Disparities in Mortality Rates Among US Infants Born Late Preterm or Early Term, 2003–2005

The purpose of this study was to identify disparities in neonatal, post-neonatal, and overall infant mortality rates among infants born late preterm (34–36 weeks gestation) and early term (37–38 weeks gestation) by race/ethnicity, maternal age, and plurality. In analyses of 2003–2005 data from US period linked birth/infant death datasets, we compared infant mortality rates by race/ethnicity, maternal age, and plurality among infants born late preterm or early term and also determined the leading causes of death among these infants. Among infants born late preterm, infants born to American Indian/Alaskan Native, non-Hispanic black, or teenage mothers had the highest infant mortality rates per 1,000 live births (14.85, 9.90, and 11.88 respectively). Among infants born early term, corresponding mortality rates were 5.69, 4.49, and 4.82, respectively. Among infants born late preterm, singletons had a higher infant mortality rate than twins (8.59 vs. 5.62), whereas among infants born early term, the rate was higher among twins (3.67 vs. 3.15). Congenital malformations and sudden infant death syndrome were the leading causes of death among both late preterm and early term infants. Infant mortality rates among infants born late preterm or early term varied substantially by maternal race/ethnicity, maternal age, and plurality. Information about these disparities may help in the development of clinical practice and prevention strategies targeting infants at highest risk.     

Mortality of twins and singletons by gestational age: a varying-coefficient approach

This study used data from the Swedish Medical Birth Registry between 1982 and 1995 to address the question of whether there is higher mortality in twins in relation to singletons of the same gestational age and to examine the optimal gestational age range for twins. A "varying-coefficient approach" was adopted to estimate the gestational age-specific relative and absolute risks of mortality in twins and singletons, adjusting for size at birth and risk factors of short gestational duration. The models showed that twins born between 29 and 37 weeks of gestation had lower mortality than did singletons of the same gestational age. Twins born at older gestational age had higher mortality than did their singleton counterparts, because longer gestational duration was more advantageous to singletons than to twins. Without adjustment for size at birth, there was an upturn of mortality in twins born after 38 weeks. It is postulated that twins have better health than singletons initially, but they could not enjoy the benefit of a longer gestational duration as much as singletons could. The optimal gestational age for twins appeared to be 37-39 weeks according to neonatal and infant mortality.     

Comparison of infant mortality among twins and singletons: United States 1960 and 1983

Infant mortality among US black and white twins and singletons was compared for 1960 and 1983 using the Linked Birth/Infant Death Data Sets from the National Center for Health Statistics. Both twin and singleton infant mortality rates showed impressive declines since 1960 but almost all of the improvement in survival for both twins and singletons was related to increased birth weight-specific survival rather than improved birth weight distribution. One-half of white twins and two-thirds of black twins weighed less than 2,500 g at birth, and 9% of white twin births and 16% of black twin births were in the very low (less than 1,500g) birth weight category. In 1983, twin infant mortality rates were still four to five times that of singletons. However, twins had a survival advantage in the 1,250-3,000 g range, which persisted after adjustment for gestational age. Cause-specific mortality among twins was considerably higher for every major cause of death: twin mortality risks due to newborn respiratory disease, maternal causes, neonatal hemorrhage, and short gestation/low birth weight were six to 15 times that of singletons. The lowest twin-to-singleton mortality ratios observed were for congenital anomalies and sudden infant death syndrome with relative risks twice that of singletons. The data underscore the need to develop effective strategies to decrease infant mortality among twins.     

Maternal sociodemographic characteristics as risk factors for preterm birth in twins versus singletons

