Most prominent difference between African-American and white respondents in perceptions and attitudes about ADHD
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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ADHD constitutes a serious issue in the African-American community. The Center for Disease Control and Prevention lists the African American males as leading other racial groups and gender in the diagnosis of learning and behavioral disorders, incarceration rates, new HIV infections, homicide and poverty. Although the reason for these observations are quite complex and multidimensional, some of the comorbidities found in untreated African Americans patients with ADHD include conduct disorder, oppositional defiant disorder, depression, anxiety disorders, learning disabilities, and alcohol or drug addiction. In addition, even though African American males living in poverty are most likely to be referred to mental health agencies for mental health services, they are the least likely to receive mental health services. In 2006, the number of children in the United States aged between 5 and 7 who were diagnosed with ADHD was 4.5 million. In the last decades the number of children diagnosed with ADHD who are on psychotropic medication continues to rise steadily. However, the impact of this steady rise has been skewed and not evenly distributed by ethnicity, socioeconomic status and gender as minorities (African Americans and Hispanics) are most often diagnosed or misdiagnosed. The incidence of ADHD appears to be similar in African-Americans and White populations. ADHD is diagnosed in 4.1% of all children with the greatest prevalence among Caucasian children (5.1%). However, when the prevalence of ADHD among male children are considered by race, African American children and adolescents are disproportionately diagnosed with ADHD, with an estimated prevalence rate of 5.65%, 4.3% for Hispanics, 3% for Whites; and 1.77% for females of all races. The prevalence of ADHD in African-Americans is most likely similar to that in the general population (3-5%); nevertheless, minority children have lower likelihood of receiving a diagnosis of ADHD and of receiving any treatment. Reasons for this disparity are multifaceted and diverse and have not been fully elucidated. Among some of the identifiable barriers that attempt to explain these disparities are family-driven (parent, patient, and family) and Policy-driven (healthcare system and physician bias) obstacles.
The primary goals of treatment of ADHD are to decrease disruptive behaviors, enhance academic performance, improve interpersonal relationships with peers, family and friends, improve self-esteem, and promote independence. There are difficulties inherent in the diagnosis of ADHD. These include absence of specific diagnostic tests, the lack of specificity of symptoms, inability to observe symptoms that may not be present in an office setting, low rate of concordance in symptom-reporting among various informants (i.e. parents, teachers and parents) and a lack of a standard evaluative process. Although medical professionals may use different diagnostic routes to diagnose ADHD, most agree that the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) is the basis for an appropriate diagnostic process. Others have suggested the use of multiple methods of assessment which are culturally-sensitive and, which involves several people with varying degrees of relationship to the child to be the most effective way to reduce the bias associated with diagnosis. Whaley & Geller observed that the use of informal interviews and methods of assessment seem to increase the bias towards more diagnosis of ADHD towards African Americans. In recent years, following extensive research in this subject by major medical organizations such as the American Academy of Pediatrics (AAP) and the American Academy of Child and Adolescent Psychiatry (AACAP), guidelines have been published to assist physicians in making the diagnosis of ADHD. Efforts must be made to identify these barriers of the diagnosis and treatment of ADHD, awareness among healthcare providers, and the African-American and other Minority communities. The objective of this chapter is to examine the disparities in the diagnosis and treatment of ADHD in the minority groups in America, especially the African-American community, the factors associated with disparities and the impacts of these disparities. The strategies and interventions to address the issue will also be outlined.
Perceptions of ADHD-related symptoms among parents of African American children appear to differ in important ways from those of parents of White children. African American families from low to middle class incomes, compared with Whites, tend to view behavioral and emotional difficulties as problems of and for families, institutions and communities rather than as constituting individual psychopathology. It is not uncommon for African-American parents to perceive many of the symptoms and behaviors associated with ADHD to be variants of normal behavior and not in need of professional intervention. When compared with parents from other ethnic backgrounds, many African-American parents are not well-informed about the symptoms and treatment of ADHD. Indeed, studies suggest that African-American parents may be even more uninformed about ADHD, its causes, diagnosis and treatment than are parents form other ethnic and racial backgrounds. Bussing and colleagues (1998) conducted a study that sought to identify the differences in ADHD knowledge between 224 African-American parents and 262 White parents. They reported that only 69% of African-American parents compared with 95% of White parents had ever heard about ADHD (p<0.01), and that 36% of African-Americans knew “a lot”, “some” or “a little” about ADHD, compared with 70% of White parents (p<0.01). In addition, as reported by African-American parents, only 18% of them received information about ADHD from their physician, compared with 29% of White parents (p<0.01). Equally important, the study found the effects of ethnicity on ADHD familiarity were independent of other covariates, such as socioeconomic status. Furthermore, the lack of knowledge about ADHD among the African-American community has been described as a “vicious cycle” that may be caused when members of this community seek medical advice from other individuals within their own ethnic background who are equally uninformed about ADHD.
ADHD in African-American children is associated with comorbid disruptive behavior; mood and anxiety disorders. However, African-American families may not attribute the symptoms of ADHD to the disorder itself and are less aware than White families about the etiology of ADHD. For example, sugar intake has been reported as a common explanation for the symptoms of ADHD among members of the African-America community. ADHD symptoms in African-Americans are frequently missed or incorrectly diagnosed and comorbid disorders go unattended. African-American parents feel more uneasy than White parents about treating their children with pharmacologic interventions. Dos and other investigators evaluated parental perceptions of stimulant medication for the treatment of ADHD; they demonstrated that significant numbers of non-whites parents (63%) than white parents (29%) thought that counseling was the best choice of treatment, whereas 59% of white parents of white parents preferred medication over counseling compared with 36% of non-white parents. In addition, 16% of non-whites compared with 5% of white parents believed that the use of stimulants would lead to drug abuse. School officials are more likely to assign African-American children to special education classes (which is the only educational resource employed to address many black children with ADHD), although many of the symptoms they display may be resolved with proper treatment that would allow them to remain in their regular classes. Between 1980 and 1990, black children were placed in special education at more than twice the rate of whites.
African-American parents (57%) are more likely to believe that their children’s race or ethnicity and fears of being “labeled” remain one of the important factors preventing acceptance of the diagnosis and treatment of children with ADHD. Many parents fear the perceived social stigma of ADHD diagnosis, and some fear overdiagnosis and misdiagnosis. The stigma of ADHD and lack of information about ADHD were found to be significant barriers to treatment of ADHD among African Americans [Table 1]. In their survey study, Omolara and colleagues (2007) found evidence of racial concerns about the stigma of ADHD diagnosis among African American participants. While some believe that a diagnosis of ADHD “gives children a label for the rest of their lives’, others viewed that medicalization as a form of social control with historical roots.
In addition, pressures from family and friends to refrain from seeking treatment, fear of jeopardizing future employment or ability to serve in the military, concerns that parental skills will be questioned, and fear of the unknown are other factors that have been described by patient and families and these are thought to impact the diagnosis and treatment of ADHD. The African-American population fear of the unknown may be related in part to the consequences of the Tuskegee Experiment, which caused many in the community to lose trust in the field of medical research. However, African American health professionals were even found to be less likely to diagnose ADHD or prescribe stimulant medication treatment due to their social and culturally constructed views of the disorder.
It has also been demonstrated from studies that a substantial proportion of children from all races who are at a high risk for ADHD drop out of care, and that adolescent perceived stigma about ADHD is influential, above and beyond the perspectives of parents.
\n\t\t\t\t | \n\t\t
Most prominent difference between African-American and white respondents in perceptions and attitudes about ADHD
A substantial number of obstacles to the successful diagnosis and successful treatment of ADHD overall are related to limitations in the diagnosis and treatment of ADHD in African-American patients. While some of these barriers are easier to remove, others may prove more difficult. Some of these barriers are race or ethnicity-related, while others may be attributable to limited access to healthcare or insurance coverage, low socioeconomic status of African-American patients and a dearth of culturally-competent mental healthcare providers. Bussing et al. (2003) found that African American children were less than half as likely to be assessed, diagnosed, and treated for ADHD as Caucasians. Their research survey among African American parents to determine common barriers to help seeking for their children with symptoms of ADHD found that across race, the most commonly cited barriers are system barriers, no perceived need and negative expectations of treatment outcomes.
It has been reported that during clinician-patient encounter, negative social stereotypes are known to shape behaviors and influence decisions made by healthcare providers. Race and ethnicity is known to adversely influence the medical care provided for other medical conditions. Minority patients with ADHD are likely to be affected by this practice as well. Historically, there has been a disproportionate pattern of diagnosis among minority populations in the category of disability. While some of this pattern of diagnosis may be related to minorities being disproportionately exposed to risk factors and psychosocial stressors and are more likely to be economically disadvantaged, the commonly used instruments of assessment which could provide misleading or invalid results when used alone to assess patients from various cultural backgrounds may explain the this phenomenon. Frequently, the quality of healthcare delivered is compromised when healthcare providers are culturally insensitive to patients. There are important cultural differences among individuals of diverse ethnic backgrounds pertaining to their attitudes and beliefs of illness, choice of care, access to care, and degree of trust toward authority figures or institutions and tolerances for certain behaviors. Investigators may have to use culturally sensitive diagnostic tools to assist them in uncovering important aspects about ADHD that may be unique to the African-American population.
