Premature Delivery and the Millennium Development Goal

Abstract

Worldwide, approximately 15 million babies (1 in 10) are born prematurely each year. Prematurity is the leading cause of death among newborns, accounting for 1 million deaths per year, and, after pneumonia, is the second leading cause of death in children under age 5 years. Newborns who do survive preterm delivery (PTD) struggle with visual, auditory, and learning disabilities. In order to reach the fourth Millennium Development Goal (MDG-4) of reducing the mortality rate in children under age 5 years by two-thirds between 1990 and 2015, there must be significantly fewer PTDs. In high-income nations, 50% of babies born at 24 weeks survive, whereas in low-resource nations, this survival rate is not achieved until 32 weeks of gestation. Over 90% of babies born in low-resource settings before 28 weeks die in the first few days of life (< 10% die in high-income nations), a 10:90 survival gap. Over 60% of PTDs worldwide occur in Sub-Saharan Africa and South Asia. Risk factors for PTD include adolescent pregnancy, short interval between births, poor prepregnancy weight (very low or high body mass index), chronic diseases (diabetes and hypertension), infectious disease, substance abuse, cervical incompetence, and poor psychological health. Thus, a commitment to improving maternal health and the quality of prenatal care is necessary to achieve the MDG-4.

Preterm delivery (PTD) has gained significant attention over the past 4 years. In 2008, the World Health Organization (WHO) published estimates of PTD,¹ and The Lancet published a series on preterm birth (http://www.thelancet.com/series/preterm-birth). In 2009, the March of Dimes White Paper on Preterm Birth estimated that 13 million PTDs occurred in 2005.² The Global Alliance to Prevent Prematurity and Stillbirth was launched in 2009.³ Born Too Soon: The Global Action Report on Preterm Birth was recently released by The March of Dimes; the Partnership for Maternal, Newborn and Child Health; Save the Children; and WHO.⁴ That report reviews the issues surrounding PTD and its effect on countries, assessing existing interventions and recommendations for research and areas where innovative cost-effective efforts could be made to significantly decrease PTD. Their review of the data and analyses show that deaths from PTD can be reduced by over 75% without neonatal intensive care units.

The WHO defines PTD as delivery before 37 weeks of gestation, which is reported in completed weeks. PTD is further divided into subcategories: < 28 weeks is defined as extremely preterm; 28 to 32 weeks is very preterm; and 32 to 37 weeks is moderate to late preterm (Table 1). These definitions rely on the baby’s gestational age rather than weight, allowing a distinction between being born too early (prematurity) and being born too small (small for gestational age).⁵ It is challenging to determine accurate gestational age in low-resource settings because the mother’s last menstrual period is rarely remembered. As a result, birth weight (not gestational age) has often been used as a proxy measure for maturity, thus perpetuating inaccuracy in data.

Table 1.

Subcategories of Preterm Birth Based on Weeks of Gestational Age

Extremely preterm (< 28 weeks)

Very preterm (28 to < 32 weeks)

Moderate to late preterm (32 to < 37 weeks)

Births at 37 to 39 weeks still have suboptimal outcomes, and induction or cesarean birth should not be planned before 39 completed weeks unless medically indicated.

Reprinted with permission from the World Health Organization.⁴

Demographics and Trends

The rate of PTD is rising in most countries. Reasons include better data collection, increased maternal age, the growing prevalence of chronic diseases, more multiple gestations resulting from infertility treatments, and more frequent preterm cesarean deliveries. Over 60% of PTDs occur in Sub-Saharan Africa and Southern Asia (Figure 1). The countries with the highest annual number of preterm births are India (3.52 million), China (1.17 million), Nigeria (773,600), Pakistan (748,100), Indonesia (675,700), and the United States (517,400). The countries with the highest rates of preterm births for every 100 births are Malawi (18.1), Comoros (16.7), Zimbabwe (16.6), Equatorial Guinea (16.5), and Mozambique (16.4). In contrast, countries with the lowest rates of preterm birth are Belarus (4.1), Ecuador (5.1), Latvia (5.3), Finland (5.5), and Croatia (5.5).⁴

Figure 1.

