Kwang-sun Lee

Neonatal mortality: an analysis of the recent improvement in the United States.

To test the hypothesis that the recent substantial decline in the United States neonatal mortality rate (20.0/1000 in 1950 to 11.6/1000 in 1975) is associated with improvements in perinatal medical care, we examined this change in relation to the two primary components which determine neonatal mortality: birthweight distribution and birthweight-specific mortality. No improvement in the weight distribution of U.S. live births has occurred during this 25-year period, indicating that the change in neonatal mortality is attributable to improved survival for one or more birthweight groups. Decline in the mortality rate in the first 15 years was slow; three-fourths of the decline in the entire 25-year period occurred since 1965. With the exception of perinatal medical care, factors known to affect survival at a given birthweight have not changed in prevalence in the 25-year period. It is a plausible hypothesis that improved perinatal medical care is a major factor in declining neonatal mortality in the U.S.

Infant mortality from congenital malformations in the United States, 1970-1997.

OBJECTIVE We examined a trend in infant mortality caused by congenital malformations in the United States, particularly for the racial disparity between whites and nonwhites. METHODS We used US annual summary data on cause‐specific infant mortality for 1970–97 and detailed birth and infant death linked data for 1985–87, 1989–91, and 1995–97. RESULTS Congenital malformations became a more prominent cause of infant mortality in 1997 and accounted for 22.1% of all infant deaths compared with 15.1% in 1970. Congenital malformations of nervous, cardiovascular, and respiratory systems accounted for more than 60% of all malformation deaths. Malformations incompatible with life (anencephaly, encephalocele, hypoplastic lungs, renal agenesis, and trisomies 13 and 18) were the cause of one‐third of all malformation deaths. In 1970–71, infant mortality caused by congenital malformations in nonwhites was lower, 2.6 (confidence interval [CI] 2.5, 2.7) per 1000, compared with whites, 3.1 (CI 3.0, 3.1) per 1000. However, in 1996–97, the rate of congenital malformation‐specific infant mortality was higher in nonwhites, 1.7 (CI 1.7, 1.8) per 1000, compared with whites, 1.6 (CI 1.5, 1.6) per 1000. This trend was most pronounced with central nervous system malformations. Although whites had an almost two‐fold higher infant mortality rate from central nervous system malformations compared with nonwhites in 1970–71, this disparity was no longer present by 1996–97. CONCLUSION Congenital malformations have become a leading cause of infant mortality in the 1990s. Over the last several decades, this mortality declined more slowly in nonwhites than in whites.

Maternal age and incidence of low birth weight at term: A population study

A total of 184,567 singleton live births with gestational ages of 40 weeks were examined from the 1980-1984 Illinois birth certificate data to determine the independent effect of maternal age on the incidence of low birth weight at term. The incidence is highest in mothers less than 17 years of age (3.2%) and gradually declines with advancing maternal age to reach 1.3% in women aged 25 to 34 years. It increases to 1.7% for those greater than 35 years of age. To separate out the independent effect of maternal age on the incidence of low birth weight infants at term, the presence of other maternal factors, such as race, education, parity, marital status, and prenatal care, were adjusted by use of a series of multiple logistic regression analyses. All of these analyses consistently demonstrated that the adjusted risk for low birth weight at term is the lowest in teenagers and increases with advancing maternal age. These results indicate that the high incidence of this factor in young mothers apparently reflects their poor sociodemographic and prenatal care status. Advancing maternal age is associated with a decreased potential for fetal growth, possibly reflecting biologic aging of maternal tissues and systems or the cumulative effects of disease.

The very low-birth-weight rate: Principal predictor of neonatal mortality in industrialized populations

We have examined the relationship between the rate of very low-birth-weight deliveries in a population and the neonatal mortality of that population on three ecologic levels: in one hospital over a 12-year span; among the 50 states and the District of Columbia; and among 13 industrialized nations. In each of the three sets of populations the VLBW rate is an excellent predictor of neonatal mortality, accounting for about three-quarters of the variance in the outcome in all of the populations studied. The relatively high neonatal mortality of the United States as compared to that in some other industrialized nations is primarily attributable to its disadvantageous birth-weight distribution. Holding the adverse birth-weight distribution constant, the United States appears to do better than most of these nations in neonatal mortality. The weight distribution of live births in any population is closely linked to indices of social class. Survival of infants at a given birth weight, however, might well be a function of perinatal care. Since weight-specific mortality rates for populations are not widely available, examination of the variance in neonatal mortality rates once the VLBW rate is held constant might be a first step in comparing the quality of medical care for newborn infants among different populations.

