, England) [14].

### **3. Results**

### *3.1. Study Selection*

A total of 1868 studies were selected from the literature search. After removing any duplicated articles, 267 were selected by title and abstract. After applying the inclusion/exclusion criteria, twelve articles were selected for the qualitative and quantitative analyses (meta-analysis) (Figure 1).

**Figure 1.** PRISMA flow diagram of the literature reviewing process.

### *3.2. Study Characteristics*

The description of the studies included in this systematic review are shown in Table 2. The sample included 268,624 women. The selected studies were conducted in Canada [4,18,28], United States [19–21, 29,30], China [31], Sweden [22,32] and Spain [23]. The sample size of these studies ranged from 307 [31] to 121,490 [4]. All studies were restricted to singleton infants with cephalic presentation. Eight of these articles studied nulliparous women [18,20–22,28,30–32], two studied multiparous women [19,23] and two studied both (nulliparous and multiparous women) [4,29]

**2.**Characteristics of the studies analyzed.

**Table**

**Table 2.** *Cont.*

**Table 2.** *Cont.* NC: not calculated, NR: not reported, EA: epidural analgesia, BW: birthweight, WG: weeks gestation, \*: no data on

nulliparous/multiparous.

### *3.3. Study and Data Quality*

The included studies had a low risk of bias, except for three studies that did not identify confounding factors [18,28,31] and four studies that did not include strategies to deal with confounding factors [18,28,30,31] (Table A2).

With regard to the selection of subjects, all studies except one [31] specified inclusion and exclusion criteria, selecting all women (nulliparas and/or multiparas) with singleton cephalic presentation that reached second stage of labor within a specific period of time.

Seven of the studies included in the meta-analysis [4,18,20,21,23,28,32] correctly defined prolonged second stage of labor (in this case, second stage of labor longer than 4 h in nulliparas and longer than 3 h in multiparas). Conversely, only three of them [18,21,28] established the maneuver used once prolonged second stage of labor was diagnosed (instrumental birth, continuing maternal pushing, caesarean, etc.).

As for data and information collection, five studies [4,22,23,30,32] included missing or incomplete data as exclusion criteria, so they were not included in the analysis.

### *3.4. Main Outcomes and Meta-Analysis*

### 3.4.1. Nulliparous Women

### <IP_ADDRESS>. min Apgar score <7

To determine the relation between prolonged second stage of labor in nulliparous women (Table A3) and risk of low 5 min Apgar score (<7), six studies were included (*n* = 116,624) [4,18,28,30–32]. A significant increase in low 5 min Apgar score was observed when the second stage of labor lasted more than 4 h with respect to when the second stage of labor was ≤ 4 h. (OR = 1.65; 95% CI: 1.20–2.27). For this analysis, a random-effects model was used since heterogeneity was observed (Cochran's Q *p*-value = 0.0041; I2 = 71.0) (Figure 2a; Table 3).

### Admission to Neonatal Intensive Care Unit

To assess the risk of admission to the Neonatal Intensive Care Unit, eight studies were employed (n = 156,650) [4,18,20–22,28–30].

The risk significantly increased when the second stage of labor lasted more than 4 h with respect to when the second stage of labor was ≤ 4 h (OR, 1.63; 95%CI 1.44–1.84). For this analysis, a random-effects model was used since medium heterogeneity was observed (Cochran's Q *p*-value = 0.057; I2 = 48.8) (Figure 2B; Table 3).

### Neonatal Sepsis

By combining three studies (*n* = 82,053) [4,20,21], we found that the risk of neonatal sepsis increased when the duration of the second stage of labor was longer than 4 h with respect to when the second stage of labor was ≤ 4 h (OR, 1.57; 95% CI 1.07–2.29). For this analysis, a fixed-effects model was used since no heterogeneity was observed (Cochran's Q *p*-value = 0.7962; I2 = 0.0) (Table 3).

### Neonatal Death

Two studies (*n* = 28,032) [18,21] were employed to determine the relationship between prolonged second stage of labor and risk of neonatal death, and no differences were found (OR, 7.21; 95% CI 0.37–139.71) (Table 3).

