Indicators of fetal growth and infectious disease in childhood--a birth cohort with hospitalization as outcome

We evaluated the association between indicators of fetal growth and hospitalization with infectious disease during childhood in a cohort of 10,400 newborns. The cohort was based on children born to mothers who at about 36 weeks of gestation attended the midwife centres in Odense and Aalborg, Denmark for a routine examination. Women were recruited to the study from April 1984 to April 1987. After linkage with the National Hospital Registry, the first hospitalization with infectious disease from 6 months up to 12 years of age was identified. The cumulative incidence of hospitalization with infectious disease during follow-up was 18.9%. Preterm birth was associated with an increased risk of being hospitalized with infections during childhood (incidence rate ratio: 1.67,95% CI: 1.33–2.10); low birth weight had a similar association, but only in preterm birth. Reduced birth length related to the head was correlated with an increased risk of hospitalization with infections. The effect of gestational age was mainly seen in the period close to the time of birth, but the children who were short at birth appeared to remain at increased risk throughout the age interval under analysis. In conclusion, the study suggests that preterm birth was the main factor underlying the association between low birth weight and the increased risk of hospitalization with infectious disease during childhood. However, it could not explain the increased risk in children who were short at birth.     

Previous Adverse Outcome of Term Pregnancy and Risk of Preterm Birth in Subsequent Pregnancy

Objective Evaluate risk of preterm birth (PTB, < 37 completed weeks’ gestation) among a population of women in their second pregnancy with previous full term birth but other adverse pregnancy outcome. Methods The sample included singleton live born infants between 2007 and 2012 in a birth cohort file maintained by the California Office of Statewide Health Planning and Development. The sample was restricted to women with two pregnancies resulting in live born infants and first birth between 39 and 42 weeks’ gestation. Logistic regression was used to calculate the risk of PTB in the second birth for women with previous adverse pregnancy outcome including: small for gestational age (SGA) infant, preeclampsia, placental abruption, or neonatal death (≤ 28 days). Risks were adjusted for maternal factors recorded for second birth. Results The sample included 133,622 women. Of the women with any previous adverse outcome, 4.7% had a PTB while just 3.0% of the women without a previous adverse outcome delivered early (relative risk adjusted for maternal factors known at delivery 1.4, 95% CI 1.3–1.5). History of an SGA infant, placental abruption, or neonatal death increased the adjusted risk of PTB in their second birth by 1.5–3.7-fold. History of preeclampsia did not elevate the risk of a preterm birth in the subsequent birth. Conclusions for Practice The findings indicate that women with previous SGA infant, placental abruption, or neonatal death, despite a term delivery, may be at increased risk of PTB in the subsequent birth. These women may be appropriate participates for future interventions aimed at reduction in PTB.

     

Obstructive pulmonary disease in old age among individuals born preterm

There are only few studies of the association between preterm birth and risk of chronic lung disease in old age. The aim of this study was to assess the association between poor fetal growth, preterm birth, sex and risk of asthma and Chronic Obstructive Pulmonary Disease (COPD) in adulthood. We have followed up a cohort of all infants born preterm (<35 weeks) or with low birth weight (<2,000 and <2,100 g for girls and boys, respectively) and an equal number of controls in a source population of 250,000 individuals born from 1925 through 1949 in Sweden (6,425 subjects in total). Cases of asthma and COPD were identified through the Swedish Patient Register and we considered cohort subjects as cases if they had a main or additional discharge diagnosis of asthma or COPD. For any obstructive airways disease, there was a statistically significant increase in risk with decreasing birth weight and gestational duration among women but not among men. Compared to women born at term, women born before 32 weeks of gestation had a hazard ratio for any obstructive airways disease and asthma of 2.77 (95 % CI 1.39–5.54) and 5.67 (1.73–18.6), respectively. Low birth weight and preterm birth are risk factors for obstructive airways disease also among the old, but the importance of these risk factors differs between the sexes.     

