COMMENTARY

May/June 2004: Preterm Birth as a Social Disease

Ursula Snyder, PhD

Disclosures

July 06, 2004

Premature birth is now the most common, serious, and costly infant health problem facing our nation.

Jennifer L. Howse,PhD, President of the March of Dimes

Spontaneous preterm birth is a common outcome of a broad combination of medical and social factors. In fact, it may be said to be a social disease: it happens much more frequently when the mother is poor, has a low educational level, is isolated, single or too young...National data are unequivocal on this major point: preterm birth is closely related to social class...

Emile Papiernik, MD, L'Universite Rene Descartes Paris V, Maternite de Port Royal

The progress of neonatal medicine has been so spectacular, and the failure to prevent preterm deliveries so disappointing, that there is a risk that high rates of preterm births will be seen as unavoidable.

Pierre Buekens, MD, PhD, University of North Carolina, Chapel Hill
Mark Klebanoff, MD, NICCHD, National Institutes of Health

Preterm birth (together with low birth weight) has been described as the most profound problem of children today. It's a topic many readers have suggested we cover in a CME program, and we are hoping to have one by the end of the year. In the meantime, I have compiled a series of abstract collections that highlight recent research on preterm labor from pathogenesis to intervention:

MEDLINE Abstracts: Preterm Labor - Pathogenesis

MEDLINE Abstracts: Preterm Birth - Epidemiology and Prevention

MEDLINE Abstracts: Risk Factors for Preterm Labor and Delivery

MEDLINE Abstracts: Predicting Preterm Labor

MEDLINE Abstracts: Intervention in Preterm Labor

Recent data from the United States National Center of Health Statistics reveal that 2002 marked a record high in the number of preterm births -- 480,812.[1] This represents a 13% increase over a decade. A March of Dimes summary of these data notes that some states had increases of > 30% (Hawaii, 33%; Maine, 35%; Massachusetts, 38%; Montana, 30%; Nebraska, 34%; New Hampshire, 30%).[2] Notably, the District of Columbia had a 22% decrease -- the only decrease for the decade. The year 2002 also marked the largest percentage increase in preterm births among white women. Two major causes of preterm birth are advanced maternal age and multifetal pregnancies conceived by assisted reproductive technologies (ART) (ie, the use of ovulation-induction drugs and in vitro fertilization).[3]

Russell and colleagues,[4] from the March of Dimes, have examined the change in the epidemiology of multiple births in the United States by race, maternal age, and region. Between 1980 and 1999, the greatest increases in multiple births were associated with white race, advanced maternal age, and residence in the Northeast.

Another nationwide review[5] of multifetal (twins and triplets) pregnancies in women and perinatal outcomes between 1995 and 1997 showed that women with multiple gestations tended to be older, non-Hispanic white, better educated, married, and nulliparous. They also tended have earlier and more frequent prenatal care. Multiple gestations in older women were attributed to the increasing use of ART. But this study also found that older women with higher socioeconomic status did not have a higher risk of poor perinatal outcomes than younger women; whereas, in women with lower socioeconomic status, older age was associated with higher risks of poor perinatal outcomes in twin pregnancy.

Two other factors are significantly and independently associated with preterm birth: maternal stress and maternal urogenital tract infection. Both of these are more prevalent among socially disadvantaged women.[6,7] And despite the trend mentioned above, preterm birth in the United States at this point still disproportionately affects socially disadvantaged women and minority women, especially black women.[6,7,8,9,10,11,12] On the basis of 2001 data,[12] the rate of preterm birth for African Americans was 17.6%, followed by 12.8% for Native Americans, 11.4% for Hispanics, 10. 6% for whites, and 10.2% for Asians. Moreover, for black mothers alone, complications of prematurity and low birth weight are the leading causes of infant mortality. The most recent data we have indicate that the cause-specific infant mortality rate for low birth weight is 4 times higher for blacks than for whites.[13] Generally, in the United States, a black infant is more than twice as likely to die before 1 year of age than a white infant.[14] A point of note is that the results of 1 study suggest that the birth-weight patterns of infants of African-born black women and US-born white women are more closely related to one another than to those of infants born to US-born black women.[15]