Preterm births by gestational age and region for year 2010 based on Millennium Development Goal regions. Reprinted with permission from the World Health Organization.⁴

There has been progress toward reaching the fourth Millennium Development Goal (MDG-4) in the area of child survival. Thirty-five countries currently appear to be on track to achieve the goal by 2015. The biggest barrier to progress on MDG-4 has been the inability to reduce the number of neonatal deaths and deaths from prematurity.³ Programs have mainly focused on reducing deaths after the first month of life by targeting diseases such as pneumonia, diarrhea, malaria, and vaccine-preventable diseases, leading to a steady decline in mortality rates in children under age 5 years.⁶ As a result, an increasing proportion of deaths in children under age 5 years are neonatal (from 37% in 1990 to 40% in 2010).³ Although the deaths from PTDs are terrible losses, the children who survive suffer serious long-term complications, such as neurological delays and hearing and visual impairments, which overwhelm an already strained health system (Table 2).

Table 2.

Long-Term Impact of Preterm Birth on Survivors

Visual impairment

Blindness or high myopia after retinopathy of prematurity

Increased hypermetropia and myopia (25%)

Hearing impairment (5%–10%)

Chronic lung disease of prematurity (40%)

Reduced lung function

Increased rates of asthma

Long-term poor cardiovascular health and noncommunicable disease

Increased blood pressure

Growth failure in infancy, accelerated weight gain in adolescence

Neurodevelopmental/behavioral effects

Specific learning impairments, dyslexia, reduced academic achievement

Moderate/severe cognitive impairment

Motor impairment

Cerebral palsy

Psychiatric/behavioral sequelae

Attention deficit hyperactivity disorder

Increased anxiety and depression

Adapted with permission from the World Health Organization.⁴

Risk Factors

There are many factors that contribute to the risk of PTD (Table 3). A prior PTD is the strongest risk factor for recurrent PTD, and yet most women with a history of PTD will deliver at term.^7,8 After one PTD, the frequency of recurrence is 14% to 22%; it rises to 28% to 42% after two PTDs, and to 67% after three PTDs.^9,10 Just one full-term delivery will decrease this risk; however, if a woman has no history of PTD, her risk in subsequent pregnancies is < 0.8%.¹¹

Table 3.

Risk Factors for Preterm Birth

Previous preterm delivery

Uterine distension: multiple fetal gestation, polyhydramnios, uterine anomaly, leiomyoma

Cervical trauma: diethylstilbestrol-induced changes in uterus, history of second-trimester abortion, history of cervical surgery, premature cervical dilatation or effacement (short cervical length)

Infection: sexually transmitted infections, pyelonephritis, appendicitis, pneumonia, systemic infection, bacteriuria, periodontal disease

Placental issue: placenta previa, placental abruption, recurrent vaginal bleeding

Abdominal surgery during pregnancy

Fetal anomaly

Chronic diseases: hypertension, diabetes, thyroid, anemia (hemoglobin < 10 g/dL)

Demographic: maternal age (< 18 y or > 40 y), black race, genotype

Inadequate preconception and prenatal care, inadequate family planning

Social: poor nutrition and low body mass index, low socioeconomic status, smoking, substance abuse

Psychosocial: anxiety, depression, stress

Occupational: physical exertion, standing

Data from Robinson and Norwitz.¹¹

Multiple gestations directly increase the risk of PTD through higher intrauterine volume, uterine distension, and cervical incompetence. Given the growing frequency of infertility treatments, the higher number of multiple gestations has played a significant role in the incidence of PTD. In developed nations, 17% of births occur before 37 weeks of gestation, and 23% occur in less than 32 weeks of gestation.¹²

Women who have had a history of vaginal bleeding, abruption, and placenta previa are at an increased risk of PTD. A shortened cervix found during pregnancy, prior cervical surgery, uterine malformations, and large uterine leiomyomas are all associated with PTD as well.¹¹

