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Socioeconomic inequalities in very preterm birth rates.

AIMS: To investigate the extent of socioeconomic inequalities in the incidence of very preterm birth over the past decade. METHODS: Ecological study of all 549 618 births in the former Trent health region, UK, from 1 January 1994 to 31 December 2003. All singleton births of 22(+0) to 32(+6) weeks gestation (7 185 births) were identified from population surveys of neonatal services and stillbirths. Poisson regression was used to calculate incidence of very preterm birth (22-32 weeks) and extremely preterm birth (22-28 weeks) by year of birth and decile of deprivation (child poverty section of the Index of Multiple Deprivation). RESULTS: Incidence of very preterm singleton birth rose from 11.9 per 1000 births in 1994 to 13.7 per 1000 births in 2003. Those from the most deprived decile were at nearly twice the risk of very preterm birth compared with those from the least deprived decile, with 16.4 per 1000 births in the most deprived decile compared with 8.5 per 1000 births in the least deprived decile (incidence rate ratio 1.94; 95% CI (1.73 to 2.17)). This deprivation gap remained unchanged throughout the 10-year period. The magnitude of socio-economic inequalities was the same for extremely preterm births (22-28 weeks incidence rate ratio 1.94; 95% CI (1.62 to 2.32)). CONCLUSIONS: This large, unique dataset of very preterm births shows wide socio-economic inequalities that persist over time. These findings are likely to have consequences on the burden of long-term morbidity. Our research can assist future healthcare planning, the monitoring of socio-economic inequalities and the targeting of interventions in order to reduce this persistent deprivation gap.

England↗

Emmetropisation following preterm birth.

BACKGROUND/AIMS: Even in the absence of retinopathy of prematurity (ROP), premature birth signals increased risk for abnormal refractive development. The present study examined the relation between clinical risk factors and refractive development among preterm infants without ROP. METHODS: Cycloplegic refraction was measured at birth, term, 6, 12, and 48 months corrected age in a cohort of 59 preterm infants. Detailed perinatal history and cranial ultrasound data were collected. 40 full term (plus or minus 2 weeks) subjects were tested at birth, 6, and 12 months old. RESULTS: Myopia and anisometropia were associated with prematurity (p<0.05). More variation in astigmatic axis was found among preterm infants (p<0.05) and a trend for more astigmatism (p<0.1). Emmetropisation occurred in the preterm infants so that at term age they did not differ from the fullterm group in astigmatism or anisometropia. However, preterm infants remained more myopic (less hyperopic) than the fullterm group at term (p<0.05) and those infants born <1500 g remained more anisometropic than their peers until 6 months (p<0.05). Infants with abnormal cranial ultrasound were at risk for higher hyperopia (p<0.05). Other clinical risk factors were not associated with differences in refractive development. At 4 years of age 19% of the preterm group had clinically significant refractive errors. CONCLUSION: Preterm infants without ROP had high rates of refractive error. The early emmetropisation process differed from that of the fullterm group but neither clinical risk factors nor measures of early refractive error were predictive of refractive outcome at 4 years.

Anisometropia↗

Contribution of preterm delivery to perinatal mortality.

A detailed retrospective analysis was made of the records of 486 preterm infants, who accounted for 5-1% of all births during 1973 and 1974. Whereas preterm delivery did not contribute to perinatal mortality in terms of stillbirth, it outweighed all other causes in terms of early neonatal deaths. Preterm birth was responsible for 85% of the early neonatal deaths not due to lethal congenital deformities. Early neonatal mortality rates were closely linked both to gestational age and birth weight and to the reason for preterm birth. Early neonatal mortality was high (97 per 1000) when preterm labour was spontaneous, whether or not associated with material or fetal disease or with multiple pregnancy, but low (27 per 1000) when preterm delivery was elective. Preventing spontaneous preterm labour would considerably reduce neonatal mortality in our community.

England↗

Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study.

OBJECTIVE: To determine the relation between intake of seafood in pregnancy and risk of preterm delivery and low birth weight. DESIGN: Prospective cohort study. SETTING: Aarhus, Denmark. PARTICIPANTS: 8729 pregnant women. MAIN OUTCOME MEASURES: Preterm delivery and low birth weight. RESULTS: The occurrence of preterm delivery differed significantly across four groups of seafood intake, falling progressively from 7.1% in the group never consuming fish to 1.9% in the group consuming fish as a hot meal and an open sandwich with fish at least once a week. Adjusted odds for preterm delivery were increased by a factor of 3.6 (95% confidence interval 1.2 to 11.2) in the zero consumption group compared with the highest consumption group. Analyses based on quantified intakes indicated that the working range of the dose-response relation is mainly from zero intake up to a daily intake of 15 g fish or 0.15 g n-3 fatty acids. Estimates of risk for low birth weight were similar to those for preterm delivery. CONCLUSIONS: Low consumption of fish was a strong risk factor for preterm delivery and low birth weight. In women with zero or low intake of fish, small amounts of n-3 fatty acids--provided as fish or fish oil--may confer protection against preterm delivery and low birth weight.