As the editorial note in the Centers for Disease Control and Prevention (CDC) report on infant mortality and low birth weight among black and white infants states:

 

The specific causes for increased low birth weight and preterm delivery might differ for blacks and whites. The etiology of black-white disparities in low birth weight is complex and is not explained entirely by demographic risk factors such as maternal age, education, or income... Factors that might contribute to the disparity include racial differences in maternal medical conditions, stress, lack of social support, bacterial vaginosis, previous preterm delivery, and maternal health experiences that might be unique to black women...

In this regard, some interesting and important research on the causes of preterm birth is focusing on maternal stress and the role of placental corticotropin-releasing hormone (CRH) in mediating pathophysiologic events in the endocrine and immune systems during pregnancy. Some of this work is described in the 2001 supplement to the journal Paediatric and Perinatal Epidemiology. Wadhwa and colleagues[6] present a biobehavioral model of maternal stress as an independent risk factor for spontaneous preterm delivery by its effects on one or both of 2 physiologic pathways:

 

a neuroendocrine pathway, wherein maternal stress may ultimately result in premature and/or greater degree of activation of the maternal-placental-fetal endocrine systems that promote parturition, and (b) an immune/inflammatory pathway, wherein maternal stress may modulate characteristics of systemic and local (placental-decidual) immunity to increase susceptibility to intrauterine and fetal infectious-inflammatory processes and thereby promote parturition through proinflammatory mechanisms...Moreover, because neuroendocrine and immune processes extensively cross-regulate one another...exposure to both high levels of chronic stress and infectious pathogens may produce an interaction and multiplicative effect in terms of their combined risk for preterm birth. Finally, ... the effects of maternal stress [may be] modulated by the nature, duration and timing of occurrence of stress during gestation...

Most importantly, Wadhwa and colleagues suggest that a biobehavioral approach will stimulate exploration of "new questions" in a more comprehensive way. Indeed, Rich-Edwards and colleagues[10] are conducting a longitudinal study of 6000 pregnant women and their children living in the Boston area, and they are specifically examining maternal experiences of racism and violence in relation to preterm birth. They write:

 

It may be that the standard set of socioeconomic factors fails to explain the full meaning of being African-American. For many, experiences of being discriminated against as a person of color are everyday occurrences at once painful and threatening. This chronic strain may have an effect more insidious and powerful than is captured by our customary models...
The hypothesis that a woman's experience of chronic threat before pregnancy affects pregnancy outcome rests on the concept of allostatic load.... [Allostasis] refers to the ability of the body to achieve stability through change, 'such that the autonomic nervous system, the hypothalamic-pituitary-adrenal (HPA) axis, and cardiovascular, metabolic, and immune systems protect the body by responding to internal and external stress. The price of this accommodation to stress can be allostatic load, which is the wear-and-tear from chronic overactivity or underactivity of the allostatic system'. We theorize that frequent stress whether concurrent, feared, or remembered, increases allostatic load. Thus, we propose that a woman's chronic exposure to racism or violence creates an allostatic load that imprints itself upon her HPA axis prior to conception, altering the endocrine milieu in which the placenta is established, and potentially changing the hormonal interaction between fetus, placenta and mother.

And, Kramer and colleagues[7] are looking at the role of chronic and acute psychosocial stressors, the psychological distress caused by the stressors and the effect on placental CRH and changes in sexual behavior or increased susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking, drug use, and decidual vasculopathy. They are also investigating a possible gene-environment interaction. The gene is methylenetetrahydrofolate reductase, for which there is a highly prevalent polymorphism. Women with this polymorphism who have low folate intake from the diet and prenatal vitamin supplements may be at higher risk for hyperhomocysteinemia and, consequently, decidual vasculopathy.

