Maternal and newborn health poses one of the greatest health challenges in the developing world. Many low-income countries are now experiencing a demographic and epidemiological transition and changing of lifestyles. Thus, apparent “Western” diseases such as diabetes and obesity have been reaching the Third World countries. There is a paucity of reliable data on diabetes in pregnancy in many low-income countries. Adequate information about maternal and perinatal mortality and morbidity as a consequence of diabetes in pregnancy is scarce. This chapter presents evidence of the magnitude and impact of diabetes in pregnancy. Additionally, we discuss interventions in screening and managing diabetes in pregnancy in these specific patient populations.
Prevalence of gestational diabetes mellitus
Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that begins during pregnancy or is first recognized during pregnancy . Pregestational diabetes is defined as type 1 diabetes or type 2 diabetes present before the onset of pregnancy . Both entities pose great risks to the mother and developing fetus.
The prevalence of type 2 diabetes mellitus (DM) increased almost twofold between 1997 and 2010 in Africa . More recent estimations anticipate that the number of individuals with diabetes will double by the year 2030 . Reports indicate that diabetes will gain more significance around the world in the coming decades, especially in pregnancy . There are vast differences in the prevalence of diabetes in different ethnic groups, with regional prevalence varying from the lowest in Africa (2.4%) to the highest in Europe and North America (7.89%) . Yet, African low-prevalence figures must be interpreted with caution, as the lack of diagnosis resulting from health economic difficulties in many parts of rural Africa has likely caused a surveillance bias.
The current diabetes epidemic affects pregnant women on a large scale, not only in high-income countries but even more so in low-resourced countries . The incidence of GDM has increased dramatically in the past decade in all racial and ethnic groups . GDM influences approximately 7–14% of all pregnant women and is associated with numerous obstetric and neonatal complications, including cesarean delivery , preeclampsia , preterm delivery , fetal macrosomia , and shoulder dystocia .
Although it is well established as a cause for pregnancy complications, studies of the racial and ethnic distribution of GDM have shown significant variation in its prevalence and its epidemiology has not been studied systematically . The actual distinction of GDM, as currently defined, is problematic.
The lack of adequate data on the preexisting, however undiagnosed, diabetes results in a potential bias. The degree of clinical surveillance may have a tremendous impact on the estimated prevalence of GDM in a given population. This is especially true in high-risk populations in which the onset of type 2 DM may even occur at early ages and in low-resourced countries . Furthermore, investigators apply different screening programs and diagnostic criteria for GDM, making comparison among reports extremely difficult.
The tremendous therapeutic progress in diabetes in general and in GDM in particular in the developed world during the last century is not shared to any extent in low-resourced countries, where resources for diabetes management are often lacking, resembling a situation reminiscent of the pre-insulin era.
Racial and ethnical distribution of GDM
The prevalence of GDM varies in direct proportion to the prevalence of type 2 DM in a given population or ethnic group . The reported prevalence of GDM in the United States (US) ranges from 1% to 14%, with 2–5% being the most common reported rate . In a study of the prevalence of diabetes and impaired glucose tolerance (IGT) in diverse patient populations in women between the ages 20 and 39 , the World Health Organization (WHO) Ad Hoc Diabetes Reporting Group noted the lowest rates of diabetes (<1%) in Bantu (Tanzania), Chinese, rural Indian, Sri Lankan, and in some Pacific populations. Low rates of diabetes (about 3–5%) were reported in Italian women and in white, black, and Hispanic women in the US. Rural Fijian Indian and Aboriginal Australian women had 7% prevalence. The highest rates were found in Pima/Papago and Nauruan Indians (14–22%). The prevalence of IGT was <3% in Chinese and Malays, and was >10% in black and Hispanic women in the US, urban Indian women in Tanzania, and Pima and Nauruan Indians and in other Pacific communities. The prevalence of the combined age-stratified rate of both diabetes and IGT ranged from 0% to 36%, with >10% prevalence in one-third of the populations and >30% prevalence in Pima and Nauruan Indians. More importantly, in several populations, the majority of cases diagnosed with diabetes were in fact undiagnosed prior to the survey. Thus, a significant proportion of patients with abnormal glucose tolerance will be missed without screening.
King et al. summarized several reports that had collected data on the prevalence of diabetes in pregnancy . Together with the WHO study, their findings show that for a given population and ethnicity, the risk of GDM reflects the underlying rate of type 2 DM in the specific patient population.