The impact of birth weight on infectious disease hospitalization in childhood

Low birth weight, a result of preterm birth or intrauterine growth restriction, is a well-established indicator of survival in childhood. However, corresponding epidemiologic studies of the association between low birth weight and morbidity from infections throughout childhood are sparse. The authors evaluated the relation between birth weight and infectious diseases throughout childhood in a population-based cohort study comprising all children born in Denmark from 1977 through 2004 (n = 1.7 million). Information on birth weight, gestational age, and potential confounding variables was linked to the children in the cohort, together with information on hospitalization with infectious disease. Poisson regression yielded rate ratios of hospitalization according to birth weight. The authors found that birth weight was inversely associated with risk of infectious disease hospitalization; among children aged 0-14 years, the risk of hospitalization increased 9% for each 500-g reduction in birth weight (increase in rate ratio = 1.09, 95% confidence interval: 1.09, 1.11). The effect was found to peak in infancy and to persist until 10 years of age. It was present also in children born at term (37-41 weeks of gestation). The present study is the first to demonstrate the measurable impact of birth weight on infectious diseases throughout childhood.     

Emergency department utilization during the first year of life among infants born to women at risk of disability

BackgroundWomen with disabilities are at risk for poor birth outcomes. Little is known about longer-term health and healthcare utilization of infants of women with disabilities.ObjectivesWe identified women at risk for disability and evaluated their infants’ emergency department (ED) utilization during the first year of life.Study designThis population-based cohort study used Massachusetts 2007–2009 birth certificates linked to 2007–2010 hospital discharge data. Access Risk Classification System categorized ICD-9 CM/CPT codes into disability risk categories. Infant ED visits were evaluated overall and by severity (emergent/intermediate vs. non-emergent). Cox proportional hazards models provided adjusted estimates. Results were stratified by gestational age (preterm, < 37 weeks, term, 37 + weeks).ResultsOf 218,599 women, 6.7% were at risk of disability. Infants born to women at risk had a higher rate of ED visits in their first year than infants born to women not at risk: 0.85 visits/person-year (95% CI 0.84–0.87) vs. 0.55 (0.55–0.55) for term, 0.74 (0.70–0.77) vs. 0.55 (0.54–0.56) for preterm. Utilization varied by maternal diagnosis. Emergent/intermediate and non-emergent visits were both elevated among infants born to women at risk for disability. In adjusted analyses, term infants of women with musculoskeletal diagnoses (HR = 1.3, 95% CI 1.2–1.4) and preterm infants of women with circulatory diagnoses (HR = 1.2, 1.0–1.3) had the highest hazards of ED visit vs. infants of women not at risk of disability.ConclusionMaternal disability risk is associated with postnatal infant ED utilization; utilization varies by maternal diagnosis. Interventions to improve health of infants born to women with disabilities are warranted.     

Cerebrovascular and ischemic heart disease in young adults born preterm: a population-based Swedish cohort study

Preterm birth is associated with overall cardiovascular mortality in young adulthood, but which specific conditions that underlie this association is unknown. We studied mortality and morbidity from cerebrovascular and ischemic heart disease in individuals born preterm. In a nationwide Swedish study, we included 1,306,943 individuals without congenital malformations born between 1983 and 1995, followed from 15 years of age to December 31st, 2010. Of these, 73,489 (5.6 %) were born preterm (<37 weeks of gestation). Cox proportional hazards regression analysis was used to calculate hazard ratios (HR) with 95 % confidence intervals (CI), after adjusting for maternal characteristics and birth weight for gestational age. Of 955 incident cases of cerebrovascular disease, 58 (6.1 %) occurred in preterm born subjects. The corresponding numbers of ischemic heart disease cases were 180 and 13 (7.2 %), respectively. Birth before 32 weeks was associated with a nearly twofold increased risk of cerebrovascular disease; adjusted HR, (95 % CI) = 1.89 (1.01–3.54) compared to term born individuals, whereas individuals born at 32–36 weeks were not at increased risk. Preterm birth was not associated with later ischemic heart disease; no cases of ischemic heart disease were recorded among those born before 32 weeks and the HR (95 % CI) for those born at 32–36 weeks of gestation was 1.45 (0.81–2.57), compared to term-born individuals. Birth before 32 weeks is associated with increased risk of cerebrovascular disease in young adulthood. Our data suggest that cardiovascular health promotion in follow-up programs after very preterm birth may be beneficial.     