Infections are known to play a significant role in PTDs. Chorioamnionitis has been detected by pathologists in the placentas of 20% to 75% of patients with PTD and by placental culture growth in 30% to 60% of such patients.¹³ Untreated asymptomatic bacteriuria and urinary tract infections have also been known to contribute to PTD. Vaginal infections including, Group B streptococci, Chlamydia trachomatis, bacterial vaginosis, Neisseria gonorrhea, syphilis, and Trichomonas vaginalis are thought to play a role, although there are conflicting data. Periodontal disease has also been linked to PTD via placental or systemic infections.¹¹ Malaria is also a key player in PTD, low birth weight, and maternal and fetal morbidity and mortality.¹⁴

A genetic association for PTD is reflected in increased incidence among certain families and racial groups. Some women who were born premature have delivered preterm infants, suggesting susceptibility genes. In the United States, non-Hispanic black women are at an increased risk of PTD compared with white women, with one study identifying a susceptibility locus on chromosome 7.¹⁵

Although hard to measure, demographics and lifestyle are found to have a high association with PTD. Women who are at both ends of the spectrum of maternal age (ie, adolescents and those of advanced maternal age) are at higher risk for PTD. Women with low or high body mass index also seem to be at increased risk for PTD, although numerous confounders are associated with weight. Smoking and the abuse of such substances as cocaine and alcohol are also linked to PTD.^16,17

Short interpregnancy intervals (< 6 months) have been linked to PTD, because mothers do not have time to recover from the physical stress and nutritional burden of the pregnancy. This is especially relevant for adolescent girls, who are still growing and competing with the fetus for nutrients. In a meta-analysis of 67 studies of 11 million pregnancies from 62 countries, interpregnancy intervals < 6 months increased the risk of PTD with an odds ratio of 1.4 (95% confidence interval, 1.24–1.58).¹⁸

Chronic diseases such as hypertension, renal insufficiency, and diabetes mellitus are known to be associated with PTD. Moderate to severe anemia in early pregnancy increases the risk of PTD, whereas anemia in the third trimester has no such effect. Anemia is often the result of other diseases such as human immunodeficiency virus (HIV), malaria, poor nutrition, and hemorrhage, all of which are underlying causes of poor maternal and fetal outcomes.

Prevention of PTD

Prevention of PTD is classified as primary (focusing on all women), secondary (focusing on women with a history of preterm birth), and tertiary (focusing on preterm infants).¹⁹ Although data in Western nations reflect the progress in neonatal care with glucocorticoids and advancements in neonatal intensive care units, this is not often the case in low-resource nations. Identifying the risk factors for PTD before conception can prevent future PTD. Because prior PTD is the strongest risk factor for future PTD, eliciting this information in the patient history is important. However, identifying and addressing chronic diseases and behavioral issues (including smoking and substance abuse) before pregnancy is critical. In addition, risk of PTD can be lowered by decreasing the number of high-order multiple gestations by restricting the number of embryo transfers and, when possible, fetal reduction, although there are significant legal, ethical, and religious restrictions to be considered.

During pregnancy, simple diagnosis and treatment of infections such as asymptomatic bacteriuria, sexually transmitted infections, bacterial vaginosis, and periodontal disease can directly reduce the risk of PTD. Cervical cerclages are recommended at 12 to 14 weeks of gestation for women who have had two or more prior second- trimester pregnancy losses or three or more < 34 weeks PTDs.²⁰ More recently, progesterone supplementation (17-alpha-hydroxyprogesterone caproate, 250 mg, intramuscularly weekly from 16–36 weeks) has been found to reduce the risk of PTD in women with a history of PTD and short cervix.²¹ Some studies have reported an increased risk of gestational diabetes with progesterone, ^22,23 whereas others did not.²⁴ Once a woman is in preterm labor, multiple approaches can be used, including bed rest, hydration, tocolytics (calcium channel blockers, beta mimetics, indocin), and magnesium (used also for fetal neuroprotection, it decreases the incidence and severity of cerebral palsy in the baby if delivery is imminent).