Humans have the inclination to perceive or label other people or things based on their initial impressions or due to harboring elements of discrimination and stigma. Healthcare workers and physicians who care for mental health patients are not exonerated from this attribute. Eack and colleagues (2008) reported that African-Americans were three times more likely as whites to receive a diagnosis of schizophrenia based on the physician perception of the truthfulness, suspicion of symptom denial, poor insight or “uncooperativeness” of their African-American patients. Without a good understanding of cultural nuances that may provide clues about other possible diagnoses and the stigma associated with a diagnosis of mental illness among the Black community, white physicians may view black patients with suspicion which may color or affect their clinical judgment. Interestingly, the same study reported that this disparity did not appear to affect other US minority groups, such as Hispanics.
Conscious (Explicit) or unconscious (Implicit) bias or prejudices held by healthcare providers and sometimes racially-motivated discrimination by mental healthcare personnel can cause the cross-cultural diagnosis of ADHD to be challenging. In addition, biases expressed by the evaluators, interviewers or the researcher may influence the outcomes of scoring the behavioral expressions of African-American children. Depending on this held biases or cultural expectations of what constitutes “normal behaviors”, non-African American evaluators may rate American-American children with higher levels of hyperactive or disruptive behaviors even when the behavior is normal within the context of cultural expectations. It is not uncommon for parents and patients of ethnic minorities to report discrimination in receiving health care. Gingerich and colleagues (1998) reviewed several comparative studies in the 1970 which used teachers’ ratings to compare the prevalence of hyperactivity, a component of ADHD among ethnic minorities and white children. They reported one large study conducted using 1700 elementary school children from rural and urban Texan locations in which African-American children were rated as more hyperactive than expected based on their representative population when compared with schools located in white, middle-class neighborhoods where they found that the frequency of hyperactivity was consistent across all ethnic groups. The biases held by health care workers or mental health service providers can result in either under or over-diagnosis of ADHD in African-American children.
This factor may prevent the optimal care of Africa-American children with ADHD. More minority clinicians are needed to alleviate the intercultural issues of trust and communications that often arise. In 1985, out of the 30,000 Psychiatrists registered to practice in American, only about 600 were Black (Bell, Fayen & Mattox, 1998). In spite of the efforts and progress made in promoting diversity of healthcare professionals among the physician workforce, the concern about a lack of diversity continues to be an impediment to access and care, especially in the minority populations. Thus, despite some initial progress, African Americans, Latinos/Hispanics, and Native Americans continue to be underrepresented in the U.S. physician workforce. The American Medical Association Council on Medical Education Report 7 (2007) put the total number of US physicians involved in patient care in 2006 as 723,118. When categorized into Race/Ethnicity, 71.4% of these physicians were white, 15.8% were Asian, 6.4% were Hispanic, and 4.5% were Black/African-Americans. The American Medical Association report in 2012 puts the total number of Black physicians in the workforce at 3.5%, indicating a decline (Table 2). Complicating access to care, most of these physicians set up their practices in urban areas to the detriment of rural communities.
African-American families are less likely than their white counterparts to have access to the healthcare system. This may partly be due to the lower socioeconomic class and higher poverty levels among African-Americans. African-Americans tend to lack insurance coverage for psychiatric or psychological evaluations, behavior modification programs, school consultations, parent management training, and other specialized program. Substantial costs barriers exist resulting in out-of-pocket costs. Pastor and Reuben reported a significantly wide and long-standing gap in the rate of the diagnosis of ADHD based on the type of health insurance coverage. They reported that those with Medicaid insurance are most likely to be diagnosed with ADHD, followed by those with private insurance coverage, while those without insurance ended at a distant third. Even when they have insurance, the capitation imposed by the State Mental Health Services further makes access to care very difficult or inadequate, especially, for African Americans and other minority populations. Low income African American caregivers are often frustrated and feel helpless while trying to navigate the maze of the care system. There is no funded special education category specifically for ADHD. This limited access to healthcare system will contribute to less diagnosis of ADHD
\n\t\t\t\tRace/Ethnicity\n\t\t\t | \n\t\t\t\n\t\t\t\tNumber\n\t\t\t | \n\t\t\t\n\t\t\t\tPercentage\n\t\t\t | \n\t\t
White | \n\t\t\t519,840 | \n\t\t\t54.5 | \n\t\t
Black | \n\t\t\t33,781 | \n\t\t\t3.5 | \n\t\t
Hispanic | \n\t\t\t46,507 | \n\t\t\t4.9 | \n\t\t
Asian | \n\t\t\t116,412 | \n\t\t\t12.2 | \n\t\t
American Native/Alaska Native | \n\t\t\t1,594 | \n\t\t\t.16 | \n\t\t
Other | \n\t\t\t13,019 | \n\t\t\t1.3 | \n\t\t
Unknown | \n\t\t\t223,071 | \n\t\t\t23.4 | \n\t\t
Source: Physician Characteristics and Distribution in the US, 2010 Edition. American Medical Association.
Total physicians by race/ethnicity – 2008
(Total physicians = 954,224)
Comorbidities associated with ADHD include Conduct Disorders, Opposition Defiant Disorders (ODD), Depressive Disorders, Anxiety disorders, Learning disabilities and Alcohol and Drug addiction. Samuel and colleagues (1999) stated that African-American children with ADHD have higher levels of comorbid psychopathology (Opposition Defiant Disorder, Severe Major Depression, Bipolar Depression, and Separation Anxiety) than in African-American controls. They also reported that when compared to their Caucasian counterparts, African-American youths have a tendency to be more resistant or unable to seek treatment, only doing so when their symptoms are more severe. This may be responsible for a broader spectrum of the severity of ADHD symptoms in African-American youths. Epstein (2005) attributed the exhibition of more ADHD symptoms in African-American youths to fact that they are exposed to more ADHD-related risk factors. This concept was supported by Stein and colleagues (2002) who reported that African-American youth may be exposed to these risk factors at higher rates other than other youth, which may account for the higher prevalence of ADHD in African-Americans. In the general population, some of the risk factors associated with the development of ADHD and related pathology include low socioeconomic status (SES), juvenile detainee status, prenatal marijuana exposure and exposure to environmental toxins. Lead, one of the most thoroughly studied environmental toxins, is linked to impaired attention, hyperactivity, and aggression even at low levels of exposure. Bazargan and colleagues (2005) found that African-Americans living in Public Housing reportedly have higher incidence of ADHD than in the general population as a whole (19%) as compared to the pooled rate of 5%. The increased exposure resulted from paints used in housing before 1950s which contained a high percentage of lead. Other risk factors attributable to higher incidence of ADHD in African-Americans include low socioeconomic status, lack of access to healthcare (Kendall & Hatton, 2002) and high incidence of low birth weight (Breslau & Chilcoat, 2000). The higher incidence and symptomatology of ADHD in African-Americans has its consequences some of which will be further elucidated.
There appears to be an epidemic of incarceration, especially of African-American males in the United States of America. Compared to the rest of the industrialized world, America has the highest rate of incarceration, currently at about 738 per 100,000. The Justice Department reports that there are about 2.3 million inmates incarcerated in America. In 2010, Dick and Sharon Kyle, a pair of citizen journalists and information activists reported (www.LAProgressive.com) in an article titled “More Black Men in Prison than Were Enslaved II” that by race, Black males continued to be incarcerated at an extraordinary rate. They pointed out that Black males make up 35.4 percent of the jail and prison population, even though they make up less than 10 percent of the overall U.S population. They also observed that four percent of U.S. black males were in jail or prison in 2009, compared to 1.7 percent of Hispanic males and 0.7 percent of white males. This translated to black males being locked up at almost six times the rate of their white counterparts.
Black and colleagues (2010) reported that although Attention Deficit/Hyperactivity Disorder (ADHD) is associated with comorbid psychiatric diagnoses and antisocial behavior that contribute to criminality, yet studies of ADHD in offenders are few. Out of the 319 offenders they evaluated using the Mini International Neuropsychiatric Interview and Medical Outcome Health Survey; ADHD was present in 68 (21.3%) subjects. Offenders with ADHD were more likely to report problems with emotional and social functioning and to have a higher suicide risk scores. Other psychopathologies identified in offenders with ADHD include higher rates of mood, anxiety, psychotic and somatoform disorders. They are also more likely to have antisocial and borderline personality disorders. To reduce the impact of ADHD on the rate of incarceration of African-American youth, they recommended that Prison Administrators be trained to recognize the symptoms of ADHD and recommend offenders for further intensive screening rather than commitment to prisons first.
Source: www.prisonerhealth.org
Source: Justice Policy Institute Report: The Punishing Decade, & U.S. bureau of Justice Statistics Bulletin. NCJ219416. Prisoners in 2006.