Socioeconomic inequality in birth weight and gestational age in Denmark 1996–2007: Using a family-based approach to explore alternative explanations

A large body of literature has reported associations between socioeconomic position and adverse pregnancy outcomes even in affluent egalitarian welfare states. This study explored the nature of this relationship by examining women who changed socioeconomic position between pregnancies and women who were siblings but were different in terms of socioeconomic position. Data consisted of 471,215 live born singletons born in Denmark 1997–2007 with at least one sibling or one first cousin. We examined parental educational attainment and household income in relation to preterm birth and small for gestational age using Cox regression. Household income was only weakly related to these outcomes. Paternal education was strongly associated with the outcomes only in the cohort analyses. Maternal education was inversely associated with preterm birth only in the cohort analyses, where the least educated women had the highest risk. Maternal education was inversely associated with the risk of small for gestational age in cohort analyses, attenuated between mothers who were siblings, and not present between children who were siblings. For example, the hazard ratio of preterm birth of women with a college/university degree when compared to women with only mandatory education was 0.64 (95% confidence interval: 0.60–0.67) in the cohort analysis, 0.90 (0.78–1.04) between mothers who were siblings, and 1.01 (0.82–1.24) between children who were siblings. The corresponding hazard ratios of small for gestational age were 0.54 (0.52–0.56), 0.72 (0.63–0.83), and 1.02 (0.84–1.24). This suggests that the associations were partly explained by factors shared between mothers who are siblings. In conclusion, the early life circumstances of mothers appear to be important in understanding the association between education, preterm birth and small for gestational age.     

Influences on the degree of preterm birth in New South Wales

Objective : To identify risk factors for preterm birth and determine if these vary by degree of prematurity. Methods : We used data from the state‐wide mandatory surveillance system for all births in New South Wales, limiting analysis to the 836,292 live born, singleton infants without known birth anomaly born from 1994 to 2004 inclusive. Our main outcome measure was gestational age stratified into the clinically relevant groups of: ‘term’ (37–42 completed weeks gestation); ‘mildly preterm’ (33–36 weeks); ‘very preterm’ (29–32 weeks); and ‘extremely preterm’ (23–28 weeks). Analysis was by multivariate modelling using a generalised estimating equations model and confidence intervals adjusted to account for the multiple comparisons. Results : Increasing socioeconomic disadvantage was associated with increasing risk of having a preterm baby. This association strengthened with increasing degree of preterm birth, (adjusted Odds Ratio for mothers from the most disadvantaged areas having an ‘extremely preterm’ baby = 1.45 [99.67% CI 1.21–1.75] compared to least disadvantaged areas). Mothers who were older, who smoked, were Aboriginal, or had pre‐existing diabetes, hypertension, or pre‐eclampsia were independently more likely to have a preterm baby. First‐time mothers were more likely to have their baby at term. Conclusions and implications : While risk factors for preterm birth such as pre‐existing medical conditions are treatable, reducing the substantial effects of socioeconomic factors on preterm birth presents the greatest potential for change. Our data shows that tackling wider social issues will be necessary to assist in reducing the rising preterm birth rate.     

Association of Infants Small for Gestational Age with Anemia under Five Years Old in Two Large Longitudinal Chinese Birth Cohorts

Babies who are born small for their gestational age (SGA) have low iron reserves, thus probably increasing the risk of offspring anemia. We studied two longitudinal birth cohorts to evaluate the association of SGA with the risk of anemia during early childhood. Cohort 1 was recruited from five counties in northern China involving 17,180 singleton infants born during 2006–2009 and cohort 2 from 21 counties or cities in southern China involving 180,619 children born during 1993–1996. Anemia was diagnosed by hemoglobin at 6 and 12 months in cohort 1 and at 55 months in cohort 2. The overall incidences of SGA were 7.07% and 5.73% in cohort 1 and cohort 2, respectively. SGA was associated with increased anemia at 6 months (adjusted odds ratio (OR): 1.52; 95% confidence interval (CI): 1.24, 1.86) and 12 months (adjusted OR: 1.42; 95% CI: 1.13, 1.79) in cohort 1 and at 55 months (adjusted OR: 1.11; 95% CI: 1.05, 1.17) in cohort 2. The positive associations for anemia at 6, 12, and 55 months persisted in both logistics and multiple linear models. Our results support a gradually decreased association between SGA and the increased risk of childhood anemia with a longer follow-up time in infants and children.     

