CHDD researcher looks beyond prenatal period in search for causes of poor pregnancy outcomes

Babies who weigh less than 2,500 grams (about 5.5 pounds) at birth require more care and are at increased risk for developmental problems. Additional health services required by low birth weight infants are estimated to cost nearly $4 billion per year.

Efforts to prevent low birth weight have emphasized prenatal care. These efforts have been largely unsuccessful because they neglect the host of complex factors that play a role in birth outcomes and are present long before conception, according to CHDD research affiliate Dr. Irvin Emanuel.

Although prenatal care is important, it is not a cure-all, argues Emanuel, professor of epidemiology and pediatrics, and former director of CHDD. "Improvement in pregnancy outcomes is a long-term process," he says. "There is no panacea, no way of solving it immediately."

Increasingly, evidence uncovered by Emanuel and other researchers who study birth outcomes in populations points to the significance of nongenetic factors that are passed from one generation to the next. These intergenerational factors encompass the conditions under which a child is born and grows up. They are closely tied to socio-economic status and their effect is measured by quality of growth.

"Good growth means good health and good health means good growth," stresses Emanuel. "Poor kids don't grow as well as kids from families who are well off."

Intergenerational factors can interfere with the genetically controlled aspect of growth, preventing full genetic expression. In an individual ­a mother-to-be­the intergenerational effect shows up in her own pre- and post-natal growth. In a population, the intergenerational effect is evident in the trend of increasing adult stature in affluent populations. The opposite trend appears in economically declining populations, which have been shown to undergo a decrease in adult stature. Although the reasons are not understood, it has long been known that tall mothers have better birth outcomes, Emanuel points out.

Emanuel has been studying intergenerational factors and pregnancy outcomes for more than 20 years. Over that time the epidemiological investigations he has undertaken have shown a relationship between maternal growth and such pregnancy outcomes as low birth weight, prematurity, intrauterine growth retardation, and infant death.

Emanuel and his colleagues conducted one of the first studies to investigate the relationship between maternal birth weight and pregnancy outcome. The cohort they studied consisted of 748 white women who delivered babies during a two-year period from 1977 to 1979, and were born in Washington state after 1948, when the recording of birth weight on birth certificates began. The researchers found that a mother's weight at her own birth was related to the risk for low birth weight in her offspring as well as the risk for preterm birth, the baby's need of neonatal intensive care, and respiratory distress syndrome in the infant.

In subsequent work using data on singleton births from the 1958 national cohort of British births collected for the British National Child Development Study, Emanuel found evidence of the intergenerational effect passing through the mother's line and extending through at least three generations. He and his colleagues examined a variety of associations between characteristics of parents and grandparents and baby's birth weight. Even after adjusting for such important factors in birth weight as maternal birth weight, smoking during pregnancy, and baby's sex and birth order, he found a significant relationship between the baby's birth weight and the maternal grandmother's height. The grandmother's height was used as a measure of growth because the data didn't extend far enough back in time to include the grandmother's birth weight. In general, the taller the grandmother, the more the baby weighed at birth.

The study also revealed a significant relationship between the baby's birth weight and maternal grandfather's social class, as determined by occupation. Having a grandfather in a blue-collar versus a white-collar occupation reduced the baby's birth weight by an average of 95 grams.

When Emanuel looked at twin birth data from the same cohort, he discovered a paradox that provided a clue as to how the intergenerational effect might work. Although the female twins in the cohort were of lower birth weight than the singletons, they went on to have bigger babies. This seeming contradiction suggested that certain times during intrauterine growth, specifically the early portions of pregnancy, are significant in long-term reproductive effects. In twin gestation, growth in the first two trimesters follows a pattern similar to singleton gestations, but diverges in the last trimester, when there is a high rate of increase in fetal body mass. The growth of twins is retarded only in the last trimester, so they gain less body mass. Birth defects and congenital malformations are known to be related to disruptions during critical periods in development. A small number of autopsy studies of low birth weight infants who died perinatally have shown that these infants' organs, except for the brain, were small. Small organs could be attributed to a reduced number of cells in the organs, a reduced amount of cytoplasm in the cells, or perhaps a combination of both, explains Emanuel.

"In effect, we're looking at a sort of microscopic birth defect," Emanuel says. "Although the organs of living children haven't been thoroughly studied, it appears that tiny infants have small organs. We know that small infants remain small as they grow. There are permanent physiological consequences of being abnormally small at birth."

A number of questions about intergenerational factors and birth outcomes remain. A big question is the cause of the excess number of low birth weight and preterm births in African Americans as compared with whites and other racial/ethnic groups. In a new study, funded by the federal Maternal and Child Health Bureau, Emanuel and his colleagues are using data from several existing statewide databases in Washington state to examine the maternal birth weight and reproductive outcomes for pregnancies in the state during an eight-year period. Most studies of intergenerational factors have been conducted in white populations. By encompassing a large number of pregnancies, the researchers will be able to look at relationships among reproductive outcomes and parental characteristics in African Americans, Native Americans and Hispanics, as well as whites.

"Understanding how a mother's birth weight mediates her reproductive outcomes can lead to interventions designed to decrease the risk of poor birth outcomes," says Emanuel. "In the meantime, we need to nurture children better so that they will grow better postnatally. Too many of our infants are biologically healthy and capable of normal growth, but grow up in suboptimal environmental circumstances that impair their growth, so the issues just repeat themselves from one generation to the next."

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