### Other Neonatal Outcomes

No significant associations were reported between prolonged second stage in nulliparous women and 1 min Apgar score < 1, 5 min Apgar score ≤ 3, umbilical artery pH < 7, acidosis, meconium-stained amniotic fluid, meconium aspiration, birth depression, minor or major trauma, birth trauma, shoulder dystocia, brachial plexus injury, Erb's palsy, resuscitation at birth, heart compressions, hypoxic ischemic encephalopathy, hypothermia treatment or composite neonatal morbidity. When the results of two studies were combined [20,22], only an increased risk of neonatal intubation in women with a second stage of labor > 4 h was observed (OR, 2.19; 95% CI 1.23–3.90) (Table 3).

### 3.4.2. Multiparous Women

### <IP_ADDRESS>. min Apgar Score < 7

To determine the relation between prolonged second stage of labor in multiparous women (Table A4) and risk of low 5 min Apgar score (< 7), three studies were included (*n* = 72,857) [4,19,23]. A significant increase in low 5 min Apgar score was observed when the second stage of labor lasted more than 3 h with respect to when the second stage of labor was ≤ 3 h (OR, 3.67; 95% CI 2.49–5.43). For this analysis, a fixed-effects model was used since no heterogeneity was observed (Cochran's Q *p*-value = 0.987; I2 = 0.0) (Figure 2C; Table 3).

### Admission to the Neonatal Intensive Care Unit

To assess the risk of admission to the Neonatal Intensive Care Unit, three studies were employed (*n* = 76,692) [4,19,29]. The risk significantly increased when the second stage of labor lasted more than 3 h with respect to when the second stage of labor was ≤ 3 h (OR, 2.41; 95% CI 2.02–2.88). For this analysis, a fixed-effects model was used since no heterogeneity was observed (Cochran's Q *p*-value = 0.417; I2 = 0.0) (Figure 2D; Table 3).

### Neonatal Sepsis

None of the studies that analyzed multiparous women considered this variable when assessing neonatal morbidity in relation to the duration of the second stage of childbirth (Table 3).

### Neonatal Death

None of the studies that analyzed multiparous women considered this variable when assessing neonatal morbidity in relation to the duration of the second stage of childbirth (Table 3).

### Other Neonatal Outcomes

No significant associations were reported between prolonged second stage in multiparous women and umbilical artery pH < 7.0, umbilical artery pH < 7.10, umbilical artery base excess ≥12, meconium aspiration, shoulder dystocia, prolonged neonatal stay, advanced neonatal resuscitation, birth depression, minor or major trauma or any perinatal morbidity. After combining two studies [19,29], only an increase in the risk of meconium staining was observed (OR, 1.29; 95%CI, 1.01–1.66), and an increase in composite neonatal morbidity (OR,1.97; 95% CI, 1.39–2.80) was observed after another two studies were combined [19,23] (Table 3).

### 3.4.3. Publication Bias

We did not observe publication bias for the study in any of the variables studied (Tables A3 and A4).

We can observe a summary of results obtained following meta-analysis of all variables studied in nulliparous and multiparous women in Table 3.

### **4. Discussion**

### *4.1. Main Findings*

Our meta-analysis results suggested that duration of second stage of labor of more than 4 h in nulliparous women increased the risk of low 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, neonatal sepsis and neonatal intubation. In multiparous women, when the second stage of labor was longer than 3 h, the risk of 5 min Apgar score < 7, admission to Neonatal Intensive Care Unit, meconium staining and composite neonatal morbidity increased.

However, a prolonged second stage of labor did not increase the risk of any of the other variables studied, such as umbilical artery pH < 7, birth depression, neonatal death meconium aspiration or shoulder dystocia.

### *4.2. Comparison with Existing Literature*

The literature has very limited data on neonatal outcomes of women with duration of second stage of labor of more than 4 h in nulliparas and of more than 3 h in multiparas. We were only able to locate 12 articles with these durations for this review.

An example of this is a recent systematic review by Gimovksy et al., which evaluated the maternal and fetal morbidities associated with prolonged second stage of labor in nulliparous women with epidurals, in which the authors defined prolonged second stage as greater than three hours [33]. Only two papers were included in this systematic review, and very discordant neonatal outcomes were analyzed, which did not allow the results to be combined in order to establish conclusions that would be useful for decision-making in clinical practice.

Another systematic review studied the influence of prolonged second stage of labor on the risk of adverse maternal and neonatal outcomes from 1980 until 2005 [34]. It did not report associations between prolonged second stage and adverse neonatal outcomes, but most of the studies analyzed in this review defined the prolongation of the second stage as more than 2 h, without differentiating according to parity. In addition, it did not conform to the new recommendations of allowing longer durations.