School attainment of children who had a single umbilical artery at birth

Lilja M. School attainment of children who had a single umbilical artery at birth. Paediatric and Perinatal Epidemiology 2010; 24: 166–170. To the best of our knowledge, this is the first registry study of school achievements among children born with a single umbilical artery (SUA). A total of 1600 infants born with SUA during 1983–86 were studied. We linked the Swedish Medical Birth Registry with the Swedish School Registry, which contains the school grades of all children in Sweden when leaving compulsory school. Risks were estimated as odds ratios (OR) using the Mantel‐Haenzel procedure, after adjustment for four potential confounders: year of birth, maternal age, parity and maternal education. There was a 60% excess of children born with SUA who did not complete compulsory school after removal of infants born preterm, small‐for‐gestational age and low Apgar score (OR = 1.60 [95% confidence interval 1.28, 2.00]). When sports and the three core school subjects (mathematics, English and Swedish) were studied, there was an increased risk for ‘not passed’ in all subjects except sport and a slight decrease in the probability of achieving ‘passed with distinction or excellence’. In the three core subjects there was an association with gender, boys with SUA being more likely to have ‘not passed’ than girls. In conclusion the children born with SUA are more likely than children born with three vessels to show impaired school achievements.     

Outcomes in preterm infants

Preterm birth is defined as birth before 37 completed weeks gestation, and it is estimated that each day, across the world over 41,000 infants are born before this gestational age. The risk of adverse consequences declines with increasing gestational age. While this paper focuses on the consequences of preterm birth, the adverse consequences for infants born at 38 and 39 weeks gestation are also of a higher risk than those for infants born at 40 weeks gestation, with the neonatal mortality risk increasing again in infants born beyond the 42nd week of gestation.     

Risk of cancer in children with the diagnosis immaturity at birth

Cancer risk in children born before term has been assessed in a large number of case-control studies but very rarely in cohort studies. We carried out a cohort study of 35 178 children with the diagnosis immaturity at birth in the Hospital Discharge Register during 1977-89. The children were followed for cancer in the Danish Cancer Registry until 1994 and comparisons were made with incidence rates for all children in Denmark. The 64 observed cases of childhood cancer in the cohort corresponded closely to the expected number {standardised incidence ratio (SIR) = 1.03; [95% confidence interval (CI) 0.80, 1.32]}. The only cancer site with an observed number that deviated significantly from the expected number was central nervous system (CNS) tumours (26 cases observed; SIR = 1.57; [95% CI 1.02, 2.30]) in particular medulloblastoma (9 cases observed; SIR = 3.1; [95% CI 1.4, 5.9]). In a nested case-control study of the CNS tumours, we found that more cases than controls had been exposed to diagnostic X-rays, but the result was not significant. Surprisingly, for those born before term, the risk of CNS tumours increased with increasing gestational age in the nested case-control data. Our results are in line with previous evidence that children born before term are not at increased risk for childhood cancer in general. An explanation behind the excess of CNS tumours could not be identified, but the effect of diagnostic X-rays in newborns may deserve further attention.     

Anthropometric measurements for neonates, 23 to 29 weeks gestation, in the 1990s

Reference data describing weight, length, and head circumference (anthropometric measurements) at birth were published by Lubchenco and Usher before 1970. Few attempts have been made to investigate whether these data are appropriate for today's cohort of preterm neonates. We analysed anthropometric data for neonates born between 23 and 29 weeks' gestation. Reference charts were developed from the measurements obtained from neonatal records, and gestational age, obtained from maternal charts, on 975 neonates delivered at four neonatal centres in Michigan during 1992 and 1997. The analysis was confined to children with gestational age that was consistent or within 7 days by last menstrual period, obstetric examination, ultrasound and neonatal determinations. At 23 to 29 weeks' gestation, ethnicity and multiple births did not have any significant impact on birthweight but girls were lighter. We compared our anthropometric charts with those presently being used at many neonatal centres. In our study, physical measurements at birth of preterm neonates born between 1992 and 1997 were significantly different from those currently used to assess growth status. Furthermore data derived from published studies that utilised birth certificates with gestational age based on last menstrual period seem to overestimate birthweight. For preterm infants, our findings are concordant with recently published values from 18 states of the US. Because of improved survival, gestational age assessment and perinatal care of preterm neonates, development of new reference anthropometric measurements for neonates is overdue. Our Michigan data of 23-29 weeks preterm provides new national reference values, which we recommend for use in US neonatal centres for extremely preterm neonates.     