In their commentary for the Paediatric and Perinatal Epidemiology supplement, Buekens and Klebanoff[9] note that this work comes out of a need for a new research agenda -- one that focuses on social and biological mechanisms of prematurity, because past work that focused more on risk factors and interventions has not been fruitful. After more than a quarter of a century of research, "we simply do not know how to prevent the problem in an effective way."[16] Buekens and Klebanoff also note the need to consider broader contextual factors, such as neighborhoods and healthcare systems and social policy and poverty. A recent study of Chicago neighborhoods,[17] for example, showed that neighborhood-level factors are significantly associated with infant birth weight. Mean birth weight decreased significantly as the neighborhood level of economic disadvantage increased -- but only for black mothers. By contrast, a significant positive association was found between perceived levels of neighborhood social support and infant birth weight -- but only for white mothers.

Let's look at access to healthcare in the United States. On the basis of 2001 census data, only 32.7% of the female population was covered through private health insurance or Medicaid. In the United States today, 43.6 million people lack any kind of insurance; some 36 million, many of whom are not eligible for Medicare or Medicaid, have no access to healthcare, according to a study conducted by the National Association of Community Health Centers.[18] The increase in people without insurance in 2002 (from 14.6% to 15.2% of the population) is the largest in a decade. And, just recently, Families USA reported that 82 million Americans -- that's 1 in 3 -- younger than 65 years of age lacked health insurance for all or part of the 2-year period from 2002 to 2003.[19] In addition, 27 million of these were uninsured children (< 18 yrs) -- 36.7% of all US children. The racial disparity with respect to lacking insurance is marked. Nearly 60% of Hispanics were uninsured, about 43% of blacks were uninsured, and 24% of whites were uninsured. Moreover, about 14 million low-income adults do not qualify for public health insurance programs, according to Families USA[20]; in 36 states, parents with poverty level incomes (below $15,260 for a family of 3) cannot qualify for public health insurance, and in 42 states, adults without children are ineligible for Medicaid regardless of their income, unless they are severely disabled.

Poverty and income inequality in the United States are increasing, and, according to the February 2004 report by American's for Democratic Action, Inc.[21]:

 

A total of 34.6 million Americans, 12.1% of the population in 2002, live in poverty. One-third of America's poor are White, with a 10% poverty rate; at 20%, the rate for African Americans and Hispanics is twice that of Whites. Black and Hispanic median family income is 37% below the median income of White families. Nationally, one out of six children, 11.7 million, live in poverty. One out of every three Black and Hispanic children lives in poverty.
Many poor people are working people, and many of them work full-time, year-round but don't earn enough to lift themselves and their families out of poverty. Of 8.5 million people in poverty who did work in 2002, there were 2.6 million on the job full-time, year-round. Another 6.0 million worked full time for part of the year, but remained in poverty. With the minimum wage of $5.15 an hour enacted in September 1997, the $10,700 annual earnings of a minimum wage worker employed full-time, year-round is still be $3,628 less than the three-person family poverty line, and $7,604 below the four-person family poverty threshold.

Income inequality in the United States is greater than in other major industrialized countries (eg, Australia, Canada, Europe). And the report further notes that "because of the extremely uneven distribution of the nation's economic growth from 1980 through the 1990s, income inequality widened so greatly that the current gap between the richest and the poorest is larger than it has been since the Depression years of the 1930s." Income inequality is increasingly being studied as a social determinant of health. For example, a recently published analysis of 1990 census data and cardiovascular disease mortality rates by Massing and colleagues[22] found that in the United States, county income was inversely related and income inequality was directly related to CVD, coronary heart disease, and stroke mortality. Another recent study[23] investigated county-level income inequality and pregnancy spacing in a welfare-recipient cohort in Washington State. The researchers report that income inequality seems to be associated with time-dependent risk of a subsequent pregnancy for women aged ≥26 years at the index birth. A short interpregnancy interval (< 6 months) is an independent risk factor for preterm delivery and neonatal death in the second birth.[24]