Only one randomized controlled trial [35] specifically addressed the effect of this change in obstetric practice on maternal and neonatal outcomes. In that trial, a policy of extending the second stage of labor for at least 1 h in nulliparous women with epidural anesthesia with respect to "usual labor" (3 h) decreased the incidence of caesarean birth by more than half compared with the common practice (19.5%, 8 of 41, vs. 43.2%, 16 of 37; RR, 0.45; 95% CI, 0.22–0.93). Maternal or neonatal morbidity were not statistically different between the groups. Unfortunately, the trial was underpowered to detect significant differences in the frequency of adverse maternal or neonatal outcomes between groups because the sample studied was very small (only 78 nulliparous women) (35).

However, Zipori et al. [36] recently published another study comparing maternal and neonatal outcomes over two distinct time periods. In period I, the duration of the second stage of labor was considered prolonged according to ACOG limits, and it was called a "classic labor curve" (10). The "new labor curve" of period II allowed nulliparous and multiparous women to continue the second stage of labor for an additional 1 h before diagnosing second-stage arrest. Primary caesarean deliveries decreased with the new policy of labor management, with a small rise in instrumental deliveries, but it also increased other immediate maternal and neonatal complications, such as higher rate of lower umbilical artery cord pH.

### *4.3. Strengths and Limitations*

One of the strengths of this study is that it is the first systematic review to define prolonged second stage of labor according the most recent recommendations (11), that is, 4 h for nulliparous women and 3 h for multiparous women. Most of the studies had large sample sizes with sufficient numbers of participants in each group to lend power to the findings, and the majority of them used methods to control for potential confounding factors.

Among the limitations of our systematic review is that neonatal outcome measures were discordant in the included studies, meaning it was difficult to combine data to summarize important clinical findings, and that the definition of two variables (admission to NICU and composite neonatal morbidity) differed among included studies. None of the studies considered the pushing duration or pushing techniques employed (delayed pushing or immediate pushing). Finally, since they were observational studies, there is a risk of confounding bias even though many of the studies included techniques to control confounding.

### **5. Conclusions**

In nulliparous women, a prolonged second stage of labor is not related with an increased risk of neonatal death. However, it is related with an increased risk of 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, neonatal sepsis or intubation. In multiparous women, a prolonged second stage of labor is related with an increased risk of 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, meconium staining and composite neonatal morbidity.

These potential risks associated with a prolonged second stage of labor in both nulliparous and multiparous women should serve as an incentive for professionals involved in childbirth care to increase supervision of mothers who exceed these durations.

More studies are needed, especially clinical studies, to guarantee the safety of newborns when the second stage of labor exceeds 4 h in nulliparous women and 3 h in multiparous women.

**Author Contributions:** Conceptualization, N.I.-T. and J.R.-A.; Methodology, M.M.-A. and A.A.-A.; Formal Analysis, A.H.-M. and J.R.-A.; Writing—Original Draft Preparation, N.I.-T. and M.M.-A.; Writing—Review & Editing, N.I.-T. and A.A.-A.; Supervision, J.R.-A. and A.H.-M.; Project Administration, A.H.-M. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.

### **Appendix A**


**Abstract**

Acid suppressive therapy (AST) has been the primary mechanism to provide gastroesophageal reflux disease (GERD) symptomatic relief and prevent complications in many individuals with GERD. Many AST options exist, but proton pump inhibitors (PPIs) have developed popularity in symptomatic relief for refractory GERD patients. To help reduce persistent symptoms, the use of AST therapy optimization is imperative and involves timing doses appropriately and increasing the dose and dosing frequency. Recently, more data has become available regarding the safety profile of AST, specifically PPI use. This data has raised awareness about its potential for toxicity with longterm use. This chapter focuses on the pharmacological management of GERD with a focus on the current updates regarding AST safety and efficacy.

**Keywords:** histamine 2 receptor antagonists, proton pump inhibitors, acid suppressive therapy, antacids, GERD, gastroesophageal reflux disease


**3. Results**

#### *3.1. Baseline Characteristics of the Study Population*

Table 2 shows the baseline characteristics of the study population according to the OBS tertiles in men and women. In men, the T1 group had higher levels of MBP (*p* = 0.001), serum glucose (*p* = 0.008), insulin (*p* < 0.001), total cholesterol (*p* < 0.001), triglyceride (*p* < 0.001), CRP (*p* < 0.001), and total energy intake (*p* < 0.001) and had lower levels of HDL cholesterol (*p* < 0.001).  The proportion of higher education level and household income was significantly higher in the T3 group in both men and women.