Challenges in Low-Resource Settings

In resource-poor settings, data collection regarding PTD is infrequent; when information is collected, definitions are often inconsistent, and live births and still births are not accurately classified. The economic cost of preterm births is extraordinarily high in the United States, with an average first-year medical cost of $32,325 for a preterm infant versus $3325 for a term infant.⁴ This cost is clearly unrealistic in low-resource settings. Neonatal intensive care units are not often available; when they are, the equipment may not be functioning and the staff may not be trained. Often, one sees a room full of empty incubators.

Efforts to Reduce PTD in Low-Resource Settings

Simple and cost-effective efforts have been made to reduce PTD. The data on the effectiveness of preconception care in reducing PTD are limited, but overall, programs that focus on birth spacing, contraception (including prevention of adolescent pregnancies), exercise, optimizing nutrition and prepregnancy weight, micronutrient fortification, screening for and addressing underlying chronic diseases, updating vaccinations, and improving psychological health have been shown to be extremely cost effective.⁴

The incidence of PTD can be reduced by basic antenatal services that screen and treat for sexually transmitted and other infections (eg, HIV, tuberculosis, and malaria), offer dietary support (for malnutrition and obesity), provide vitamin supplementation, teach smoking cessation (and methods of reducing second-hand smoke exposure), identify hypertension and diabetes, and lower the number of multiple gestations and placenta previa. The use of progesterone has not been implemented in most low-resource settings because of the need for cervical length measurement surveillance, and, often, trained staff are lacking.⁴

Although the data on antenatal corticosteroids clearly demonstrate a reduction in neonatal mortality and the incidence of respiratory distress syndrome, the usage in low-resource settings was only 5% to 10%.²⁵ The WHO has antenatal corticosteroids (betamethasone and dexamethasone) on the priority medicine list for reducing infant mortality, and yet they are rarely used.⁴ The use of magnesium sulfate, calcium channel blockers, and beta mimetics is also very low. Increasing the availability and access of these medications, education, and commitment from governments can make significant changes in the outcome of PTD.

Once babies are born, the proven cost-effective intervention known as “kangaroo mother care,” in which premature babies (< 2000 g) are placed in prolonged skin-to-skin contact with their mothers for warmth and frequent breastfeeding, showed a 51% reduction in neonatal mortality in the first week when compared with incubator care.³ Basic neonatal resuscitation with the bag-and-mask or mouth-to-mask have shown to save 80% of neonates.⁴ Other interventions that have been shown to significantly decrease neonatal death include early and exclusive breastfeeding, baby hats, blankets, infection prevention (basic hand washing and clean environment), and, if available, continuous positive airway pressure.

Conclusions

In September 2010, during the United Nations Millennium Develop ment Goals Summit, Secretary-General Ban Ki-moon launched the Every Woman Every Child movement. The goal is to save 16 million women’s and children’s lives by 2015 through financial commitments from governments, nongovernmental organizations, and the private sector to improve health services and delivery to women and children. A transparent method will be used to track the progress of these commitments and the use of proven medications.⁴ It is clear that proven methods to decrease PTD and improve neonatal outcomes are under-used. Focusing on prevention of PTD during the preconception and pregnancy period requires commitment, education, and integration of the health care system. Research focusing on cost-effective solutions, increase in program funding, and commitment from policy makers are some of the necessary steps needed to significantly reduce PTD and neonatal death.

Main Points.

• Worldwide, approximately 15 million babies are born prematurely each year. Prematurity is the leading cause of death among newborns, accounting for 1 million deaths per year, and, after pneumonia, is the second leading cause of death in children under age 5 years.

• Thirty-five countries are currently on track to achieve the fourth Millennium Development Goal of reducing the mortality rate in children under age 5 years by two-thirds between 1990 and 2015.

• Risk factors for preterm delivery (PTD) include (but are not limited to) previous PTD, infection, chronic disease, uterine anomaly, and socioeconomic status, smoking, maternal age, short interpregnancy intervals, and poor nutrition.

• Prevention of PTD is classified as primary (focusing on all women), secondary (focusing on women with a history of preterm birth), and tertiary (focusing on preterm infants).