Records show that many American youth are caught up in our juvenile justice system. Significant proportions of the arrests are due to either possession of or use of substances, particularly marijuana and crack cocaine. The United States Department of Justice puts the estimate of yearly arrest of juveniles at 2.5 million with approximately over a 100,000 youth under the age of 18 years incarcerated daily. Minority youth in the African-America and Hispanic population are overrepresented, accounting for more than 60% of juvenile offenders in the juvenile justice system. Interestingly, many of these detained youth have psychiatric disorders and are housed in detention facilities that lack mental health services, thereby compounding the problem.
Individuals with substance abuse disorders exhibit hyperactivity, inattention and impulsivity which are core symptoms of ADHD. These symptoms may promote antisocial behaviors which may contribute or exacerbate substance use or abuse. Conversely, substance use could worsen the symptoms of ADHD.
Studies of substance abusers and delinquents revealed a higher prevalence of ADHD comorbidity. ADHD is associated with an earlier onset of psychoactive substance use disorders, independent of psychiatric comorbidities. Retz et al. (2007) stated that children with ADHD show higher levels of substance use disorder comorbidity, particularly when it is associated with social maladaptation and antisocial behavior. Addicted delinquents with ADHD showed worse social environment and a higher degree of psychopathology, including internalizing and externalizing behaviors, when compared to addicted delinquents without ADHD. Retz and coworkers (2007) systematically examined 129 young male prison inmates for ADHD and substance use disorder. They found that 64.3% showed harmful alcohol consumption and 67.4% fulfilled DSM-IV criteria for any drug abuse or dependence. Further analysis showed that 28.8% of the participants had a diagnosis of ADHD combined type and 52.1% showed ADHD residual type. The outcome of these results should suggest adequate therapeutic interventions for addicted young prison inmates, considering the ADHD comorbidity, which is associated with additional psychopathology and social problems.
The core symptoms of ADHD, hyperactivity, inattention and impulsivity, are associated with poor developments in several areas of normal functioning. This may be reflected in African-American children with ADHD as poor academic achievements and comportment at school. Biederman and other investigators found that while hyperactivity declines over the course of the disorder, inattention symptoms persist into adulthood. Currie and Stabile, (2006) stated that this persistence of the inattention component of ADHD may be associated with numerous functional deficits, including educational failure. ADHD symptoms affect social functioning, interactions with teachers, peers, siblings and overall quality of life. Non-African-American teachers are more likely to rate African-American children as more hyperactive and disruptive in class than children from other ethnic backgrounds. The Office of Special Education Report (2005) revealed that although African-American children represent only 15% of the US population in 2001, they were overrepresented in specific learning disabilities (18%), mental retardation (34%) and are more likely to be emotionally disturbed (28%). The National Center for Education Statistics (2001) documented that African-American males make up the majority of students described as “emotionally disturbed” and are more likely to be suspended, expelled from school or subjected to corporal punishment than their white or female peers. In addition to living in extreme poverty and other social dysfunctions, it has been suggested that ADHD may be contributory to the high rates of school drop-out among African-American youth
There is evidence that ADHD places a substantial economic burden on patients, their families and third-party payers. Pelham and his colleagues (2007) projected that the economic impact of education and medical services for children diagnosed with ADHD as at 2005 was conservatively estimated at $36-$52 billion per year, which makes ADHD an important economic and social issue. It is also true that most African-American families live in poverty and are less likely to be insured or have access to mental health services. ADHD leads to increased costs in healthcare and other domains, which is likely to have economic implications for African-American families, their children with ADHD diagnosis and the society in general. Das and colleagues documented a correlation between ADHD, employment status and financial stress in middle-age individuals with ADHD. They also reported significant impairment in health, personal and social domains in their study group.
The economic implications of ADHD on African-America families may include the costs related to common psychiatric and medical comorbidities of ADHD, the indirect costs associated with work loss among adults with ADHD, the costs of managing accidents among individuals with ADHD and the costs associated with the legal issues engendered by the criminality and deviant behaviors among individuals with ADHD. Chow and colleagues (2003) reported that the economic difficulties imposed on African-Americans due to poverty and lack of health insurance makes it more likely that African-Americans resort to the use of emergency services when they receive mental health care.
A comparative study on self-reported risky sexual behaviors was conducted by Flory and colleagues (2006) in young adults (ages 18 to 26) with and without childhood attention deficit/hyperactivity disorder diagnosis. Among the participants were 175 males with a Pittsburg Longitudinal Study (PALS) diagnosis of childhood ADHD. The controls were 111 demographically similar males without childhood ADHD diagnosis. The conclusion drawn from this study is that childhood ADHD predicted earlier initiation of sexual activity and intercourse, more sexual partners, more casual sex, and more partner pregnancies. Although they pointed out that childhood conduct problems did contribute significantly to risky sexual behaviors among participants with ADHD, they also observed an independent contribution of ADHD, which suggested that the characteristic deficits of the disorder or other associated features may be useful childhood markers of later vulnerability. White and colleagues (2012) reported that ADHD symptoms were associated with greater sexual victimization during adolescence and engagement in risky sexual behaviors. The same study also found a strong association between ADHD symptoms, sexual victimization as well as risky sexual behaviors which is stronger for black women than their white counterparts. Risky sexual behaviors result in increased incidence of Sexually Transmitted Diseases (STDs), HIV/AIDS and unplanned teen pregnancies among African-American youth. Currently, The Center for Disease Control and Prevention (CDC) ranks African-American males as leading other races and gender groups in incarceration rates, new HIV infections, homicide deaths, poverty rates, and diagnosed learning disorders. In addition, the 2011 CDC Report on “African Americans and sexually Transmitted Diseases” showed that STDs take an especially heavy toll on African Americans, particularly young African American women and men. Although African Americans represent just 14 percent of the U.S. population, yet they account for approximately half of all reported chlamydia and syphilis cases and almost three-quarters of all reported gonorrhea cases.
Das and colleagues reported that inattention symptoms associated with ADHD significantly affects multiple life domains in mid-life. Marriages, spousal relationships, social interactions and health-related quality of life are all negatively impacted by ADHD symptoms. The families of children with ADHD have to contend with a greater number of behavioral, developmental and educational disturbances which often requires that more time, commitment, logistics and energy be spent. ADHD can put a strain on family relationships, especially for partners that have different views on discipline and parenting styles. The stress may be elevated if either parent feels they are bearing the burden of dealing with the child with ADHD, like taking time off to deal with behavioral problems, school attendance, medical consultations or meeting as part of ADHD management. Parents can feel overwhelmed or find it challenging to cope with their child’s disruptive behaviors. Parents may feel socially isolated if they start avoiding social events or family gatherings in hope of avoiding behavioral problems associated with their child’s diagnosis. The child with ADHD may unintentionally hurt other kids or their siblings during plays or damage property, thereby causing strained relationships. Spousal relationships may be strained. There is the danger of both or either parents spending so much time on the child with ADHD that they do not spend enough time cementing their relationship as couples. This may lead to domestic conflicts, violence and sometimes divorce. The level of attention paid by parents to the child with ADHD may engender sibling jealousy and rival with the family
Strategies and interventions
A number of strategies and interventions have been suggested to improve outcomes and reduce the impact of ADHD in African-Americans. These should be targeted at early diagnosis and treatment of ADHD, increasing awareness about ADHD, removing the stigma of mental illness, elimination of healthcare disparities, enabling access to healthcare and teaching the benefits of ADHD treatment. The importance of early diagnosis and prompt treatment cannot be overemphasized. Instead of using one-size-fits-all or the traditional diagnostic parameters, clinicians should incorporate ethnically-sensitive structured parent questionnaires or rating scales to aid in the diagnosis of ADHD in African American children. It is also suggested that care be tailored to suit the needs of African-American children with ADHD and their care-givers. This may engender more corporation and acceptance of a diagnosis of ADHD in their children and compliance with treatment programs. It is important to have an integrated health care system where patients and their families can have greater access to culturally sensitive materials or programs that will educate them about the symptoms of ADHD and the benefits of proper treatment that will improve behaviors. Parents, caregivers and mental health counselors should be involved in all the stages of diagnosis and treatment planning of African-American children with ADHD. This strategy will enable them to become partners in their own care and secure their cooperation as much as possible. This will also decrease the rate of discontinuity of care since management of ADHD of ADHD requires adherence to treatment regimens and medical appointments.
Odom and colleagues evaluated and demonstrated the usefulness of increasing awareness of ADHD through educational intervention in mothers, predominantly African Americans and reported increase in parental confidence and satisfaction among those who were taught about ADHD; since these qualities are needed in coping with this chronic illness. Same education and training should be provided to teachers who serve the African American populations.
As earlier stated, clinicians may consider using ethnically sensitive, structured questionnaires or rating scales to aid in the diagnosis of ADHD in African Americans. Obtaining a thorough medical history, conducting a thorough physical examination and utilization of guidelines on the diagnosis and evaluation of ADHD is imperative rather than relying too heavily on questionnaires for the diagnosis of ADHD.