Due to the remarkably varied approaches used, different methods of screenings, various oral and intravenous glucose loads, and different diagnostic criteria, it remains unclear if this marked geographic and racial diversity represents true differences in the prevalence of GDM. For instance, Dooley et al. showed that when comparing the prevalence of GDM in different populations, race as well as obesity must be taken into account. They included 3744 pregnant women who underwent universal screening. The patient population included 39.1% white, 37.7% black, 19.8% Hispanic, and 3.4% Oriental and others. The adjusted relative risk (RR) was increased in black (1.81, 95% confidence interval (CI) 1.13–2.89) and in Hispanic (2.45, 95% CI 1.48–4.04) women. Regarding carbohydrate intolerance, no differences were found. However, when 92 women with GDM under dietary control were analyzed separately, mean birth weight was highest in Hispanic women and lowest in blacks and Orientals. Hence, race had a significant independent impact on neonatal birth weight with maternal percentage ideal body weight a significant covariate. These findings were supported by others, showing that Asian women were more likely to have GDM than Caucasian women (31.7% vs. 14%, p = 0.02) despite their lower body mass index (BMI) .
Recent studies have found higher rates of GDM among Asians, Hispanics, Native Americans, and African Americans as compared to non-Hispanic whites . Asians, with a reported rate of 15%, are more likely to have GDM than any other race, even after controlling for potential confounders such as BMI and socioeconomic status . Distribution variations in the prevalence of GDM by race and ethnicity may be related to genetic factors affecting insulin resistance, lifestyle, diet, sociocultural factors, and health-care access and utilization.
Increased birth weight and insulin levels in the neonate are strongly associated with maternal hyperglycemia, while lifestyle modifications and/or medical treatment may reduce the risk of adverse perinatal outcomes . However, even when applying the same treatment regimens, significant disparities persist in an analysis of adverse perinatal outcomes by race and ethnicity . In a recent study, the authors aimed to determine whether racial or ethnic differences exist in perinatal outcomes in women with GDM among the most common racial/ethnic groups in the US (white, black, Latina/Hispanic, and Asian) . After controlling for maternal age, parity, obesity, gestational age at delivery, weight gain during pregnancy, maternal education, and primary language, an increased risk of primary cesarean delivery, preterm delivery, and fetal demise was found in black women in comparison to other groups. GDM was still most common among Asians and Latinas/Hispanics.
Understanding the racial and ethnic disparities in GDM diagnosis, management, and outcomes is thus a substantial step towards the resolution of the prevalence differences and widespread improvement of maternal and child health.
Racial and ethnical distribution of GDM
The prevalence of GDM varies in direct proportion to the prevalence of type 2 DM in a given population or ethnic group . The reported prevalence of GDM in the United States (US) ranges from 1% to 14%, with 2–5% being the most common reported rate . In a study of the prevalence of diabetes and impaired glucose tolerance (IGT) in diverse patient populations in women between the ages 20 and 39 , the World Health Organization (WHO) Ad Hoc Diabetes Reporting Group noted the lowest rates of diabetes (<1%) in Bantu (Tanzania), Chinese, rural Indian, Sri Lankan, and in some Pacific populations. Low rates of diabetes (about 3–5%) were reported in Italian women and in white, black, and Hispanic women in the US. Rural Fijian Indian and Aboriginal Australian women had 7% prevalence. The highest rates were found in Pima/Papago and Nauruan Indians (14–22%). The prevalence of IGT was <3% in Chinese and Malays, and was >10% in black and Hispanic women in the US, urban Indian women in Tanzania, and Pima and Nauruan Indians and in other Pacific communities. The prevalence of the combined age-stratified rate of both diabetes and IGT ranged from 0% to 36%, with >10% prevalence in one-third of the populations and >30% prevalence in Pima and Nauruan Indians. More importantly, in several populations, the majority of cases diagnosed with diabetes were in fact undiagnosed prior to the survey. Thus, a significant proportion of patients with abnormal glucose tolerance will be missed without screening.
King et al. summarized several reports that had collected data on the prevalence of diabetes in pregnancy . Together with the WHO study, their findings show that for a given population and ethnicity, the risk of GDM reflects the underlying rate of type 2 DM in the specific patient population.