Many studies have examined associations between sociodemographic variables and preterm birth in singletons. However, almost no research has been published on whether variables such as maternal age, race, ethnicity, level of education and smoking are associated with preterm birth among twins in the same way. The purpose of this study was to examine such associations in twins and singletons comparatively. The study population consisted of all 567796 twins and 23297909 singleton births recorded in the US birth records for 1990-95. Gestational age data were rigorously 'cleaned' to solve the problem of biologically implausible birthweight/gestation combinations in vital records. Preterm birth was defined as gestational age < 35 weeks. Some 25.8% of twins and 3.2% of singletons were preterm by this definition. Crude and adjusted relative risks (RR) were estimated using a modified Mantel-Haenszel procedure. We found several characteristics associated with preterm birth in both twins and singletons, e.g. for twins: race (black adjusted RR = 1.30 compared with white non-Hispanic); marital status (unmarried adjusted RR = 1.15 compared with married); and age (< or = 17 years adjusted RR = 1.39 compared with 20-29 years). A similar analysis of singletons revealed stronger associations between the same characteristics and preterm birth, e.g. the adjusted RR for black race was 2.3. These differences in RRs suggest that sociodemographic characteristics have weaker effects on preterm birth among twins than among singletons. Care must be taken in interpreting differences in preterm birth in twins and singletons, as their gestational age distributions differ so markedly.     

Fetal growth and neonatal mortality in Korea

The fetal growth curve and neonatal mortality rate, based on gestational age and birthweight, are important for identifying groups of high-risk neonates and developing appropriate medical services and health-care programmes. The purpose of this study was to develop a national fetal growth curve for neonates in Korea, and examine the Korean national references for fetal growth and death according to their characteristics. Data of Korean vital statistics linked National Infant Mortality Survey conducted on births in 1999 were used in this study. The total livebirths were 621,764 in 1999, which were grouped into singletons (n = 609,643) and twins (n = 9805) for analysis. Birthweight/gestational age-specific fetal growth curves and neonatal mortality rates were based on 250 g of birthweight and weekly gestational age intervals for each characteristic of the birth. The features of high-risk neonates such as small-for-gestational-age and the limit of viability in Korea were different from those of Western countries. Difference in fetal growth and death was also detected in other characteristics of the fetus (gender and plurality of birth) besides race. The fetal growth curve of males was higher than that of females, and was higher in singleton than in twins. The neonatal mortality rate was higher in males (singleton, 2.6; twin, 23.5) than females (singleton, 2.1; twin, 15.9), and higher in twins (19.8/1000) than in singletons (2.4/1000). However, in neonates with gestational age >29 weeks and birthweight >1000 g, the neonatal mortality rate was lower in twins than in singletons. The limit of viability was gestational age 27 weeks and birthweight 1000 g, which was similar in singletons and twins regardless of gender. To improve the health of neonates in a country, it is imperative to investigate the characteristics of fetal growth and death under the particular circumstances of the country. When risk is defined for neonates account must be taken of differences in race, gender and plurality of birth, as the neonatal mortality rate varies depending on those factors.     

Changing patterns of low birthweight and preterm birth in the United States, 1981-98

Low birthweight (LBW) and preterm birth are primary risk factors for infant morbidity and mortality in the US. With increasing multiple births and delayed childbearing, it is important to examine the separate contributions of these characteristics to the increases in LBW and preterm birth rates. US natality records from 1981, 1990 and 1998 were used to calculate LBW (% births <1500, 1500-2499, <2500 g) and preterm (% births <29, 29-32, 33-36, <37 weeks gestation) rates. Data were stratified by maternal race (black or white) and plurality (singleton vs. multiple birth). LBW and preterm rates among singletons were adjusted for maternal age to examine the influence of demographic shifts on LBW trends. From 1981 to 1998, LBW increased 12% among white infants, but remained relatively stable among black infants. During the same time, preterm birth increased 23% among white infants compared with 3% among black infants. For both black and white infants, the increase in LBW and preterm births was greater among multiple births than among singletons. Adjustment for maternal age did not reduce the temporal increase in LBW or preterm birth among singletons. Black infants continue to experience a markedly higher incidence of LBW and preterm birth, but the racial gap in these outcomes has narrowed slightly in recent years as a result of increasing LBW and preterm birth among white births. The differing trends for white and black infants are the consequence of a disparate trend in the incidence and outcome of multiple births coupled with increases in LBW and preterm birth among white singletons. Understanding the differential patterns in birth outcomes among white and black infants is necessary to develop effective interventions designed to decrease racial disparities in pregnancy outcome.     