Substantial strides at improving outcomes can be made by clinicians and healthcare providers by initiating pilot programs that will track the efficacy of a longitudinal care model whereby primary care physicians will collaborate with mental healthcare professionals. Furthermore, schools, primary care providers and service agents should be incorporated into this collaborative effort to monitor symptoms of ADHD and the response to treatment since a successful management of ADHD is contingent on cooperation and open communication among these caretakers. It is very important that adequate numbers of minority healthcare providers be accessible in schools, clinics and hospitals to address the potential issues of cross-cultural bias and mistrust. Thus, healthcare organizations must recruit and retain a diverse staff whose demographic characteristics are representative of the service area
Healthcare institutions must consider ways of offering improved access to medical services and raising the level of awareness in the community. For example, community events, churches and day care centers could be used to disseminate information and teach about ADHD in order to raise awareness regarding the importance of treatment and to lessen fears of stigmatization in the community.
It is important that care be tailored to suit the needs of various ethnic groups, such the African American community. Culturally competent medical care ensures that all patients will receive care that is compatible with their cultural beliefs and practices. The need to increase cultural competence in healthcare is described in detail in “Healthy People 2010”, which is a statement of national health objectives that are designed to identify the most significant preventable threats to health and to establish national goals to reduce these threats. The criminal code of sentencing and guidelines for African-Americans with a diagnosis of ADHD needs to be reviewed with a view to the elimination of the zero tolerance policy. Instead of confining African American youths to the prison In conclusion, healthcare providers must be diligent in their commitment to reduce or remove barriers to the proper diagnosis and treatment of ADHD in African Americans. There is the need to increase awareness in the African American community regarding the symptoms of ADHD and its treatment, and to improve cultural awareness and sensitivity towards African-American patients among clinicians to reduce the challenges involved in the cross-cultural diagnosis.
Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of fertile age. Pregnancy causes concern for the majority of patients with SLE. The risk of the disease flare during pregnancy, the possibility of fetal loss, and the safety of drugs during pregnancy are of concern. A better understanding of the pathogenesis of SLE and good use of immunosuppressive drugs allows us to better control the disease, and we should not deprive patients with SLE of the opportunity to have children. Prepregnancy information and collaboration between specialists, such as obstetricians and perinatologists, are essential to optimize maternal and fetal outcomes in SLE pregnancies. In this chapter, important issues related to fertility, optimal time of conception, risk of disease flare during pregnancy, course of pregnancy, fetal outcome, safety of various medications used to control SLE during pregnancy and lactation, and a contraceptive education are discussed [1].
\nFertility in patients with SLE is not greatly affected by the diagnosis of the disease. The decrease in fertility in SLE can be a consequence of the drugs used in the treatment of these patients, the flare of the disease, the organic damage caused by the disease, or advanced age. The use of cyclophosphamide (CYC) induces the majority of nonage-related infertility in patients with SLE, although the increasing use of mycophenolate mofetil (MMF) for the treatment of renal and extrarenal manifestations reduces the incidence due to its null ovarian toxicity. The risk of infertility due to CYC is associated with both the cumulative dose and an older age (>37 years old) of the woman at the time of treatment. The probability of maintaining fertility after treatment is greater for patients under 30 years of age, six or less monthly intravenous pulses, a cumulative dose of less than 7 g, and lack of amenorrhea before or during drug administration. It is less likely that other treatments in SLE have a significant impact on fertility, although nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested as possible contributors to infertility and it is suggested that high doses of corticosteroids have some effect on the cycle menstrual through its effect on the hypothalamic pituitary axis (HPA).
\nPatients with SLE may have menstrual disturbances or even amenorrhea secondary to very active disease. In addition, serum levels of anti-mulleriana hormone (AMH) are lower in patients with SLE not treated with CYC than in controls matched by age. It is important to emphasize that renal failure induced by lupus glomerulonephritis can cause hypofertility or infertility due to an alteration of the HPA, which can be reversed with kidney transplantation.
\nThe profile of autoantibodies does not seem to affect fertility in women with SLE. However, the study of aPL in women with lupus is essential for predicting gestational risk, although recent controlled studies do not support an association between aPL and infertility or in vitro deficient fertilization (IVF). Evaluation or treatment of aPL in infertile women is not recommended.
\nOlder age is an important factor of infertility in SLE, as it is in the general population. Female fertility decreases with age due to the progressive loss of the ovarian reserve; many patients with SLE are older when they try to conceive and may encounter difficulties related to age. The onset of SLE is more frequent in the first years of reproduction, and it is advised to avoid pregnancy when the disease is active. Premature ovarian failure (persistent amenorrhea with elevated levels of follicle-stimulating hormone before age 40) may be of autoimmune etiology in the general population but is rarely associated with systemic autoimmune diseases such as SLE [1, 2]. The study of anti-ovarian antibodies has contributed little to this pathology. However, treatment with corticosteroids and/or immunosuppressants has reversed the process in some cases.
\nPreserving fertility in women with SLE involves limiting cytotoxic drugs when possible and protecting the ovaries during treatment; however, prompt and effective therapy for a severe disease often takes precedence. The cryopreservation of oocytes or embryos is an effective option but requires ovarian stimulation, which may be impractical given the usual need to institute therapy quickly to avoid damage, as well as the risk of hyperstimulation in a patient with active SLE. The age of the patient to whom CYC is administered is not modifiable, but an effort must be made to minimize the total dose of CYC. The use of MMF may be the best option. Treatment with agonists of the gonadotrophic hormone receptor (GnRH) during CYC therapy to minimize ovarian toxicity has become a common practice. Ovarian toxicity amenorrhea due to CYC has been the classic clinical sign. Now, the measurement of the AMH provides us with a better evaluation of the ovarian reserve. In a study of patients with SLE who received leuprolide with a GnRH agonist between 10 and 14 days before the CYC pulse therapy, a 68% increase in the ovarian reserve was estimated compared to patients with SLE who had not received this treatment. The GnRH agonist should not be administered immediately before the CYC. When administered during the follicular phase of the cycle, it can stimulate the ovaries and worsen ovarian damage. Patients without therapy with GnRH agonists before their first infusion can start treatment after the first cycle and receive treatment at monthly intervals thereafter [2].
\nSLE patients may be strongly advised to avoid pregnancy, particularly when they have severe disease-related damage or active disease or are taking teratogenic medications. Consequently, contraceptive options should be discussed with all female patients of reproductive age. Counseling patients to defer pregnancy relies on the assumption that they will utilize safe and effective contraception. In practice, SLE patients currently underutilize effective contraception, even those taking teratogenic medications [2]. Contraceptives vary in safety and efficacy. Long-acting reversible contraceptives such as intrauterine devices (IUDs) or subdermal implants have the greatest efficacy. IUDs generally contain either progesterone (levonorgesterol) or copper. Although IUDs have a low risk of infection, patients treated with immunosuppressive medications have not been specifically studied. However, HIV-infected women who have been studied do not have a greater risk of infection. Combined hormonal contraceptives include the pill, transdermal patch, and vaginal ring. Serious side effects include a three- to fivefold increased risk of venous thromboembolism and a twofold increased stroke risk. Medications commonly used for patients with SLE, such as warfarin and MMF, may interact with these agents and alter their efficacy. Concern regarding estrogen-induced flare previously has limited the use of oral contraceptives in patients with SLE. Two recent prospective studies in women with stable SLE showed no increased risk of flare with combined oral contraceptives. But oral contraceptives containing the progestin drospirenone can increase serum potassium and be dangerous in patients with nephritis or who also take angiotensin-converting enzyme (ACE) inhibitors. The vaginal ring and the patch may further increase thrombosis risk compared to oral combined contraceptives, and their safety in SLE has not been studied. No forms of estrogen-containing contraceptives are advised for use in aPL-positive patients due to the increased risk for thrombosis [3]. Progesterone-only contraceptives include oral and intramuscular forms, IUDs, and a subdermal etonogestrel implant. Depot medroxyprogesterone acetate (DMPA) injections may decrease bone density when used chronically, a concern in corticosteroid-treated patients. Progesterone-only contraceptives represent a safe and effective option for aPL-positive patients; with the possible exception of DMPA, the risk for thromboembolism is very low, and they may decrease menstrual blood loss. Emergency contraception can be considered for all SLE patients, including aPL-positive patients. Long-acting reversible contraceptives are preferable for most SLE patients, but every decision regarding contraception must balance the risk and efficacy of the method with the risk of unplanned pregnancy.