**Table 2.** Baseline characteristics of the study population.

\* *p*-value for the comparison of the baseline characteristics among sex-specific tertile groups of oxidative balance scores at the baseline survey. Significance was set at *p* < 0.05. Abbreviations: MBP, mean blood pressure; CRP, C-reactive protein.

Table 3 shows the baseline characteristics of individual components in relation to sex-specific OBS tertile groups. In both men and women, the T3 group had a higher SFA (*p* < 0.001), omega-6 PUFA (*p* < 0.001), total iron (*p* < 0.001), omega-3 PUFA (*p* < 0.001), vitamin C (*p* < 0.001), vitamin E (*p* < 0.001), selenium (*p* < 0.001), and beta-carotene intake (*p* < 0.001). In both men and women, those in the T1 group were more likely to be people with obesity (*p* < 0.001), current drinkers (*p* < 0.001), and current smokers (*p* < 0.001); had abdominal obesity (*p* < 0.001); and had lower physical activity (*p* < 0.001) than other groups.

**Table 3.** Individual components of the score by oxidative balance score tertiles.

\* *p*-value for the comparison of the baseline characteristics among sex-specific tertile groups of oxidative balance score at the baseline survey. Significance was set at *p* < 0.05. Abbreviations: PUFA, poly-unsaturated fatty acid; MET, metabolic equivalent of task.


**3.1. Components affecting coagulation**

Ticks saliva has other strategies besides inhibiting blood coagulation factors, in order to facilitate the feeding. After injury, subendothelial tissue get exposed, activated platelets bind to exposed von Willebrand factor and collagen through its surface receptors and platelets release soluble vasoconstrictor mediators (ADP, serotonin, and thromboxane A2 ). Physiologically, there are three major mechanisms that regulate anticoagulation: TFPI, antithrombin III (ATIII), and protein C/thrombomodulin/activated protein C. Until now, there are no description of tick saliva components interfering with or imitating antithrombin, protein S, protein C, heparin, or thrombomodulin [24]. However, many ticks can inhibit thrombin-induced platelet aggregation. On the other hand, anticoagulant molecules from tick saliva also regulate hemostasis by inhibiting blood coagulation factors (FXa or thrombin) or tenase complexes (FVIIa/ TF and FIXa) and/or platelet aggregation [132].

fibrinogen or other ligands to platelet receptors such as savignygrin from *O. savignyi* [141]. Variabilin is another anti-platelet RGD-containing peptide from *Dermacentor variabilis* [142]. Some inhibitors identified in *I. pacificus* and *I. scapularis*, known as ixodegrins, display some differences with variabilin by having cysteines flanking the RGD motif, and with savignygrin,

Anticoagulants from Hematophagous http://dx.doi.org/10.5772/intechopen.78025 51

Other anti-platelet molecules from ticks were reported: monogrin from *Argas monolakensis* [144], moubatin, a lipocalin derived from *O. moubata* which inhibits collagen-induced platelet aggregation by scavenging thromboxane A2 [139, 140, 144], longicornin, isolated from the salivary gland of *Haemaphysalis longicornis*, which also inhibits collagen-mediated platelet

To target blood coagulation, components from tick saliva have inhibitory activities on the extrinsic tenase complex in blood coagulation [132]. From the studies in *I. scapularis* tick (Acari: Ixodidae) [146], two classes of extrinsic tenase complex inhibitors were identified acting similarly, but not identically, to the physiological inhibitor, tissue factor pathway inhibitor (TFPI) [136]. The first group is represented by ixolaris [147], a 15.7 kDa molecule obtained from the cDNA library of the salivary glands of *I. scapularis* consisting of 140 amino acid residues containing 10 cysteine and two-Kunitz tandem domain which does not bind to FXa active site, in contrast TFPI. It was hypothesized that the second Kunitz domain of ixolaris binds first to FX/FXa (on a heparin binding proexosite/exosite) before binding to the FVIIa-TF complex via the first Kunitz domain. The native inhibitor has a molecular mass of 24 kDa, and both forms are equally effective as anticoagulants. Functionally, the Ixolaris is structurally distinct from human tissue factor pathway inhibitor (TFPI) [146]. The second group is represented by penthalaris [148], a five-Kunitz tandem domain which uses FX or FXa as scaffold to inhibit the FVIIa-TF complex.