Gestational age, birth weight, intrauterine growth, and the risk of epilepsy

The authors evaluated the association between gestational age, birth weight, intrauterine growth, and epilepsy in a population-based cohort of 1.4 million singletons born in Denmark (1979-2002). A total of 14,334 inpatients (1979-2002) and outpatients (1995-2002) with epilepsy were registered in the Danish National Hospital Register. Children who were potentially growth restricted were identified through two methods: 1) sex-, birth-order-, and gestational-age-specific z score of birth weight; and 2) deviation from the expected birth weight estimated based on the birth weight of an older sibling. The incidence rates of epilepsy increased consistently with decreasing gestational age and birth weight. The incidence rate ratios of epilepsy in the first year of life were more than fivefold among children born at 22-32 weeks compared with 39-41 weeks and among children whose birth weight was <2,000 g compared with 3,000-3,999 g. The association was modified by age but remained into early adulthood. Incidence rate ratios of epilepsy were increased among children identified as growth restricted according to either of the two methods. In conclusion, short gestational age, low birth weight, and intrauterine growth restriction are associated with an increased risk of epilepsy.     

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.     

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.     

A Population‐based Study of Perinatal Infection Risk in Women with and without Systemic Lupus Erythematosus and their Infants

Background

Increased risk of adverse birth outcomes is well described in women with systemic lupus erythematosus (SLE), but risk of maternal or infant infection in the peripartum period has not been well studied. We conducted a population‐based cohort study of infection risk in women with and without SLE and their infants.

Methods

Linked birth‐hospital discharge data identified 1297 deliveries to women with SLE and a 4:1 comparison cohort of deliveries to women without SLE in Washington State, 1987–2013. Maternal and infant infections during the first 30 days after delivery were identified. Relative risks (RR) and 95% confidence intervals (CI) were estimated.

Results

Women with SLE were 1.7 times more likely (95% CI 1.4, 2.0) to have an infection during the birth hospitalisation and more likely to receive antibiotics during labour (RR 1.3, 95% CI 1.1, 1.5), though there was no increased risk of chorioamnionitis in women with SLE. Infants of women with SLE had an increased risk for an infection during the birth hospitalisation (RR 2.2, 95% CI 1.3, 3.5), although the size of the difference was smaller when adjusted for gestational age (RR 1.4, 95% CI 0.9, 2.1). Risks of neonatal infection, sepsis, receipt of antibiotics, and admission to neonatal intensive care were also increased, and were also attenuated after adjustment for gestational age.

Conclusions

Women with SLE have an increased risk of peripartum infections and antibiotic exposure. Their neonates have a greater likelihood of infection, much of which is attributable to preterm birth.     

Nature or Nurture: A Systematic Review of the Effect of Socio-economic Status on the Developmental and Cognitive Outcomes of Children Born Preterm

The effect of socio-economic status (SES) on the cognitive outcome of preterm-born children is unknown. The objectives of this study were to systematically review the published literature and to report the strength and consistency of the effect of SES on the cognitive outcomes of preterm children, across different SES indicators. We conducted a literature search on MEDLINE, EMBASE, PsycINFO and Social Science Citation Index to identify English-language cohort or case–control studies published after 1990 that had reported the effect of at least one SES indicator on cognitive outcome in children born <37 weeks gestation. Fifteen studies (from a total 4,162 identified) were included. Thirteen SES indicators were evaluated [categorized as: “individual-level” (6 indicators), “family-structure” (3), “contextual” (2) and “composite” (2)]. Maternal educational level was the most frequently evaluated SES indicator (by 11/15 studies) and was most consistently associated with cognitive outcome. Maternal education below high school level was associated with severe cognitive deficiency [reported odds ratios (95 % CI) range: OR = 1.4 (1.0–1.9) to OR = 2.3 (1.2–4.5)]. A meta-analytic measure of the effect of SES was not calculated due to heterogeneity in studies. SES appears to confound the association between preterm birth and cognitive deficit and should be adjusted for in studies reporting cognitive outcome.