Due to the remarkably varied approaches used, different methods of screenings, various oral and intravenous glucose loads, and different diagnostic criteria, it remains unclear if this marked geographic and racial diversity represents true differences in the prevalence of GDM. For instance, Dooley et al. showed that when comparing the prevalence of GDM in different populations, race as well as obesity must be taken into account. They included 3744 pregnant women who underwent universal screening. The patient population included 39.1% white, 37.7% black, 19.8% Hispanic, and 3.4% Oriental and others. The adjusted relative risk (RR) was increased in black (1.81, 95% confidence interval (CI) 1.13–2.89) and in Hispanic (2.45, 95% CI 1.48–4.04) women. Regarding carbohydrate intolerance, no differences were found. However, when 92 women with GDM under dietary control were analyzed separately, mean birth weight was highest in Hispanic women and lowest in blacks and Orientals. Hence, race had a significant independent impact on neonatal birth weight with maternal percentage ideal body weight a significant covariate. These findings were supported by others, showing that Asian women were more likely to have GDM than Caucasian women (31.7% vs. 14%, p = 0.02) despite their lower body mass index (BMI) .
Recent studies have found higher rates of GDM among Asians, Hispanics, Native Americans, and African Americans as compared to non-Hispanic whites . Asians, with a reported rate of 15%, are more likely to have GDM than any other race, even after controlling for potential confounders such as BMI and socioeconomic status . Distribution variations in the prevalence of GDM by race and ethnicity may be related to genetic factors affecting insulin resistance, lifestyle, diet, sociocultural factors, and health-care access and utilization.
Increased birth weight and insulin levels in the neonate are strongly associated with maternal hyperglycemia, while lifestyle modifications and/or medical treatment may reduce the risk of adverse perinatal outcomes . However, even when applying the same treatment regimens, significant disparities persist in an analysis of adverse perinatal outcomes by race and ethnicity . In a recent study, the authors aimed to determine whether racial or ethnic differences exist in perinatal outcomes in women with GDM among the most common racial/ethnic groups in the US (white, black, Latina/Hispanic, and Asian) . After controlling for maternal age, parity, obesity, gestational age at delivery, weight gain during pregnancy, maternal education, and primary language, an increased risk of primary cesarean delivery, preterm delivery, and fetal demise was found in black women in comparison to other groups. GDM was still most common among Asians and Latinas/Hispanics.
Understanding the racial and ethnic disparities in GDM diagnosis, management, and outcomes is thus a substantial step towards the resolution of the prevalence differences and widespread improvement of maternal and child health.
Etiology
Sociocultural perspective
Gender studies present the East African woman as a complex and dominant individual. They have central roles as mothers, workers, citizens, and members of families and communities . Since adolescence, the women are focused on reproduction and are educated accordingly. According to the female role in East African society, being childless means expulsion from the local community and stigmatization . Due to these social and cultural pressures, childbearing even in later stages of life is common. The impact of diabetes draws various social implications on the local African woman. In cases of diabetes in pregnancy, the children born with birth defects or congenital disease customarily become a female responsibility, with all the attendant implications. In addition, poor obstetric outcomes in such pregnancies may lead to a desire for “replacement” children. This, in turn, motivates high parity and its adverse sequel. Additionally, both GDM and pregestational diabetes increase the probability of intrauterine fetal death, macrosomia followed by shoulder dystocia, uterine rupture, and postpartum hemorrhage . Finally, it is well established that untreated GDM causes late-onset diabetes leading to related complications in later stages of life and negatively impacting women’s life expectancy. GDM leads to a higher prevalence of diabetes in the offspring of mothers who were affected by diabetes in pregnancy and, in turn, burdens future female generations .
Overnutrition
The global trend of an increased prevalence of diabetes in low-resourced populations with the subsequent increase of GDM is closely linked to the increase in obesity . Africans, especially in urban settings, are experiencing rapid demographic and epidemiological transitions, changing diets and lifestyles encouraging urban drift and transnational migration. This is characterized by an enormous rise in noncommunicable diseases and by the westernization of the population . In the past decade, pregnancy in women with type 2 DM has become common even among populations previously rarely affected .
Malnutrition
Biological and environmental factors in rural areas of developing countries, in combination with malnutrition, cause metabolic alterations distinct from those seen in developed countries. Malnutrition concomitant with physical work and iron and protein insufficiencies contribute to the high prevalence of low-birth-weight newborns . The pancreas appears to be sensitive to maternal anemia and infectious diseases. In both in vitro studies and in human studies, a reduced number of pancreatic beta cells is noted in children who were small for gestational age at birth, suggesting a reduced vascularization and replication rate caused by maternal diabetes or malnutrition .