Adult↗

Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study.

OBJECTIVE: To determine whether a short interval between pregnancies is an independent risk factor for adverse obstetric outcome. DESIGN: Retrospective cohort study. SETTING: Scotland. SUBJECTS: 89 143 women having second births in 1992-8 who conceived within five years of their first birth. MAIN OUTCOME MEASURES: Intrauterine growth restriction (birth weight less than the 5th centile for gestational age), extremely preterm birth (24-32 weeks), moderately preterm birth (33-36 weeks), and perinatal death. RESULTS: Women whose subsequent interpregnancy interval was less than six months were more likely than other women to have had a first birth complicated by intrauterine growth restriction (odds ratio 1.3, 95% confidence interval 1.1 to 1.5), extremely preterm birth (4.1, 3.2 to 5.3), moderately preterm birth (1.5, 1.3 to 1.7), or perinatal death (24.4, 18.9 to 31.5). They were also shorter, less likely to be married, and more likely to be aged less than 20 years at the time of the second birth, to smoke, and to live in an area of high socioeconomic deprivation. When the outcome of the second birth was analysed in relation to the preceding interpregnancy interval and the analysis confined to women whose first birth was a term live birth (n = 69 055), no significant association occurred (adjusted for age, marital status, height, socioeconomic deprivation, smoking, previous birth weight vigesimal, and previous caesarean delivery) between interpregnancy interval and intrauterine growth restriction or stillbirth. However, a short interpregnancy interval (< 6 months) was an independent risk factor for extremely preterm birth (adjusted odds ratio 2.2, 1.3 to 3.6), moderately preterm birth (1.6, 1.3 to 2.0), and neonatal death unrelated to congenital abnormality (3.6, 1.2 to 10.7). The adjusted attributable fractions for these associations were 6.1%, 3.9%, and 13.8%. The associations were very similar when the analysis was confined to married non-smokers aged 25 and above. CONCLUSIONS: A short interpregnancy interval is an independent risk factor for preterm delivery and neonatal death in the second birth.

Birth Intervals↗

A randomised multicentre study of human milk versus formula and later development in preterm infants.

Whether breast milk influences later neurodevelopment has been explored in non-randomised studies, potentially confounded by social and demographic differences between feed groups. Here in a strictly randomised prospective multicentre trial, Bayley psychomotor and mental development indices (PDI and MDI) were assessed at 18 months postterm in survivors of 502 preterm infants assigned to receive, during their early weeks, mature donor breast milk or a preterm formula. These diets were compared as sole enteral feeds or as supplements to the mother's expressed breast milk. No differences in outcome at 18 months were seen between the two diet groups despite the low nutrient content of donor milk in relation to the preterm formula and to the estimated needs of preterm infants. These results contrast with those reported from our parallel two centre study that compared infants randomly assigned a standard term formula or the preterm formula during their early weeks; those fed standard formula, now regarded as nutritionally insufficient for preterm infants, were substantially disadvantaged in PDI and MDI at 18 months post-term. It is shown here that infants from that study fed solely on standard formula had significantly lower developmental scores at 18 months than those fed on donor breast milk in the present study; yet the standard formula had a higher nutrient content than the donor milk. Thus, donor milk feeding was associated with advantages for later development that may have offset any potentially deleterious effects of its low nutrient content for preterm infants. As these outcome advantages were not confounded by the social and educational biases usually associated with mothers' choice to breast feed, our data add significant support to the view that breast milk promotes neurodevelopment.

Child Development↗

Use of evoked potentials in preterm neonates.

This paper has reviewed the techniques used for recording evoked potentials in the premature infant and the early developmental changes. The maturational changes in the evoked potentials, including morphological changes, and the very rapid latency changes within the first months of life, provide an invaluable means for assessing and monitoring development within the central nervous system. The maturational changes are such that normative values are requisite, and the norms must take into account both the infant's gestational age at birth as well as the postnatal age. These norms can then be used to aid in the assessment of gestational age, and whether there has or has not been normal maturational development, either in utero or during the postnatal preterm period. Evoked potentials are of increasing value clinically in preterm neonates, primarily because of the difficulty in obtaining reliable neurological evaluation of these infants. Median nerve SEPs may provide reliable information in preterm infants at risk of PVL, and when recorded in the second week of life, predict cerebral palsy. PTN SEPs seem to be even more reliable indicators of outcome, but the difficulty in obtaining them in preterm infants needs to be taken into consideration. Further study is needed in some areas, such as in apnoeic preterm babies clearly to establish the role that evoked potentials (in this case BAEPs) may have in understanding both the aetiology and the clinical course of this dysfunction. In other conditions, such as delayed intrauterine growth, that may lead to neurological sequelae, evoked potentials can provide objective CNS assessment. Evoked potentials may also prove useful in the monitoring of treatment modalities for preterm infants. The evoked potentials are a valuable adjunct in the assessment of preterm neonates and, as their value is recognised, we expect their use to increase.