One of the main classes of FXa inhibitors characterized from soft tick saliva is the atypical, non-canonical Kunitz-type inhibitors including the tick anticoagulant peptide (TAP), obtained from the *Ornithodoros moubata* tick [9] and FXa-inhibitor (FXaI) from *O. savignyi* tick [149] (Acari: Argasidae). Both inhibitors possess a single Kunitz domain, in contrast to the tandem Kunitz type thrombin inhibitors. Kinetically, both are slow, tight-binding, competitive inhibitors of FXa. The recombinant (rTAP) TAP has a single-chain acidic polypeptide composed of 60 amino acids including 6 cysteine residues, and is a competitive FXa inhibitor highly selective and reversible. Its molecular weight is 6.8 kDa, pI 4.5 and Ki of 0.588 for the native form, and Ki of 0.18 nM for the recombinant form, expressed in *Saccharomyces cerevisiae* [150–152].

Amblyomin-X is a FXa inhibitor identified molecule in the transcriptomics profile of the salivary glands by Expressed Sequence Tags (ESTs) from the hard tick *Amblyomma cajennense* (currently *Amblyomma sculptum*) [153], containing an unique structure with a N-terminal Kunitz-type domain of 60 amino acids and a C-terminal with 49 amino acids. Amblyomin-X is able to inhibit factor Xa, prothrombinase and tenase activities. As FXa inhibitor, Amblyomin-X

which have a non-canonical RGD peptide inserted into a Kunitz fold [127, 143].

aggregation [145].

*3.1.2. Tenase complex inhibitors*

*3.1.3. Factor Xa inhibitors*

Anticoagulants from tick saliva can be classified according with their biochemical characteristics and structure, some of them belonging to the Kunitz-type domain inhibitors and Serpin domain inhibitors [127]. Members of those families can modulate coagulation, inflammation, or vasoconstriction. For example, the Serpin IRS-2 (*I ricinus* Serpin-2) from *I. ricinus* inhibits cathepsin G and chymase, both known as mediators of platelet aggregation and inflammation [133], as well as to mediate vascular permeability [25]. Besides, Kunitz domain inhibitors are widely expressed and characterized as anticoagulants, some of them having just one Kunitz domain being able to inhibit factor Xa [134] or thrombin, such as savigin from *Ornithodoros savignyi* [135].

Depending on the mechanism of action, they can include platelet inhibitors, factor Xa inhibitors and thrombin inhibitors, since they are able to prevent blood clotting and maintain blood incoagulable. Those blood coagulation inhibitors from tick are the major focus of this section.


**Chapter 19 351**

Antioxidants: Natural Antibiotics *by Syed Ali Raza Naqvi, Sana Nadeem, Sana Komal, Syed Ali Asad Naqvi, Muhammad Samee Mubarik, Sajid Yaqub Qureshi, Shahzad Ahmad, Ali Abbas, Muhammad Zahid, Naeem-Ul-Haq Khan, Syed Shujat Raza and Nosheen Aslam*

## **Chapter 20 369**

Diseases Related to Types of Free Radicals *by Narendra Maddu*

#### **Chapter 21 387**

The Effect of Antioxidants on Ischemia-Reperfusion Injury in Flap Surgery *by Mehmet Bozkurt, Melihcan Sezgic, Percin Karakol, Can Uslu and Tevfik Balikci*

**II**

**Section 2**

Arthritis

Stroke

Antioxidants Compounds and Diseases **147**

**Chapter 8 149**

**Chapter 9 173**

**Chapter 10 185**

**Chapter 11 197**

**Chapter 12 219**

**Chapter 13 245**

**Chapter 14 261**

**Chapter 15 277**

**Chapter 16 295**

Condensed Benzimidazoles Are a Novel Scaffold for Antioxidant Agents'

Importance of the Nutrition with Antioxidants in the Treatment of Cancer

Prospects for Using the Natural Antioxidant Compounds in the Obesity

*by Andriy Zagayko, Tatiana Briukhanova, Dmytro Lytkin, Anna Kravchenko*

Potential Antioxidative Effects of Kolaviron on Reproductive Function in

*by Claudine Manirafasha, Omolola Rebecca Oyenihi, Nicole Lisa Brooks,*

Prevention of Oxidative Injury Associated with Thrombolysis for Ischemic

Dietary Antioxidants in the Chemoprevention of Prostate Cancer *by Dwayne Tucker, Melisa Anderson, Fabian Miller, Kurt Vaz,*