Size and morbidity in Malawian twins

OBJECTIVE: Twins in developing countries may be disadvantaged due to their small size at birth, compromised nutrition and high infection risk. Although twinning is common in Africa, there are few longitudinal studies of growth and morbidity in this high-risk group. The aim of the present paper was to describe growth and morbidity of Malawian twins compared to singletons. METHODS: Morbidity episodes were recorded at 4 weekly intervals and at extra visits made to health centres for illness. Weight, length, head and arm circumference were recorded at birth and weight, length and MUAC at 4 weekly intervals to 52 weeks of age. RESULTS: Twins showed reduced fetal growth compared to singletons, with increasing fall-off in percentiles from 33 weeks gestation. Infant growth percentiles for twins were below those for singletons at all ages, but showed no fall-off from singleton percentile values. There were no differences in morbidity incidence during infancy between twins and singletons. CONCLUSION: Malawian twins showed no catch-up growth during infancy, their smaller size was not associated with higher morbidity incidence compared to singletons.     

The relationship between maternal birthweight and gestational age in twins and singletons and those of their offspring in Norway

In order to elucidate whether maternal plurality affects offspring intrauterine growth, the relationship between birthweight and gestational age of twins and singletons and those of their first singleton liveborn children in Norway was studied using data from the Medical Birth Registry. The population-based sample consisted of 49 698 mother–offspring pairs (48 842 with singleton and 856 with twin-mothers). In bivariate analyses, no significant differences in mean birthweight and gestational age of offspring of twin and singleton mothers were found, although the mean birthweight and gestational age of the twin-mothers themselves were significantly lower than those of singletons (819 g and 14 days respectively). In multiple regression analysis, the expected birthweight of offspring was 230.3 g (95% CI: 193.2–267.4 g) higher when the mother was a twin than when the mother was a singleton, when controlling for non-standardised maternal birthweight. When adjusting for relative maternal birthweight ( z -score), the association between maternal plurality and offspring birthweight was not statistically significant. The results suggest that being born as a twin has no substantial consequences on offspring growth in utero and show that mean differences in birthweight between twins and singletons should be standardised when both groups are included in multivariate studies.     

Maternal birthweight and outcome of twin pregnancy

There is evidence from singletons that maternal birthweight is positively related to offspring gestational length and birthweight, and some evidence of an inverse relationship with preterm birth. Among twins very preterm birth is the major cause of neonatal mortality and of immediate and later morbidity, including neurodevelopmental impairment. We hypothesised that the relationship between maternal birthweight and gestational length would be more evident in twin than in singleton pregnancies, as there is more variation in gestation in the former. Among 131 singleton mothers carrying twins, there was weak evidence of a positive relationship between maternal birthweight and twin gestational length (+0.6 weeks [95% CI -0.05, +1.3] per kg increase in maternal birthweight, but stronger evidence among 56 of these who went into labour spontaneously (+1.9 weeks [+0.7, +3.1], P = 0.003 for interaction). In the latter group we estimated that the odds of very preterm birth (at <32 weeks) were reduced by 50% [95% CI 10%, 82%] per 250 g increase in maternal birthweight. In the whole cohort, and in this subgroup, maternal birthweight was strongly positively related to both twin offspring total birthweight and total placental weight. Our data, consistent with intergenerational programming of early development, suggest the possibility of a stronger and more clinically relevant association among twins than among singletons. Nevertheless, our sample size was modest and this finding needs to be confirmed in a larger cohort.     

Recurrence of gestational age in sibships: implications for perinatal mortality.

The authors studied the extent to which preterm birth and perinatal mortality are dependent on the gestational ages of previous births within sibships. The study was based on data collected by the Medical Birth Registry of Norway from 1967 to 1995. Newborns were linked to their mothers through Norway's unique personal identification number, yielding 429,554 pairs of mothers and first and second singleton newborns with gestational ages of 22-46 weeks, based on menstrual dates. Siblings' gestational ages were significantly correlated (r = 0.26). The risk of having a preterm second birth was nearly 10 times higher among mothers whose firstborn child had been delivered before 32 weeks' gestation than among mothers whose first child had been born at 40 weeks. However, perinatal mortality in preterm second births was significantly higher among mothers whose first infant had been born at term, compared with mothers whose firstborn child was delivered at 32-37 weeks. Since perinatal mortality among preterm infants is dependent on the gestational age in the mother's previous birth, a common threshold of 37 weeks' gestation for defining preterm birth as a risk factor for perinatal death may not be appropriate for all births to all mothers.     