\nFertility is generally unimpaired in patients with systemic lupus erythematosus (SLE), unless they have been treated with cyclophosphamide (CYC). Although CYC is less commonly used for nephritis than in the past because of the availability of MMF, prevention of CYC-induced infertility remains an important concern. Concurrent gonadotropin-releasing hormone (GnRH) analogue therapy, usually leuprolide, appears to decrease risk of premature ovarian failure by CYC. Embryo and oocyte cryopreservation is options to preserve fertility in patients who are stable enough to safely undergo ovarian hyperstimulation. Patients with lupus may undergo assisted reproduction techniques, including in vitro fertilization (IVF). Ovarian hyperstimulation syndrome (OHSS) is a rare complication of IVF resulting in a capillary leak syndrome; severe OHSS increases risk for thrombosis and renal compromise. Even in a well-controlled cycle, elevated estrogen levels may increase risk of flare and thrombosis in SLE patients. However, thrombosis in aPL-positive patients undergoing IVF is rare, but most reported patients have been treated prophylactically with anticoagulants. Prophylactic anticoagulation may be considered in patients with high-risk aPL profiles and is mandatory for those with confirmed APS. However, aPL antibodies as a cause of failed IVF or infertility is not accepted, and anticoagulation is not indicated to improve IVF cycle outcome [2, 3].
\nGood information to the patients and pregnancy planning is essential for a woman with SLE who wants a child. Pregnancy planning is a key point for women with SLE. Postponing conception until the disease is inactive for at least the previous 6 months significantly improves the results. Women with irreversible lesions in vital organs are more likely to suffer maternal-fetal morbidity and mortality during and after pregnancy. The pregnancy should be delayed, such as a severe disease flare in the previous 6 months, a recent stroke, and active lupus nephritis. In some situations, pregnancy may be contraindicated (\nTable 1\n). A profile of autoantibodies, such as aPL (anticardiolipin, anti-β2 glycoprotein I, and lupus anticoagulant), serum levels of complement, anti-SSA, and anti-SSB antibodies [4], is essential as risk factors for complications during pregnancy. Keeping the SLE inactive and the function of organs with safe medications during pregnancy should be a goal. There is an increased risk of complications among women with severe impairment of organ function, with or without serious pre-existing damage. The care of pregnant women with SLE must focus on three mainstays: a coordinated medical-obstetrical care, a well-defined management protocol, and a well-structured prenatal follow-up.
\nPreconception visit checklist | \nContraindications to pregnancy | \n
---|---|
Age | \nSevere lupus flares within the previous 6 months | \n
Any previous pregnancy? | \nSevere restrictive lung disease (FVC < 1 L) | \n
Previous pregnancy complications? | \nHeart failure | \n
Presence of severe irreversible damage? | \nChronic renal failure (Cr < 30 mg/dL) | \n
Recent or current lupus activity? | \nStroke within the previous 6 months | \n
Presence of antiphospholipid antibodies/syndrome? | \nPrevious severe preeclampsia of HELLP syndrome despite therapy with aspirin and heparin | \n
Other chronic medical conditions? | \nSevere lung hypertension | \n
(Hypertension, diabetes, etc.) | \n(Estimated systolic PAP > 50 mm Hg or symptomatic) | \n
Previous nephritis or active nephritis | \n\n |
Current treatment: any forbidden drugs (including cyclophosphamide, methotrexate, mycophenolate, thalidomide, or thalidomide lyks, angiotensin-converting, enzyme inhibitors, angiotensin II receptor blockers, diuretics, and statins) | \n\n |
Positive anti-Ro and anti-La | \n\n |
Anti-DNA, complement levels C3 and C4 | \n\n |
Preconception visit checklist and contraindications to pregnancy in women with SLE.
Abbreviations: PAP, pulmonary arterial pressure; FVC, forced vital capacity.
In pregnancy, it is necessary to perform routine pregnancy testing plus other tests that include a complete blood count, kidney and liver function, and proteins in a 24-hour urine collection (\nTable 2\n). Complementary studies should include additional tests such as complement study (C3 and C4), aCL, LA, aβ2GPI, anti-DNA, anti-SSA, and anti-SSB antibodies [4]. Evaluate the activity of the disease during the prenatal phase. The hormonal changes during pregnancy cause an alteration of the domain of Th1 to Th2 lymphocytes, and, consequently, it is expected that autoimmune disorders involving the Th2 response, such as SLE, are activated. In general, it is accepted that pregnancy can lead to higher rates of outbreaks of the disease, ranging from 25 to 65%. Skin rashes and musculoskeletal symptoms are less common, while renal and hematological flares are more frequent. The risk of flare seems to be related to the onset of disease activity 6–12 months before conception. There is an increased risk of flares during pregnancy when there is lupus nephritis at conception and even in women with pre-existing nephritis in remission. One study showed an exacerbation rate of 30% of SLE activity during pregnancy or postpartum in women with pre-existing lupus nephritis. It is sometimes difficult to distinguish signs and symptoms related to pregnancy from those due to SLE. Some ambiguous manifestations such as fatigue, headaches, arthralgias, edema, hair loss, palmar and malar erythema, anemia, and thrombocytopenia can be confused with clinical manifestations of SLE. An evaluation by physicians experienced in pregnant women with SLE is important. Blood tests with basal blood counts and urinalysis with measurement of proteinuria are useful to control the state of the disease and identify the flare. The production of C3 and C4 increases in the liver during pregnancy, and, therefore, their levels may be within the range of normality in cases of active SLE. Relative variations of complement are more important than absolute levels, and a 25% drop in serum complement levels may suggest a flare of lupus. The determination of the products of complement degradation would be the best way to identify a greater activation. Currently, we have indices to measure the activity of SLE during pregnancy, such as the pregnancy activity index of systemic lupus erythematosus (SLEPDAI) and the index of lupus activity in pregnancy (LAI-P). In practice, the clinical judgment of an experienced clinician is still considered the gold standard, and these indices are essential for publications on SLE and pregnancy. The SLEPDAI scale is an instrument similar to the SLE disease activity index (SLEDAI) to evaluate the activity of lupus, assigning different scores for the various clinical and laboratory manifestations of lupus activity, however, taking into account the changes, physiological factors of pregnancy, and main pathologies of the pregnancy-puerperal cycle that can simulate an active SLE. The risk of hypertensive disorders during pregnancy increases in the context of active lupus nephritis. The frequency of preeclampsia varies from 7.5 to 22.5% for all women with SLE. Renal involvement of lupus is often associated with hypertension, and the diagnosis of preeclampsia is difficult because it may coincide with chronic hypertension exacerbated during pregnancy. Likewise, in the case of women with SLE with residual glomerular lesions, an increase in proteinuria can be observed, due to the increase in the glomerular filtration rate during pregnancy, and this fact is not related to preeclampsia. The diagnosis of preeclampsia may be more difficult due to the increase in blood pressure and previous proteinuria. The differential diagnosis of preeclampsia in patients with lupus may be facilitated by changes in the C3, C4, and CH50 measurements, since a reduction in these levels is expected during lupus activity. Other laboratory tests are useful to perform a differential diagnosis, such as an abnormal urinary sediment, erythrocytic dysmorphia or cell casts, and increased titers of anti-DNA antibodies (common in lupus nephritis). SLE of onset during pregnancy should be considered as an active lupus and may be associated with a worse outcome of pregnancy. Differentiating preeclampsia into an early SLE during pregnancy is a challenge and often delays the diagnosis of SLE. Among patients with stable SLE at the time of conception, it is expected that the activity of the disease does not worsen, and even if so, the flare is usually mild and involves some type of treatment modification.
\nPrepregnancy | \nEvery 6–8 weeks\n1\n\n | \n
---|---|
Complete blood count with platelets | \nComplete blood count with platelets | \n
Comprehensive metabolic panel | \nComprehensive metabolic panel | \n
Prothrombin time/partial thromboplastin tine | \nUrinalysis with microscopy | \n
Urinalysis with microscopy | \nSpot protein/creatinine ratio | \n
24-hour urine protein and creatinine clearance\n2\n\n | \nAnti-dsDNA | \n
Spot protein/creatinine ratio | \nComplement levels (C3, C4) | \n
Anti-dsDNA | \nUric acid | \n
Anti-Ro/SSA and anti-La/SSB antibodies | \nsFlt-1/PlGF ratio (>20 weeks) | \n
Lupus anticoagulant\n3\n\n | \n\n |
Anticardiolipin IgG, IgM\n3\n\n | \n\n |
Anti-β2 glycoprotein I IgG, IgM\n3\n\n | \n\n |
Complement levels (C3, C4) | \n\n |
Uric acid | \n\n |
Systemic lupus erythematosus pregnancy evaluation and monitoring.
Adjust interval of monitoring based on clinical situation.
In patients with proteinuria, consider repeating 24-hour urine test each trimester.
If positive for first time, repeat in 12 weeks.