Evoked Potentials↗

Long-term gastric pH monitoring for determining optimal dose of ranitidine for critically ill preterm and term neonates.

AIM: To determine the optimal doses of ranitidine for both preterm and term infants. METHOD: The effect of ranitidine treatment was measured from the long-term intraluminal gastric pH in 16 preterm (gestational age under 37 weeks) and term infants treated in neonatal intensive care. The infants received three different bolus doses of ranitidine: 0.5 mg, 1.0 mg, and 1.5 mg per kilogram of body weight to keep the intraluminal gastric pH above 4 on a 24 hour basis. RESULTS: Critically ill neonates, including very low birth weight infants, were capable of gastric acid formation, and ranitidine treatment increased the intraluminal gastric pH. The effect of a single dose lasted longer in preterm than in term infants. The time needed for reaching the maximum gastric pH was significantly longer in preterm than in term infants. The ranitidine given correlated with the duration of increased gastric pH in a dose dependent manner both in preterm and term infants. CONCLUSION: Preterm infants need significantly smaller doses of ranitidine than term neonates to keep their intraluminal gastric pH over 4. The required optimal dose of ranitidine for preterm infants is 0.5 mg/kg/body weight twice a day and that for term infants 1.5 mg/kg body weight three times a day.

Analysis of Variance↗

Iron nutritional status in preterm infants fed formulas fortified with iron.

AIMS: To prospectively evaluate the iron nutritional status of preterm infants fed either a term (0.5 mg/dl iron) or preterm (0.9 mg/dl) formulas fortified with iron after hospital discharge. METHODS: Healthy low birthweight preterm infants were randomly assigned into three groups at the time of hospital discharge. Group A were fed an iron fortified preterm formula (0.9 mg/dl iron) until 6 months corrected age; group B, a fortified term formula (0.5 mg/l iron) until 6 months corrected age group C, the preterm formula between hospital discharge and term, then the term formula until 6 months corrected age. RESULTS: Seventy eight infants were followed up to 6 months corrected age. Iron intake from formula differed significantly between the groups (A, 1.17 mg/kg/day (SD 0.32) > C, 0. 86 mg/kg/day (SD 0.40) = B, 0.81 mg/kg/day (SD 0.23); p < 0.0001). Haemoglobin concentrations were similar to those of iron sufficient preterm infants of the same postnatal age, and term infants of the same postmenstrual age (after 3 months of age). There were no significant differences in haemoglobin concentration (p = 0.391), plasma ferritin (A vs B, p = 0.322), or in the incidence of iron deficiency (A vs B, p = 0.534). CONCLUSIONS: Iron fortified formulas containing between 0.5 and 0.9 mg/dl iron seem to meet the iron nutritional needs of preterm infants after hospital discharge.

Analysis of Variance↗

Randomised trial of iodine intake and thyroid status in preterm infants.

BACKGROUND: Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula. AIM: To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study). METHOD: A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 microg/l) versus increased (272 microg/l) iodine in preterm formula. RESULTS: The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception. CONCLUSION: Calls for increased iodine content of preterm infant formulas are not justified by this study.

Female↗

Measurement of right ventricular volume in healthy term and preterm neonates.

BACKGROUND: Pulmonary hypertension is associated with worse perinatal outcomes in infants with respiratory disorders. In such infants right ventricular dysfunction may result in poor pulmonary blood flow. OBJECTIVE: To evaluate the practicability and repeatability of echocardiographic measurements of right ventricular volume in healthy term and preterm neonates, and to follow changes in right ventricular volume over the first 2 days of life. METHODS: Serial echocardiographic examinations were performed on day 0, 1, and 2 on healthy term and preterm neonates. Two methods of estimating right ventricular volume were assessed: the ellipsoid approximation and Simpson's stacked discs methods. Systolic and diastolic volumes on days 1 and 2 were compared with baseline values on day 0. Term and preterm volumes were compared at the same time points. RESULTS: Thirty five infants were recruited, 18 term and 17 preterm. Right ventricular volumes were significantly lower on day 1 and day 2 than baseline in both term and preterm infants. Median (interquartile range) end systolic and diastolic volumes for term infants on days 0, 1, and 2 were 1.04 (0.88-1.44), 0.82 (0.70-1.03), 0.92 (0.72-0.97) ml/kg and 2.21 (2.10-2.75), 2.05 (1.81-2.38), 1.91 (1.81-2.13) ml/kg respectively. In preterm infants the values were 1.09 (0.91-1.16), 0.72 (0.54-0.91), 0.61 (0.54-0.76) ml/kg and 2.09 (1.71-2.25), 1.47 (1.23-1.98), 1.43 (1.22-1.78) ml/kg respectively. CONCLUSION: Right ventricular volume decreases over the first 2 days of life in healthy term and preterm infants.