Relationship of cesarean delivery to lower birth weight-specific neonatal mortality in singleton breech infants in the United States.

OBJECTIVE The preferred route of delivery for breech presentation has been controversial. We compared the birth weight-specific neonatal mortality of vaginal births to cesarean births in singleton births with breech presentation. METHODS A total of 371,692 singleton live births with breech presentation were selected for the study from the United States birth cohorts for the years 1989-1991. Differences in birth weight specific mortality were compared using a z-statistic for differences in proportions and by logistic regression. RESULTS Compared to primary vaginal births, primary cesarean births had significantly lower neonatal mortality for all birth weight groups, despite increased prevalence of fetal malformations in the cesarean as compared with vaginally delivered group. This mortality difference was greatest in the first hour of life. Difference in overall neonatal (less than 28 days) mortality rate ranged from a low of 1.6-fold in the 500-749 g group (726.6 per 1000 vaginal births compared with 456.3 per 1000 cesarean births, P < .001) to as high as about three-fold in the 1250-1499 g group (232.9 per 1000 vaginal births compared to 72.5 per 1000 cesarean births, P < .001). In the group with birth weights over 2500 g, neonatal mortality in the primary vaginal births was 5.3 per 1000 and in the primary cesarean births, 3.2 per 1000 (P < .001). Similarly, repeat cesarean births had significantly lower birth weight-specific neonatal mortality, compared with vaginal births after previous cesarean. CONCLUSION Singleton live births with breech presentation delivered by cesarean had lower birth weight-specific neonatal mortality as compared with vaginal births.

If tocolytic magnesium sulfate is associated with excess total pediatric mortality, what is its impact?

The Magnesium and Neurologic Endpoints Trial was a randomized controlled trial (RCT) done to learn whether or not receiving magnesium sulfate during preterm labor could prevent cerebral palsy. Unexpectedly, in the tocolytic arms of the trial, seven (including one set of twins) of 46 cases assigned to receive magnesium ended in total pediatric mortality (fetal + neonatal + postneonatal), compared to none of 47 cases assigned to other tocolytics ending in death. The difference between the two treatment arms is highly statistically significant (risk difference 15.2%; 95% confidence interval 4.8, 25.6; P = .006). If this relationship is confirmed by experimentation with animals or through the conduct of a large RCT at other institutions, it is possible that tocolytic magnesium will be found to be associated with the deaths of several thousand newborns in the United States annually. If the true excess total pediatric mortality is 10%, and if magnesium accounts for 40% of all tocolytics used, then tocolytic magnesium increases the absolute number of infant deaths by about 4800 every year.

Perinatal death and tocolytic magnesium sulfate

Objective To determine whether there is a significant association between perinatal mortality and exposure en route for total doses of tocolytic magnesium sulfate larger than 48 g. Methods We did a case-control study in which cases were defined as neonates or fetuses who died after being exposed to tocolytic magnesium sulfate and controls were those who survived exposure. The study included fetuses and neonates who weighed between 700 and 1249 g and whose mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital between January 1, 1986, and March 31, 1999. We excluded women who received prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on chronic hypertension, and fetuses or neonates with major congenital anomalies. Data were analyzed by Fisher exact test, χ2 test, Student t test, Mann–Whitney U test, multivariable logistic regression, and Cochrane–Armitage trend test. Results Controlling for birth weight or gestational age, year of delivery, receipt of betamethasone, acute maternal disease, and maternal race in a multivariable model, we found that exposure to total doses of tocolytic magnesium sulfate exceeding 48 g was significantly associated with increased perinatal mortality (adjusted odds ratio 4.7; 95% confidence interval 1.1, 20.0; P = .035). Using the Cochrane–Armitage trend test, we found that a significant dose response was present (P = .03), but one that was most consistent with a threshold effect. Conclusion Our findings support the hypothesis that high doses of tocolytic magnesium sulfate are associated with increased perinatal mortality among fetuses and neonates weighing 700–1249 g.