Consider this: Europe has half the rate of preterm birth of the United States. Europe also has, to a much greater extent, broad healthcare coverage and social protection. Dr. Emile Papiernik,[11] a leading researcher in the field of preterm birth, has discussed the role of healthcare and social policy in Europe in the prevention of preterm birth. In the 1930s, a multinational study in Europe established that preterm delivery was a significant factor in infant mortality within the first week of life.[11,25] The study identified social factors but especially highlighted the relation between preterm birth and physical labor (inside and outside the home), and as a result, the authors recommended a systematic maternity leave program for pregnant women. The study was published in 1933, and only 2 years later, Sweden took up the cause. Dr. Papiernik writes:

 

Sweden began granting such maternity leave for all pregnant women working outside the home in 1935, and other Scandinavian countries soon followed suit. Women who went on leave received financial compensation and job protection. Maternity leave was mandatory for all women and, along with free prenatal care, was an important part of the European 'System for Protection of Mother and Child.' Since 1945, all European countries have instituted paid maternity leaves for the specific purpose of preventing preterm birth. Leave begins during the last 6-8 weeks of pregnancy in Belgium, France, Germany, Ireland, Italy and The Netherlands, 10 weeks before the due date in Sweden, and 12 weeks in Norway and the UK. All countries provide sick leave in addition to maternity leave, for as long as necessary during pregnancy, although the proportion of salary received for sick leave is less than that given for maternity leave. In Belgium, Bulgaria, Germany, The Netherlands and Poland, women receive 100% of their salaries during maternity leave. The corresponding figure in Czechoslovakia, Denmark, and Sweden is 90%, and in Italy and Greece, about two-thirds. In the United States of America, federal law recently allowed pregnant women to demand a leave during pregnancy, but no nation-wide law guarantees them any payment for this "time off"...

***

In 2002, the 1st International Preterm Labour Congress was held in Montreux, Switzerland. The proceedings have been published in a supplement to the British Journal of Obstetrics and Gynecology. In his commentary on the meeting, Dr. Ronald Lamont, "Looking to the Future" supplement editor, notes: "this meeting has been very clinically and obstetrically orientated, in future we will need to involve epidemiologists, neonatologists, microbiologists, genito-urinary medicine physicians, immunologists, geneticists, physiologists, and endocrinologists." In a section "Proactive approach," he further writes:

 

In the long-term, it will be helpful to reduce the incidence of spontaneous preterm labour and preterm birth by reducing risk factors...It would be helpful to improve sociobiological status, but it has to be recognized that societal changes will take tens of years to accomplish.

Perhaps, but where there is a will there is a way, as the saying goes. Sweden takes care of its women and children. It has one of the lowest rates of infant mortality in the world (with an estimated 2.77 deaths per 1000 live births for 2004; only Singapore's rate is lower, at 2.28).[26] By contrast, US infant mortality is estimated to be 6.63 in 2004 ( it ranks 40th among 225 countries). A future that would see reduced rates of preterm birth and infant mortality in the United States clearly demands more from us than an international gathering of Dr. Lamont's medical specialists and scientists. (As an aside, it is interesting that he did not mention sociologists, psychologists, or psychiatrists, and a funny little remark in a paper in the BJOG supplement was the following: ...a psychiatrist in Saint-Justine Hospital was able to stop preterm labour in a substantial fraction of women from all social backgrounds after a 40-minute interview.[8]). Dr. Papiernik[11] says:

 

At first glance, social background does not seem amenable to any preventative measures or policies: the clinician cannot change the social class to which a pregnant woman belongs. Such a resigned approach, however, is an inappropriate response to the problem....
The social factors responsible for preterm birth have not disappeared, but their role has been diminished in all countries that provide comprehensive prenatal care, with free access to care, a high number of prenatal visits, legal protection against excessive physical work during pregnancy, help in case of isolation, and shelter for very vulnerable women, single women, and teenagers.

The United States hasn't chosen this route. Instead, it provides more neonatologists and neonatal intensive care beds per person than Australia, Canada, or the United Kingdom.[27]

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