Diabetes in pregnancy and infectious diseases, concomitant with malnutrition, adversely impact maternal metabolism and induce a catabolic state and an increased risk of ketoacidotic complications during pregnancy . Hence, basal glucose levels are most likely to be lower in the parturient in low-income countries compared with their counterparts in high-income countries.
Early programming of adult diseases – thrifty genotypes and thrifty phenotypes
In recent decades, the incidence of type 2 DM has dramatically increased worldwide due to changes in lifestyle, from those of hunters, gatherers, and farmers to a contemporary pattern mainly characterized by sedentary occupations and high-energy fuel resources . As a result, noninfectious diseases such as hypertension, non-insulin-dependent DM and cardiovascular diseases have emerged as the major causes of morbidity and mortality both in developing and in developed countries . Currently, the highest prevalence of type 2 DM is found in populations that have undergone rapid alterations in lifestyle, such as Australian Aborigines, Native Americans, Pacific islanders, and some migrant populations such as the Asian Indians .
In 1962, Neel et al. proposed the “thrifty genotype” hypothesis as a preliminary explanation for this observation . In order to persist through centuries of evolution, and in the face of the obvious and strong genetic selection against this condition, the diabetogenic genes must have conferred a survival advantage in times of nutritional deprivation; yet they were detrimental at times of adequate nutrition or overnutrition. In the late 1980s, Barker et al. observed that the geographical distribution of heart disease was more closely related to a person’s place of birth rather than to the current residence . This suggests that early life events can cause permanent changes in physiology that, depending on the environment, may later entail a predisposition to disease. In the 1990s, the “thrifty phenotype” hypothesis was suggested by Hales and Barker as a probable etiology of type 2 diabetes . They claimed that adverse mechanisms of nutritional thrift on the growing individual are imposed by poor fetal and poor early infant nutrition. The thrifty phenotype hypothesis proposes that subsequent development of type 2 diabetes and the metabolic syndrome result from poor nutrition in early life, which produces permanent changes in glucose–insulin metabolism. During the period, the individual persists in the undernourished state, the physiological state being appropriate. However, when the early adaptations that have been invoked to survive under restricted nutrient supply are later faced with conditions of affluence and overabundance, the physiology is disturbed and overwhelmed, sequentially leading to the occurrence of disease .
It is assumed that a combination of the thrifty genotype and the thrifty phenotype amplifies the predisposition of populations in developing countries to acquire diseases of affluence. This phenomenon is particularly apparent in countries undergoing a rapid economic and nutritional transition, or in peoples migrating from poor to wealthy countries . Observations in support of this assumption involve, for example, the increased susceptibility of Asians to diabetes and of Africans to hypertension .
Associations between maternal nutrient restriction during pregnancy and lactation were demonstrated in animal models. Feeding a low-protein diet in rat pregnancy resulted in deviant fetal growth and low birth weight. The offspring of rats fed low-protein diets exhibited metabolic and physiological disturbances, and were consistently found to have high blood pressure from early postnatal life. Fetal exposure to maternally derived glucocorticoids plays a key role in the programming mechanism, in terms that secondary to this activity, the fetal hypothalamic–pituitary–adrenal axis may stimulate rennin–angiotensin system activity, resulting in increased vascular resistance and hypertension .
Yajnik et al. from Pune, India, studied the body size and cord blood leptin and insulin concentrations in newborn urban Indians (Pune, India) and white Caucasians (London, UK). They used anthropometric measurements of babies to describe their morphology at birth. Indian babies were much smaller than white Caucasian babies in all aspects apart from measurements of body fat and particularly central fat as judged by the subscapular skinfold thickness . They described these babies as having the “thin–fat” baby syndrome claiming it showed that the excess visceral adiposity in most Asian adults can be traced back to the neonatal phase. In the babies of urban mothers in Pune, cord blood insulin levels appeared to be higher when compared to the white Caucasian babies and were correlated with subscapular skinfold thickness . Later in childhood, these “thin–fat” Indian babies have substantial impaired indices of insulin sensitivity, which inversely correlated with birth weight . These studies provided the first solid data to confirm the claim that the people living in developing countries are prone to suffer the greatest effects of early programming.