Fetal complications are frequent in patients with SLE. Miscarriages and intrauterine fetal death can occur in 20% of pregnancies in patients with SLE. Patients with a history of nephritis have a higher risk of such adverse outcomes. The rate of restriction of fetal growth (FGR) is close to 30%, even in mild disease, with an increased risk if there is renal involvement. Several studies concluded that the result of the mortality rate for women with SLE tends to be higher, a condition strongly associated with the presence of flares of the disease during pregnancy. Serial obstetric ultrasound is the most important method to guide the monitoring of fetal growth. The measurement of the length of the cranial crown in the first trimester is presented as the most accurate measurement. At 16–22 weeks of gestation, an anatomical survey should be followed that considers the diagnosis of fetal anomalies, which also allows the first growth monitoring. In each 4-week period, new scans must be performed, measuring the volume of amniotic fluid. If preeclampsia is diagnosed, the interval should be reduced. The monitoring of fetal vitality is an important part of the prenatal care of patients with SLE. This should include the nonstress test (NST), the biophysical profile (BPP), and the Doppler velocimetry of the fetal umbilical artery, beginning at 26–28 weeks and continuing weekly until birth. In patients with SLE, alterations of the umbilical artery Doppler velocimetry should be handled in a similar way to those without the condition. The normal evaluation of these tests has a high negative predictive value for fetal death. A relationship exists between abnormal uterine artery Doppler and posterior fetal loss, preeclampsia, FGR, and preterm birth. For women with anti-SSA/anti-SSB antibodies, fetal echocardiography should be performed between 18 and 26 weeks to exclude congenital heart blockage of the fetus. An urgent referral to a tertiary care center should be requested in case of abnormal fetal heart rate, mainly a low heart rate.
\nAn active SLE is harmful to the mother and the fetus, and an appropriate reflection is necessary between the risks and benefits of the indicated treatment. In practice, it is common for women with SLE to interrupt their medication before conception, for fear of fetotoxicity, which happens through medical advice and proper planning [5]. Stopping the medication can lead to an active SLE and unfavorable pregnancy outcomes. Immunosuppressive treatment in pregnant women with quiescent lupus should not be changed unless it induces fetal malformations. The glucocorticoids and antimalarials are the drugs most used in the treatment of lupus and should be maintained at the same doses during pregnancy. Prednisone at a dose of 5–10 mg/day is considered safe and sustainable during pregnancy. The mild flare of the disease can be treated with low doses of prednisone (less than 20 mg/day), and higher doses of corticosteroids, such as intravenous pulses, will be indicated to treat moderate to severe lupus activity. The antimalarial is not teratogenic and is recommended to prevent the activity of the disease and reduce the risk of cardiac neonatal lupus in patients with anti-Ro antibodies. The use of immunosuppressants is possible during pregnancy, and azathioprine is the safest. Changing other immunosuppressants to azathioprine in a patient with SLE who wants pregnancy is recommended. Some recent report describes leukopenia, thrombocytopenia, and slow development of children exposed to azathioprine during pregnancy. Cyclosporine and tacrolimus, classified as category C by the Federal Drug Association (FDA), are safe during pregnancy initially demonstrated in pregnant women with kidney transplantation. CYC should not be prescribed during the first trimester for causing fetal chromosome, if it can be used during the second or third trimester for severe flares not controlled with pulses of methylprednisolone or other immunosuppressants. The use of CYC during the second and third trimesters does not seem to increase the risk of congenital anomalies, although spontaneous abortions and premature labor may be more frequent. Treatment with mycophenolate mofetil may be another option during the second and third trimesters, although more experience is lacking. Leflunomide is associated with teratogenic and fetotoxic effects in animals, and its metabolite is detectable in plasma up to 2 years after the interruption. In pregnant women, it is formally contraindicated, and pregnancy should be excluded before starting a treatment with leflunomide. Methotrexate, classified as drug X by the FDA, is teratogenic and produces abortion at high doses; therefore, it is contraindicated in pregnancy. If used in the first trimester, it is associated with FGR and some important malformations, such as absence or hypoplasia of the frontal bones, craniosynostosis, large fontanelle, and ocular hypertelorism. Thalidomide or thalidomide-like is used for the treatment of cutaneous lupus, producing malformations in the fetus, such as phocomelia by thalidomide. Rituximab has a very low transplacental transfer during the first trimester of pregnancy, and some studies of safe pregnancies and deliveries have already been reported in cases of exposure; in the second or third trimester, it can cross the placenta and induce severe neonatal lymphopenia. Therefore, in these cases, live vaccines should be avoided in these children during the first 6 months of life. High blood pressure is a common condition among patients with lupus nephritis; an adequate treatment of blood pressure during pregnancy can reduce the progression of the disease and avoid several adverse pregnancy outcomes. The labetalol, nifedipine, hydralazine, and methyldopa are safe medications to treat hypertension in pregnant women. Angiotensin-converting enzyme (ACE) inhibitors should be avoided due to their association with multiple congenital anomalies. A low dose of aspirin is recommended, since it reduces the risk of preeclampsia and perinatal death; In addition, it is associated with an increase in birth weight in those cases with risk factors, including kidney disease. Complete anticoagulation with low molecular weight heparin (LMWH) is recommended if there has been a previous thrombotic event. Calcium supplements are required, mainly for those women who use corticosteroids and heparin. Also, vitamin D supplements can be given, but it does not reduce unfavorable obstetric risks.
\nMany physiological changes in pregnancy can overlap with the characteristics of active disease, which makes differentiation difficult (\nTable 3\n). Some common laboratory tests also become less reliable: mild anemia and thrombocytopenia are common, the erythrocyte sedimentation rate (ESR) increases, and up to 300 mg/day proteinuria can occur during normal pregnancy. Complement levels increase by 10–50% during normal pregnancy and may appear to remain in the “normal” range, despite the activity of the disease. Anti-DNA antibodies may be useful in the evaluation of disease activity. The scales of activity of the specific disease of pregnancy, the activity index of pregnancy SLE (SLEPDAI), the LAI-P, and the BILAG2004-Pregnancy index have been developed with modifications in the descriptors. A combination of laboratory parameters along with clinical judgment may be the best tool to evaluate the activity of the disease. Based on the numerous risks associated with pregnancy, it is recommended that women with SLE have a preconception assessment and multidisciplinary management with maternal-fetal drugs and rheumatology during pregnancy. Active SLE at the time of conception is a predictor of adverse outcomes. It is suggested that the disease remain inactive for 6 months before attempting pregnancy. Laboratory tests should include, at a minimum, antiphospholipid antibodies (LA, IgG and IgM aCL, IgG, and IgM anti-aβ2GPI I antibodies), anti-Ro/SSA and anti-La/SSB antibodies, and an evaluation of renal function (creatinine, protein/creatinine ratio in urine). Women who have anti-Ro/SSA and anti-La/SSB antibodies should have intensive fetal monitoring for cardiac arrest with fetal echocardiography by weekly pulsed Doppler (to measure the mechanical PR interval) beginning at 16–18 weeks and continuing up to 26–28 weeks of pregnancy. Ideally, all women with SLE should receive HCQ and low doses of aspirin during pregnancy, unless contraindicated. Women who continue HCQ during pregnancy have fewer outbreaks of disease and better outcomes as well as mothers with positive anti-Ro/SSA and anti-LA/SSB antibodies. Low-dose aspirin initiated at 12–16 weeks of gestation reduces the risk of preeclampsia and fetal growth restriction [6]. The interruption of medications used to control the activity of the disease increases the risk of flares and complications associated with pregnancy. Serial ultrasound exams should be performed to assess fetal growth and fetal monitoring before delivery should begin in the third trimester. Renal involvement is common in patients with SLE and may be suspected in the presence of proteinuria or elevated serum creatinine. Hypertension and nephrotic syndrome consist of intense proteinuria, hypoalbuminemia, and peripheral edema, and patients have characteristically low levels of complement (C3) and high levels of anti-DNA. The involvement of the renal vasculature in cases of lupus nephritis is a sign of poor prognosis. In thrombotic microangiopathy, damage to the endothelial cells of small arterioles and capillaries results in thrombosis and mortality. Neuropsychiatric symptoms observed should be considered and excluded, including electrolyte abnormalities, infection, renal failure, and the effects of drugs. In the absence of a standard gold diagnostic test, this can represent a significant clinical challenge, especially in pregnancy and the postpartum period, where specific conditions of pregnancy, such as preeclampsia and eclampsia, can produce the same symptoms. The APS is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity in the presence of persistent antiphospholipid antibodies. A small subset of patients with APS (<1%) develops multiple organ failure secondary to a disseminated thrombotic disease, a condition called catastrophic APS (CAPS) that has a mortality rate of up to 50%.
\n\n | Pregnancy changes | \nSLE activity | \n
---|---|---|
Clinical features | \nFacial flush | \nPhotosensitive rash | \n
\n | Palmar erythema | \nOral or nasal ulcers | \n
\n | Arthralgias | \nInflammatory arthritis | \n
\n | Fatigue | \nFatigue, lethargy | \n
\n | Mild edema | \nModerate to severe edema | \n
\n | Mild resting dyspnea | \nPleuritis, pericarditis | \n
Laboratory features | \nMild anemia | \nImmune hemolytic anemia | \n
\n | Mild thrombocytopenia | \nThrombocytopenia | \n
\n | \n | Leukopenia, lymphopenia | \n
\n | Mild increased ESR | \nIncreased inflammatory marker levels | \n
\n | Physiologic proteinuria | \nProteinuria > 300 mg/day | \n
\n | \n | Active urinary sediment | \n
Overlapping features of pregnancy and systemic lupus erythematosus (SLE).