The undesirable consequences of controlling for birth weight in perinatal epidemiological studies.

OBJECTIVE: To compare the effects of controlling for birth weight with those of controlling for gestational age at delivery in perinatal epidemiological studies using two examples. SETTING: Western Australia. SUBJECTS: Population data: all white births born at 20-46 weeks of gestation in Western Australia during 1985-91 inclusive (n = 147564). Example 1: All Western Australian births from 1980-89 born either at 33-36 weeks inclusive (n = 13607), or born with a birth weight of 2050-2900 g (n = 34107). Example 2: 160 singleton cases of spastic cerebral palsy born to white mothers in Western Australia from 1975-80 and whose gestational age was known, compared with (a) 480 controls individually matched for gender and birth weight and (b) singletons with known gestational age liveborn to white mothers in Western Australia from 1980-81, or 1979-82 if < 30 weeks' gestational age at birth (n = 32031). MEASUREMENTS AND MAIN RESULTS: The risks of cerebral palsy associated with two separate exposures in groups defined by birth weight were compared with those in groups defined by gestational age. The origin of the differences are explained using total population data. The estimates of risk differ when exposure and outcome are both associated with appropriateness of fetal growth. The difference varied with gestational age, being greatest in the moderately preterm (33-36 weeks' gestation). CONCLUSION: Epidemiological studies in which appropriateness of fetal growth is an important variable should be based on gestational age at birth rather than birth weight, whatever the neonatal size or maturity.     

Teen Maternal Age and Very Preterm Birth of Twins

Background: As teen singleton pregnancy is associated with higher risks of adverse birth outcome, and twin pregnancy, regardless of maternal age, may result in poor outcome, teens pregnant with twins may represent a particularly vulnerable group. However, little has been documented regarding teen twin pregnancy outcome. Objective: To characterize the risk of very preterm birth among teens having twins. Design: Cross-sectional analysis of the US 1995–2000 Matched Multiple Birth Data Set. Methods: We calculated the risk of very preterm birth (<33 weeks' gestation) for teen and young adult mothers of twins (≤16 years, 17–18 years, 19–20 years), compared to 21–24 year olds, stratified by race/ethnicity. Adjusted odds ratios were estimated controlling for marital status and entry into prenatal care. Results: Odds of very preterm birth decreased significantly with increasing age. Odds ratios ranged from 2.07 (1.73,2.48) to 1.20 (1.11,1.29) according to maternal age for White teen mothers, from 1.76 (1.48,2.09) to 1.13 (1.03,1.24) for Black teen mothers, and from 2.19 (1.77,2.72) to 1.15 (1.02,1.31) for Hispanic teen mothers. Odds of very preterm birth among teen mothers of twins were about the same as those for teen mothers of singletons. Conclusions: Teens having twins have higher odds of very preterm birth than young adult mothers. However, the association between age and preterm birth was similar among teen mothers having twins as for those having singletons.     

Trends and differentials in higher-birthweight infants at 28–31 weeks of gestation, by race and Hispanic origin, United States, 1990–2002

Birth certificate gestational age data based on the date of the mother's last menstrual period (LMP) are considered problematic. Of particular concern are birthweight distributions for infants reported on the birth certificate as having been delivered at 28–31 weeks' gestation; these distributions have been shown to be distinctly bimodal. The 'second curve' of the birthweight distribution at 28–31 weeks includes implausible birthweight/gestational age combinations and, thus, has been hypothesised to represent erroneous gestational ages due to misidentification of the date of LMP. It has been suggested that such 'misclassification' has declined in recent years and that this change can affect trends in preterm birth rates (<37 weeks' gestation), particularly rates among non-Hispanic black infants. This present study used primarily simple and multivariable analyses to review trends and differentials in birthweight distributions at 28–31 weeks by race and Hispanic origin of the mother. It aggregated data for the years 1990–92 and 2000–02 from the US vital statistics Natality files.
Over the decade, the percentage of births in the second curve declined for all births and for each racial and Hispanic origin group studied. The largest decline was observed for non-Hispanic blacks; the smallest for Hispanic births. Later initiation of prenatal care, younger maternal age, lower educational attainment, higher birth order and vaginal and singleton delivery were positively associated with a larger second curve, suggesting misclassification of gestational age. Declines in the second curve over the study period were suggested to contribute significantly to the observed decrease in overall preterm birth rates for non-Hispanic black births. Further analysis is needed to estimate the influence of reporting error on preterm birth rates by race and Hispanic origin.     