*by Vadim A. Kosolapov, Alexander A. Spasov, Vera A. Anisimova*

*by Eva María Molina Trinidad, Marco Antonio Becerril Flores,*

*José Luis Imbert Palafox and Laura Vargas Servín*

Streptozotocin-Induced Diabetic Wistar Rats

*Stefan S. du Plessis and Yapo Guillaume Aboua*

The Role of Endogenous Antioxidants in the Treatment of Experimental

*by Katarina Bauerova, Jarmila Kucharska, Silvester Ponist, Lukas Slovak,*

Antioxidants as a Double-Edged Sword in the Treatment of Cancer

*Mohammad Reza Mahmoudian-Sani and Hedayatollah Shirzad*

*Karol Svik, Vladimir Jakus and Jana Muchova*

*by Melinda Matyas and Gabriela Zaharie*

*by Darryl R. Peterson and Ernest J. Sukowski*

*Lennox Anderson-Jackson and Donovan McGrowder*

Antioxidants at Newborns

Search and Development

*and Olga N. Zhukovskaya*

and Others Damages

*and Victoria Fylymonenko*

Treatment

*by Majid Asadi-Samani, Najmeh Kaffash Farkhad,*

Preface

Damage in biological compounds such as nucleic acid, protein, lipids, etc. occurs when the free radical encounters another molecule and seeks to find another electron to pair its unpaired electron. Free radicals can cause mutations in different biological compounds and lead to various diseases (cancer, cardiovascular disease, aging, etc.). Antioxidants are chemical substances that protect different human cells from free radical damage that can occur from exposure to certain chemicals, smoking, pollution, radiation, and as a by-product of normal metabolism. Most antioxidants come from natural sources, which include wild plants, herbs and spices, fruits and vegetables, aquatic organisms, and microorganisms, and from antioxidant compounds, including vitamins A, C, and E, carotenoids such as beta-carotene, minerals, phenolic compounds, and other natural chemicals with antioxidant properties. There is developing interest in the utilization of natural antioxidants for the preservation of different kinds of foods and in the management of a number of diseases and conditions. The implication of oxidative stress in the etiology and progression of several acute and chronic clinical diseases has led to the suggestion that antioxidant compounds can have health benefits as prophylactic agents. Several studies have consistently shown an inverse association between consumption of natural products (as fruits, vegetables, herbs, algae etc.), the risk of cardiovascular diseases, and certain kinds of cancer. Although the protective effects have been primarily attributed to well-known antioxidants, such as vitamins A, C and E and beta-carotene, plant phenolic compounds may also play a significant role. Moreover, restrictions on the consumption of synthetic antioxidants such as Butylated hydroxyl anisole and Butylated hydroxyl toluene in food further strengthen the concept of using naturally occurring

The aim of this book is to illustrate the definition of oxidative stress and antioxidant in addition to identifying antioxidant sources, mechanisms, its applications in different fields, and the relation between antioxidant compounds and their preventive effect against several diseases such as cancer, cardiovascular disease, inflammation,

The current book will be of interest to students, researchers, and scientists in the

I would like to thank all the contributing authors for their time and great efforts in the careful construction of the chapters and for making this project realizable.

I am grateful to Ms. Sandra Maljavac (Author Service Manager) for her great

efforts, encouragement, and guidance during the preparation of this

compounds as antioxidants.

diabetes, atherosclerosis, etc.

book.

field of biological science and applications.


**Abstract**

Regional anaesthesia is essential for hip arthroplasty programmes and depends on anaesthesiologist's experienced choice. Good analgesia and the avoidance of post-operative nausea and vomiting are prerequisites for early ambulation and patient compliance with post-operative protocols. Regional anaesthesia, both neuraxial and peripheral nerve blocks, is superior to systemic opioid analgesia at all-time points in the first 3 days following surgery and by avoiding opioids, the risks and incidence of opioid analgesia are removed. Safety of drugs for intrathecal injections and complications from spinal anaesthesia continue to be examined and re-examined in order to improve safety of the technique. Prevention of post-operative cognitive dysfunction and early mobilisation is a key part of the management of patients with hip fractures.

**Keywords:** regional anaesthesia, analgesia, hip fracture, immune response, hip replacement