Abbreviation: ESR, erythrocyte sedimentation rate.
The treatment of flares during pregnancy is guided by the severity and involvement of the organ, similar to the state of nonpregnancy. However, the choice of agents is limited to safe medications, as discussed above. The steroids should be used in the lowest possible doses, but short cycles of high doses can be used for flare control. NSAIDs can produce malformations, and in general their indication in the SLE is in disuse. The antimalarial should be continued throughout pregnancy. Azathioprine and anti-calcineurin can occur throughout pregnancy. Azathioprine is a safe immunosuppressant with much experience in pregnancy, although delays in the development of the offspring have recently been reported. IVIg and plasmapheresis are still alternative options, but the increased risk of thrombosis with IVIg and fluid overload should be considered, although it is rarely necessary if we exclude intravenous Ig treatment of severe thrombocytopenia in pregnancy. Physiological changes in pregnancy such as an increase in glomerular filtration rate and renal plasma flow can worsen pre-existing kidney disease. However, in theory, a rapid decrease in the levels of the pregnancy hormone, particularly estrogen, may be advantageous. It is known that the immunosuppressive drugs used to treat SLE, such as CYC, cross the placenta and have teratogenic effects. In addition, this particular medication has been associated with premature and irreversible ovarian failure.
\nLupus nephritis is an important risk factor for both maternal and fetal complications. A meta-analysis of 37 studies from 1980 to 2009 included 2751 pregnancies with SLE: the SLE flare rate was 25.6%, and the rates of preterm birth and IUGR were 39.4 and 12.7%, respectively. Positive associations were identified between preterm birth and active nephritis, hypertension and active nephritis, and preeclampsia and history of nephritis [7]. Up to 25% of women with SLE will develop preeclampsia compared to 5% in the general population. Doctors who treat lupus and pregnancy should ask themselves questions like does the presence of increased proteinuria and hypertension represent a flare or does the presence of increased proteinuria and hypertension represent the onset of preeclampsia? At the beginning of pregnancy, the presence of new or worsening proteinuria and hypertension will almost always represent a flare of lupus nephritis. However, beyond 20 weeks of gestation, differentiating a flare of preeclampsia poses a diagnostic as well as a therapeutic challenge (\nTable 4\n). Flare of lupus nephritis in pregnancy may be the first presentation of lupus and is relatively rare in those without previous nephritis or inactive nephritis at the beginning of pregnancy. However, if a woman has proteinuria, hypertension, renal function decreased at the beginning of pregnancy, and a history of lupus nephritis, she is likely to have a flare of lupus nephritis. The clinical history plus appropriate biochemical investigations is key to the diagnosis of clinical complications in SLE and pregnancy. The complement should be normal or high in pregnancy because it behaves as an acute phase reactant since this is pregnancy. The decrease in complement, even within the normal range, should alert us to a possible flare of SLE and more when associated with an increase in anti-dsDNA. If proteinuria is significant and unexpected, it can mean a change in immunosuppression and even renal biopsy if the woman is in the first trimester or in part during the second trimester, although it is only necessary if the clinic and laboratory are discordant. Always keep in mind if the woman is at risk of bleeding after the biopsy and for how long anticoagulation can be delayed in a pregnant woman with intense proteinuria and possibly phospholipid antibodies who, therefore, have a high risk of thrombovenous embolism, since the procoagulant factors are added, pregnancy, nephropathy, SLE activity, and/or aPL. If the risk of having thromboembolism outweighs the benefit of a firm diagnosis, a biopsy should not be done. However, if there is a biochemistry compatible with a flare of lupus, patient’s history contains nephritis flares and it is seems that it is going to be repeated; a kidney biopsy could be justified. The distinction of nephritis from lupus of pregnancy preeclampsia (from 26/40 weeks of gestation) can be difficult. In both, there will be an increase in proteinuria, hypertension, generalized symptoms, thrombocytopenia, and kidney damage. In women with isolated preeclampsia, there should be no hematuria, urinary cylinders, a decreasing complement, or increasing anti-dsDNA. However, a flare of lupus nephritis increases the risk of preeclampsia, so, again, distinguishing the two can be a challenge for the clinician. The two treatments are different; preeclampsia requires delivery sooner rather than later, and lupus nephritis requires immunosuppressive treatment. It is not yet a usual practice, but it is likely to be exceptionally useful, measuring angiogenic and antiangiogenic factors, to determine if there is preeclampsia present. Women with APS and SLE who developed preeclampsia had a median of sFlt-1 (tyrosine kinase similar to soluble fms), low placental growth levels (PIGF), and a significantly higher sFlt-1/PlGF ratio, and significantly higher PIGF levels lower compared with women with APS and SLE and without preeclampsia after 12 weeks of gestation. These differences increased with gestational age. The sFlt-1/PlGF ratio became a significant predictor of preeclampsia at 12 weeks, showing the highest levels at 20, 24, and 28 weeks of gestation [8, 9]. Later, the fall of the placental growth factor predicted the appearance of preeclampsia even in women with pre-existing chronic kidney disease. A recent publication highlights the evidence (or more commonly the lack of evidence) for the best use of antirheumatic drugs before and during pregnancy. Women who take azathioprine, hydroxychloroquine, cyclosporine, and tacrolimus can safely breastfeed their babies, so women who take these medications should not be discouraged from breastfeeding.
\nClinical measure | \nPreeclampsia | \nLupus nephritis | \n
---|---|---|
Time | \n>20 weeks | \n>20 weeks | \n
Hypertension | \nPresent | \nOften present | \n
Urine active sediment | \nRare | \nCommon | \n
Onset of proteinuria | \nAbrupt, after 20 weeks | \nAbrupt or gradual, anytime | \n
Uric acid | \n>4.9 mg/dl | \n<4.9 mg/dl | \n
C3 and C4 | \nUsually normal | \nUsually low or decreasing | \n
Complement products | \nNormal | \nUsually higher | \n
Anti-DNA | \nNegative or stable | \nPositive or increasing | \n
Lupus activity | \nNo | \nYes | \n
Urine calcium | \n<195 mg/day | \n>195 mg/day | \n
Thrombocytopenia | \nYes (HELLP) | \n20% of SLE | \n
Liver function test | \nMay be elevated (HELLP) | \nUsually normal | \n
Kidney biopsy | \nGlomeruloendotheliosis | \nSLE nephritis | \n
sFlt-1/PlGF ratio | \nHigher | \nNormal | \n
Differentiation of preeclampsia from lupus nephritis flare in pregnancy.
Abbreviations: HELLP, hemolysis, elevated liver enzymes, and low platelets; SLE, systemic lupus erythematosus; sFlt-1, soluble fms-like tyrosine kinase; PlGF, placental growth factor.
There are still no safety data on the MMF, so breastfeeding is discouraged if MMF is required. The woman with SLE and pregnancy should be treated as high-risk. At the controls ask for symptoms of the disease to detect SLE flare, and always check the blood pressure to detect preeclampsia. A blood and urine test should be done every quarter to detect biological changes in the complement and anti-DNA that suggest a flare. The fetus must be carefully monitored to detect growth and blood flow. Good multidisciplinary coordination among obstetrician, nephrologists, rheumatologists, and nursing experts is essential for better results.
\nPregnancy in women with SLE and aPL-positive courses with obstetric is 80% of cases. The current standard treatment for patients with obstetric includes LDA (75–100 mg/day) and low molecular weight heparin (subcutaneous enoxaparin, dalteparin, nadroparin, or subcutaneous tinzaparin) or unfractionated heparin. These recommendations are based on the results of randomized controlled trials comparing LDA alone or in combination with heparin with APS [7]. Kutteh et al. reported a significant improvement in the rate of live births with LDA and heparin versus LDA alone (80 versus 44%, P < 0.05). Rai et al. showed a significantly higher rate of live births with LDA and unfractionated heparin (5000 units) versus LDA alone (71 versus 42%, OR, 3.37, 95% CI, 1.40–8.10). However, no differences were found in the results with the combined treatment versus the LDA in two other randomized trials, both with LMWH, with live birth rates close to 80% in both groups. The heterogeneity in the findings seems to be attributed to the relatively poor results in women who received LDA alone in the two previous studies. In addition, data from observational studies have reported pregnancy success rates of 79–100% with LDA alone in this subgroup of women, although many of these cases had low levels of aPL antibodies. The current recommendation for the treatment of obstetric APS is to initiate LDA plus LMWH at therapeutic doses.