Racial differences in birthweight for gestational age and infant mortality in extremely-low-risk US populations

Using national data, we develop and contrast the birth-weight percentiles for gestational age by infants of extremely-low-risk (ELR) White and African-American women and examine racial differences in the proportion of small-for-gestational-age (SGA) births. We then scrutinise racial variations in infant mortality rates of the infants of ELR women. We further compare the infant mortality rates of infants at or below the 10th percentile of birthweight for gestational age of each race group to determine whether infants with similar restricted fetal growth have comparable risks of subsequent mortality. Single live births, 34-42 weeks' gestation, to White and African-American US-resident mothers were selected from the 1990-91 US Linked Live Birth--Infant Death File (n = 4,360,829). Extremely-low-risk mothers were defined as: married, aged 20-34 years, 13+ years of education, multiparae, with average parity for age, adequate prenatal care, vaginal delivery, and no reports of medical risk factors, tobacco use or alcohol use during pregnancy. Marked racial variation in birthweight percentiles by gestational age was evident. Compared with ELR White mothers, the risk of an SGA infant was 2.64 times greater for ELR African-American mothers and the risk of infant mortality was 1.61 times greater. For the ELR group, the infant mortality rates of African-American and White infants at or below the 10th percentile of birthweight for gestational age of their respective maternal race group were essentially identical after controlling for gestational age. In conclusion, race differences in fetal growth patterns remained after controlling for risk status. Efforts to remove racial disparities in infant mortality will need to develop aetiological pathways that can explain why African-Americans have relatively higher rates of preterm birth and higher infant mortality rates among term and non-SGA infants.     

A comparison of recent trends in infant mortality among twins and singletons

Overall infant mortality rates have steadily declined in recent years. The goal of this study was to examine whether recent declines in infant mortality were similar for twins and singletons, and to assess the impact of differing birthweight distributions on these relationships. Linked birth and infant death records for 1985-86 and 1995-96 were used to calculate infant mortality rates for twins and singletons for the two time periods. Bootstrap simulations were used to estimate rates of decrease between the two time periods and to determine whether these rates differed between twins and singletons. Between 1985-86 and 1995-96, infant mortality among twins declined significantly faster than among singletons (36% vs. 29%, P < 0.05). This difference was true for both black and white infants (black: 28% for twins vs. 22% for singletons; white: 38% for twins vs. 31% for singletons). Within birthweight categories, infant mortality declined more rapidly among twins than among singletons, although differences were not always significant. Factors and circumstances that contributed to the infant mortality decline in the United States have benefited twins to a greater extent than singletons.     

Lower mortality but higher neonatal morbidity over a decade in very preterm infants

Better perinatal care has led to better survival of very preterm children, but may or may not have increased the number of children with cerebral and pulmonary morbidity. We therefore investigated the relationship between changes in perinatal care during one decade, and short-term outcome in very preterm infants. Perinatal risk factors and their effects on 28-day and in-hospital mortality, and on intraventricular haemorrhage and bronchopulmonary dysplasia (BPD) in survivors, were compared in two surveys of very preterm singleton infants in the Netherlands. Between 1983 and 1993, 28-day mortality decreased from 52.1% to 31.8% in infants of 25-27 weeks' gestation and from 15.2% to 11.3% in infants of 28-31 weeks' gestation. The incidence of intraventricular haemorrhage in survivors did not change (44.4% and 43.3% in infants of 25-27 weeks' gestation, and 29.0% and 24.0% in infants of 28-31 weeks' gestation). The incidence of BPD in survivors increased from 40.3% to 60.0% in infants of 25-27 weeks' gestation and remained similar in infants of 28-31 weeks' gestation (8.5% and 9.8% respectively). In multivariable analysis, higher mortality was associated with congenital malformation, low gestational age, low birthweight, no administration of steroids before birth, low Apgar scores and intraventricular haemorrhage, in 1983 as well in 1993, and with male gender in 1993. The effect of maternal age on mortality diminished significantly between 1983 and 1993. Intraventricular haemorrhage in surviving children was associated with low gestational age and artificial ventilation, both in 1983 and in 1993. The effect of artificial ventilation on the incidence of intraventricular haemorrhage diminished significantly between 1983 and 1993. BPD was associated with low gestational age and artificial ventilation, both in 1983 and in 1993, and with low birthweight and caesarean section in 1993. We conclude that the better survival of very preterm infants, especially of those of 25-27 weeks' gestation, has been accompanied by a similar incidence (and thus with an increased absolute number) of children with intraventricular haemorrhage and by an increased incidence of children with BPD.     