Trend in mortality from respiratory distress syndrome in the United States, 1970-1995☆☆☆

OBJECTIVE We examined the trend in mortality caused by respiratory distress syndrome (RDS) and its impact on changes in infant and neonatal mortality rates (IMR, NMR) in the United States. STUDY DESIGN Data on infant deaths in the United States for the period 1970 through 1995 were used to compare RDS-specific IMR to other cause-specific IMR. Data from the U.S. birth cohorts of 1985 through 1991 were used to examine birth weight- and RDS-specific NMRs. RESULTS IMR from RDS declined from 2.6 per 1000 live births in 1970 to 0.4 per 1000 in 1995. More than three quarters of this decline occurred between 1970 and 1985. RDS-specific NMR declined by 13% between 1985 and 1988 and by more than twofold greater, that is, 28%, between 1988 and 1991. There was also a significant reduction in postneonatal mortality from chronic lung diseases between 1988 and 1991. CONCLUSIONS Most of the reduction in mortality from RDS occurred before the introduction of surfactant therapy. The recent accelerated reduction in mortality from RDS between 1988 and 1991 was temporally associated with widespread use of surfactant therapy and was the single most important factor for reduction in overall NMR in the United States.

A survey of the newborn populations in Belgium, Germany, Poland, Czech Republic, Hungary, Bulgaria, Spain, Turkey, and Japan for the G985 variant allele with haplotype analysis at the medium chain Acyl-CoA dehydrogenase gene locus: Clinical and evolutionary consideration

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of fatty acid metabolism. It is one of the most frequent genetic metabolic disorders among Caucasian children. The G985 allele represented 90% of all the variant alleles of the MCAD gene in an extensive series of retrospective studies. To study the distribution of the G985 allele, newborn blood samples from the following countries were tested; 3000 from Germany (1/116). 1000 each from Belgium (1/77). Poland (1/98), Czech Republic (1/240). Hungary (1/168), Bulgaria (1/91), Spain (1/141). Turkey (1/216), and 500 from Japan (none). The frequency is shown in parentheses. The haplotype of G985 alleles in 1 homozygote and 57 heterozygote samples were then analyzed using two intragenic MCAD gene polymorphisms (Iaq1 and GT-repeat). The result indicated that only 1 of the 10 known haplotypes was associated with the G985 mutation, suggesting that G985 was derived originally from a single ancestral source. We made a compilation of the G985 frequencies in these countries and those in nine other European countries studied previously. The G985 distribution was high in the area stretching from Russia to Bulgaria in the east and in all northern countries in western and middle Europe, but low in the southern part of western and middle Europe. The incidence among ethnic Basques appeared to be low. This distribution pattern and the fact that all G985 alleles belong to a single haplotype suggest that G985 mutation occurred later than the delta F508 mutation of the CFTR, possibly in the neolithic or in a later period, and was brought into Europe by IndoEuropean-speaking people. The panEuropean distribution of the G985 allele, including Slavic countries from which patients with MCAD deficiency have rarely been detected, indicates the importance of raising the level of awareness of this disease.

Risk of Low Birth Weight Associated with Advanced Maternal Age Among Four Ethnic Groups in the United States

Objectives: To examine and compare the risk of low birth weight associated with delayed childbearing in four ethnic groups using nationally representative data in the United States. Methods: We compared the risk of low (<2.5 kg) birth weight among African Americans, Mexican Americans, Puerto Ricans, and non-Hispanic whites using birth data for the United States obtained from the National Center for Health Statistics. Comparisons were done separately for first births and births of second or higher order and in terms of odds ratios, risk differences and attributable fractions of very low (<1.5 kg), middle low (1.5–2.5) and overall low birth weight. Statistical analysis included use of logistic regression models with likelihood ratio tests for interaction effects. Results: African Americans and Puerto Ricans, and to a lesser extent Mexican Americans, had higher risk differences associated with advanced maternal age. For first births, the risk differences associated with advanced maternal age (≥35 years) in low birth weight were 5.3% (95% CI, 4.7–6.0), 4.3% (95% CI, 1.7–6.9), and 3.7% (95% CI, 2.8–4.5) for African Americans, Puerto Ricans, and Mexican Americans, respectively, as compared with 2.6% (95% CI, 2.4–2.7) for non-Hispanic whites. On the other hand, the odds ratios associated with advanced maternal age were more similar across the four ethnic groups. Differences were greater for all ethnic groups in the case of first births as compared with births of second or higher order. Conclusions: Advanced maternal age appears to be associated with for the most part similarly increased odds of low birth weight for African Americans, Mexican Americans, Puerto Ricans, and non-Hispanic whites. However, the age-related increments in the risk of low birth associated with advanced maternal age are greater for African Americans, Puerto Ricans and, to a lesser extent, Mexican Americans, as compared with non-Hispanic whites.