Fetal and early postnatal undernutrition can provoke metabolic adaptations that affect variables such as hepatic enzyme profiles , lipoprotein profiles , clotting factor production , organ glucose uptake , renal solute handling , and endocrine adaptations that affect the hypothalamic–pituitary–adrenal axis , insulin signaling , and leptin levels . These changes map onto health outcomes such as coronary heart disease, stroke, type 2 diabetes, and the metabolic syndrome, all of which have been shown to be increased in low-birth-weight neonates .
Finally, there have been studies demonstrating that neonates randomized to different forms of feeding in early life show profound later sequel, even when the time interval of randomization was extremely short . An abundance of evidence in support of this theory has since emerged .
Maternal and perinatal mortality
There is a lack of reliable data on diabetes in pregnancy in many low-income countries. Adequate information about maternal and perinatal mortality (PNM) as a consequence of diabetes in pregnancy is scarcely reported. Hence, diabetes in pregnancy should be further investigated and its impact on maternal mortality rates (MMRs) should be evaluated and considered.
In 2004, the WHO estimated that 529,000 maternal deaths occurred in 2000 worldwide: 251,000 in Africa and 253,000 in Asia, with about 4% (22,000) occurring in Latin America and the Caribbean, and <1% (2500) in the more developed regions of the world . In terms of the MMR, the world figure is estimated to be 400 per 100,000 live births. Stratified by region, the MMR was highest in Africa (830), followed by Asia (330), Oceania (240), Latin America and the Caribbean (190), and the developed countries (20).
In 2010, a systemic analysis estimated maternal deaths worldwide decreased from 526,300 in 1980 to 342,900 in 2008. The global MMR decreased from 422 in 1980 to 251 per 100,000 live births in 2008. The global MMR declined at a rate of 1.3% since 1990. During the years 1990–2008, the rates of yearly decline in the MMR varied between countries, from 8.8% in the Maldives to an increase of 5.5% in Zimbabwe. In 2008, >50% of all maternal deaths occurred in only six countries, all low-income countries (India, Nigeria, Pakistan, Afghanistan, Ethiopia, and the Democratic Republic of the Congo) .
According to the Latin-American & Caribbean Regional Office of UNICEF , the risk of maternal mortality in the developing compared with the developed world in 1990 was 1:48 and 1:1800, respectively, with an incidence of 1:140 for South America. Even though the MMR is apparently low, it has remained relatively stable during the past decade. For example, the MMR in Argentina was 5.2 in 1990, 4.4 in 1995, 3.5 in 2000, and 4.0 in 2004, which shows it has been very difficult to lower . The reported MMR incidence in the region was 190 per 100,000 live births, with a great variation between countries . According to the publication of UNICEF in 2005, while in Brazil, Uruguay, Chile, Cuba, Santa Lucia, Argentina, and Costa Rica the MMR was <50 per 100,000, in other countries such as Peru, Bolivia, and Haiti the MMR was >150 per 100,000.
Coetzee et al. found a PNM rate of 14 per 1000 in African patients with GDM. They also reported that mothers who had prenatal care with GDM, but whose diabetes was treated for <2 weeks, had a PNM of 264 per 1000 . From their departmental reports, the overall PNM is 30 per 1000. Nondiabetic mothers who had received no prenatal care had a PNM of 94 per 1000. Mothers with pregestational type 2 diabetes who were treated had a PNM of 70 per 1000, while “untreated” type 2 diabetes had a PNM of 313 per 1000. Hence, it is obvious that untreated diabetes poses a greater threat of PNM than having no prenatal care. Additionally, in both treated and untreated women with diabetes, the prevalence of neonatal hypoglycemia, macrosomia, jaundice, and anomalies was increased.
In addition to common diabetic complications such as retinopathy, nephropathy, and neuropathy in women with pregestational diabetes, infectious morbidity is significantly more frequent than in healthy women. There is a correlation between the frequency of infections and poor metabolic control . Additionally, preeclampsia, which occurs in 20% of diabetic pregnant women (three times more frequently than in healthy pregnant women), significantly increases perinatal and maternal mortality and morbidity .
The major cause of maternal complications and subsequent deaths in low-resourced countries as those in East Africa seems to be the delay in arrival at health-care centers and hospitals . Apart from the lack of financial means and living far from health centers, the low educational level often prevents a timely and potentially lifesaving presentation at health facilities especially for women in the rural areas .
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