Consanguinity: a risk factor for preterm birth at less than 33 weeks' gestation

Consanguinity promotes homozygosity of recessive susceptibility gene variants and can be used to investigate a recessive component in diseases whose inheritance is uncertain. The objective of this study was to assess the association between consanguinity and preterm birth (PTB), stratified by gestational age and clinical presentation (spontaneous vs. medically indicated). Data were collected on 39,745 singleton livebirths without major birth defects, admitted to 19 hospitals in Lebanon, from September 2003 to December 2007. Deliveries before completed 33 weeks' gestation and deliveries at 33-36 weeks' gestation were compared, with respect to cousin marriage, with those after completed 36 weeks' gestation by using multinomial multiple logistic regression. Overall, infants of consanguineous parents had a statistically significant 1.6-fold net increased risk of being born at less than 33 weeks' gestation compared with infants of unrelated parents. This association was statistically significant only with spontaneous PTB. There was no increased risk of being born at 33-36 weeks' gestation associated with consanguinity for both clinical presentations of PTB. Our findings support a genetic contribution to early onset PTB and suggest that early PTB should be targeted in future genetic studies rather than the classic lumping of all births less than 37 weeks' gestation.     

Assisted reproductive technologies and birth outcomes: overview of recent systematic reviews

Several systematic reviews have been published recently on birth outcomes of infants conceived through assisted reproductive technologies (ART), compared with infants conceived spontaneously. These outcomes include perinatal mortality, preterm birth, low birthweight and birth defects. Methodological limitations of many of the individual studies (including small sample size, potential for bias in ascertainment of outcomes and considering singletons and multiples together) were obviated in these reviews by excluding studies where methods were considered inadequate, by conducting meta-analyses using data from all methodologically sound studies (small and large) and by examining singletons separately. Overall, the reviews indicate few differences between outcomes in ART twins compared with twins conceived spontaneously. However, in singleton ART infants, there are around two-fold increases in risk of perinatal mortality, low birthweight and preterm birth, about a 50% increase in small for gestational age and a 30-35% increase in birth defects, compared with singletons conceived spontaneously. Couples considering ART should be counselled about the increased risk of adverse outcomes. Epidemiologists, in conjunction with clinical and laboratory colleagues, should now focus on large, methodologically sound studies with long-term follow up that seek to identify the reasons for these increased risks and their long-term consequences, whether they are associated with particular technologies and causes of infertility, and how they might be reduced.     

Maternal smoking and adverse birth outcomes among singletons and twins

OBJECTIVES: This study assessed the effects of maternal smoking on birth outcomes among singletons and twins. METHODS: An algorithm was developed to link twins with their siblings in the 1995 Perinatal Mortality Data Set. A random-effects logistic regression model was then used to estimate the association between maternal smoking and several adverse outcomes for a random sample of singletons and for all twins with available maternal smoking information. RESULTS: The algorithm successfully linked sibling pairs for 91% of the twin sample. Maternal smoking was associated with a significantly increased risk of low birthweight, very low birthweight, and gestation of less than 33 weeks for both singletons and twins and with an increased risk of gestation of less than 38 weeks, infant mortality, and placental abruption for singletons. Among smokers, negative impacts on the risk of low birthweight, very low birthweight, and extreme premature delivery were significantly higher for women carrying twins. CONCLUSIONS: Some of the negative effects of smoking on low birthweight and preterm delivery are greater for twins than for singletons. Women carrying twins should be warned that smoking increases their already high risk of serious infant health problems.