\nAll women should be evaluated for risk factors for venous thromboembolism and should receive postpartum thromboprophylaxis. The Royal College of Gynecology in the United Kingdom, for example, recommends, for aPL-positive women without clinical manifestations of APS, 7 days after thromboprophylaxis of labor, and for women with APS, this extends to 6 weeks. All women with APS can deliver natural light, unless there are obstetric reasons to suggest otherwise. In addition, all women should be encouraged to stop smoking and reduce/discontinue alcohol consumption in accordance with the national pregnancy guidelines. Patients with a recent thrombotic event in the last 3 months, particularly high blood pressure and/or uncontrolled, should be encouraged to postpone new pregnancies. Patients with pulmonary hypertension in general are advised not to get pregnant. Women with previous thrombosis should receive long-term anticoagulation once the risk of postpartum hemorrhage has stabilized. Both AVK (antivitamin K) and heparins are compatible with breastfeeding. With respect to fetal monitoring during pregnancy, the bilateral uterine notch between 23 and 25 weeks of gestation has been shown to be an independent risk factor for the development of early-onset preeclampsia and gestational hypertension. Therefore, the bilateral notch of the uterine artery should be considered in the risk assessment for the development of these pregnancy complications. The evaluation of thrombotic risk should also be considered in patients with a history of obstetric primary health center. Among others, Lefevre et al. demonstrated that patients with obstetric APS have a higher thrombotic risk compared to healthy women (3.3 versus 0–0.5/100 patient years), even if treated with LDA. Similarly, in a 10-year observational study of 1592 women with pure obstetric SAP and no history of thrombosis, Gris et al. demonstrated that the LA was a risk factor for superficial and superficial venous thrombosis and unprovoked distal and similar results have been demonstrated in other studies.
\nThe current treatment to prevent obstetric morbidity in primary health center (PHC) has improved the outcome of pregnancy at a rate of live births of more than 70%. Given that 30% of women continue to have complications during pregnancy, international groups are currently evaluating different options to improve pregnancy outcomes in women with APS. The additional use of low doses of steroids has been evaluated in refractory APS. It has been suggested that intravenous immunoglobulin improves pregnancy complications in obstetric PHC. Treatment with pravastatin suggests a beneficial role in those women with preeclampsia related to established aPL. In their case series, 11 patients are treated with pravastatin 20 mg/day in addition to the standard treatment, while the controls continued alone with LDA and LMWH. In all patients exposed to pravastatin, signs of preeclampsia, such as blood pressure and proteinuria, improved and signs of placental perfusion remained stable without further deterioration compared to the control group. HCQ has also been evaluated. The HCQ immunomodulator can have beneficial effects not only in the treatment of thrombotic APS but also in the prevention of pregnancy complications [10]. The European randomized controlled multicenter trial “HYPATIA” will evaluate the role of HCQ versus placebo in pregnant women with aPL and, hopefully, provide stronger evidence on the use of HCQ in this context. Complement activation, and therefore a potential role for eculizumab, has also been introduced as a potential target for therapy with APS. The participation of complement activation was investigated for the first time in murine models of pregnancy morbidities related to aPL, and increasing evidence is emerging from both in vitro and in vivo studies. The complement can be activated by binding of the C3 fragment to the Fc receptor of aPL antibodies or by the formation of autoantibodies against C1q, which are frequently detected in patients with APS. The activation of the complement pathway and, consequently, the production of inflammatory molecules such as C5a by aPL, can directly activate platelets and monocytes, inducing the coagulation cascade, which leads to the clinical manifestations of APS. Although in the current literature several case reports describe the successful use of eculizumab in severe cases of APS, such as catastrophic antiphospholipid syndrome (CAPS) and cases of APS and thrombotic microangiopathy, the potential role of eculizumab should be further investigated.
\nPregnancies in women with anti-Ro and anti-La have an increased risk of developing neonatal lupus (NLS) with or without lupus. Maternal antibodies cross the placental barrier giving a passively acquired fetal autoimmunity. Cutaneous lesions of subacute lupus and hematologic and/or hepatic alterations of the NLS tend to resolve with the elimination of maternal antibodies from 6 to 8 months of age, but the lesion of the developing fetal cardiac conduction pathway can be irreversible. Cardiac injuries include conduction defects, structural abnormalities, cardiomyopathy, and congestive heart failure, but the most serious complication is the development of irreversible complete heart block (CHB), which is associated with a high fetal mortality of 20%. NLS can affect 2% of pregnancies exposed to anti-Ro, but recurrence rates in new pregnancies are 16–20% after a first NLS event. The majority (up to 70%) of the survivors require the insertion of a permanent pacemaker and periodic changes of the same as the child will grow. The CHB may be preceded by lower degrees of driving delays, although it may be sudden onset. Most of the events occur between 18 and 24 weeks of gestation, but there are later cases, and even postpartum CHB has been described. Early detection and initiation of treatment could stop progression to CHB, but reversal of established CHB has not been reported. Multiple monitoring tools have been proposed for the early detection of cardiac conduction disorder, but fetal Doppler echocardiography remains the most widely used method. The most vulnerable period is between 18 and 24 weeks of pregnancy, so it is recommended in this period of pregnancy to monitor weekly all exposed fetuses, and then every 2 weeks. The detection of an early conduction defect with a prolonged RP interval should indicate the start of a prophylactic treatment to avoid CHB, although we do not have any effective guidelines. The maternal administration of fluorinated corticosteroids and beta-agonists has shown benefits in some specific cases. The treatment of established CHB remains an unresolved problem with minimal benefit with any available approach. The high risk of recurrence in subsequent pregnancies justifies prophylactic therapy for pregnancies at risk. The beneficial effects of IVIg were reported in open studies, but two randomized controlled trials were negative. Both trials have been criticized for their methodology, but the use of IVIg in this context can still be considered as an option. HCQ again deserves special mention. Several studies have shown that HCQ reduces the risk of cardiac NLS in fetuses at risk and possible recurrences. In view of the multiple beneficial effects of HCQ, it is indicated in all pregnant women with lupus and anti-Ro [11].
\nWomen with SLE have an increased risk of preterm birth. This can occur spontaneously or due to maternal and/or fetal complications, such as a flare of severe lupus, preeclampsia, and FGR. Between 24 and 34 weeks of gestation, the acceleration of fetal lung maturation is essential, with steroids (preferably betamethasone), regardless of any steroid administered previously. Magnesium sulfate when gestational age is <32 weeks, due to its neuroprotective benefits for the fetus, should be administered in cases of severe preeclampsia. The objective in a pregnant patient with SLE should be a spontaneous delivery at term via the vagina. However, available data have revealed that women with SLE undergo a higher cesarean section (>33%, odds ratio (OR) 1.7, confidence interval (CI) 95% 1.6–1.9). Despite this, it is recommended that cesarean sections be reserved only for obstetric indications, due to their additional risk factor for venous thromboembolism (VTE), blood loss and infection, and repercussions for future pregnancies. Intravenous hydrocortisone may be necessary to overcome the physiological stress of labor if long-term oral steroids, which are very common in SLE, have been taken. The standard prophylactic LMWH should be discontinued at the start of spontaneous delivery and the night before induced labor or elective cesarean section. Regional anesthesia (epidural or spinal) can be performed 12 hours after the last dose of LMWH.
\nIn the puerperium, we must control the activity of the SLE for the detection of flare or coexisting preeclampsia. The treatment for postpartum active SLE is similar to that of nonpregnant women. However, the use of some drugs may have effects on the nursing infant. Therefore, the risks and benefits of continuing to breastfeed should be clarified to the nursing mother. All women who received antenatal LMWH should continue using it for 6 weeks after delivery, in a prophylactic dose, since the puerperium is also a period of increased risk of VTE. In patients with SLE, postpartum advice to offer safe contraception is particularly important. Good options are long-acting reversible contraception methods. The use of progestogens is only safe and can become an appropriate option. Contraceptives containing estrogen will not use women with aPL or APS, SLE with moderate to severe flare, lupus nephritis, and some other conditions, such as hypertension, smoking, obesity, or previous VTE, since they increase the risk of VTE. In cases of well-defined SLE with stable and/or mild disease, the use of combined oral contraceptives may be indicated. Contraceptive barrier methods have a high failure rate (15–32%) and, therefore, should not be used as a single method.
\nSLE | systemic lupus erythematosus |
LA | lupus anticoagulant |
aCL | anticardiolipin antibody |
aβ2GPI | anti-β2 glycoprotein I |
aPL | antiphospholipid antibody |
HELLP | hemolysis, elevated liver enzymes, and low platelets |
sFlt-1 | soluble fms-like tyrosine kinase |
PlGF | placental growth factor |
CYC | cyclophosphamide |
LMWH | low molecular weight heparin |
ESR | erythrocyte sedimentation ratio |
MMF | mycophenolate mofetil |
HPA | hypothalamic pituitary axis |
AMH | anti-mulleriana hormone |
GnRH | gonadotrophic hormone receptor |
IUDs | intrauterine devices |
IVF | in vitro fertilization |
OHSS | ovarian hyperstimulation syndrome |
SLEPDAI | SLE pregnancy disease activity index |
LAI-P | lupus activity index pregnancy |
FGR | fetal growth restriction |
NSAIDs | nonsteroidal anti-inflammatory drugs |
ACE | angiotensin-converting enzyme |
DMPA | depot medroxyprogesterone acetate |
SLEDAI | SLE disease activity index |
PHC | primary health center |
FDA | Federal Drug Association |
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