Cardiac Output↗

Use of healthcare resources, family function, and socioeconomic support during the first four years after preterm birth.

OBJECTIVES: To assess the use of healthcare resources for preterm infants and to evaluate family function and socioeconomic support in a defined population from birth to 4 years of age. METHODS: In a prospective case-control study, 39 singleton preterm infants without prenatal abnormalities born during an 18 month period were studied together with their families. The population consisted of 19 very preterm infants (less than 32 weeks) and 20 randomised moderate preterm infants (32-35 weeks), and the control group comprised 39 full term infants. Contacts with medical services, child health services, and the social welfare system were registered, and family function and life events were studied. RESULTS: The preterm children were more often readmitted to hospital (odds ratio (OR) 6.6, 95% confidence interval (CI) 2.0 to 22.1) and had more outpatient attendances (OR 5.6, 95% CI 2.1 to 15.0) during their first year of life. Mothers in the preterm group more often used temporary parental allowance than the control mothers (p < 0.001). The number of contacts with the child health services and the social welfare system did not differ significantly from the controls. Neither was there any significant difference with regard to family function or life events at 4 years of age. CONCLUSIONS: A large proportion of the premature children used specialist care during the first years of life. However, the families of the preterm infants were socially well adapted up to four years after birth compared with the control families.

Adult↗

A retrospective study of all low birth-weight preterm babies born in BMH Rinteln between 1980-1989.

A retrospective study was undertaken of all preterm babies born in BMH Rinteln between 1980-88 weighing less than 2500g. The total proportion of low birth weight babies was 7% and 58% of these were preterm (454 babies). Sixty per cent of women presented after the spontaneous rupture of membranes or in established labour. Conservative management of ruptured membranes, whilst not leading to life-threatening sepsis, did not significantly prolong pregnancy. Sixteen percent of the babies were very low birth weight (under 1500g). Delivery of these infants by Caesarean section when presenting by the breech improved survival, although this was not statistically significant. Thirty percent of all babies were delivered by Caesarean section before 36 weeks, reflecting obstetric emergencies in the mother which predisposed to preterm delivery. Neonatal survival depended on both gestational maturity and birth weight and was not significantly better in babies who were low birth weight for gestational age. These infants however represented 75% of the still-births and congenital abnormalities. Sixty percent of the mothers smoked and 50% had other identifiable risk factors for preterm delivery; 20% of the multiparous patients had previously experienced a perinatal death, preterm delivery or had a baby with intra-uterine growth retardation. It is suggested that preterm delivery is a significant problem in an Army population despite full employment, adequate housing and comprehensive medical care. Attempts to stop labour are unlikely to be successful. Effort should be made antenatally to identify those women who may be at risk of "idiopathic" preterm labour, as patient education programmes have been shown to decrease the incidence.

Adult↗

Oxidative stress in lavage fluid of preterm infants at risk of chronic lung disease.

There is evidence that oxidative stress plays a role in the development of chronic lung disease (CLD), with immature lungs being particularly sensitive to the injurious effect of oxygen and mechanical ventilation. We analyzed total ascorbate, urate, and protein carbonyls in 102 bronchoalveolar lavage fluid samples from 38 babies (33 preterm, 24-36 wk gestation; 5 term, 37-39 wk gestation). Preterm babies had significantly decreasing concentrations of ascorbate, urate, and protein carbonyls during the first 9 days of life (days 1-3, 4-6, and 7-9, Kruskal-Wallis ANOVA: P = 0.016, P < 0.0001, and P = 0.010, respectively). Preterm babies had significantly higher protein carbonyl concentrations at days 1-3 and 4-6 (P = 0.005 and P = 0.044) compared with term babies. Very preterm babies (24-28 wk gestation) had increased concentrations of protein carbonyls at days 4-6 (P = 0.056) and significantly decreased ascorbate concentrations at days 4-6 (P = 0.004) compared with preterm babies (29-36 wk gestation). Urate concentrations were significantly elevated at days 1-3 (P = 0.023) in preterm babies who subsequently developed CLD. This study has shown the presence of oxidative stress in the lungs of preterm babies during ventilation, especially in those who subsequently developed CLD.

Antioxidants↗

A comparison of preterm and adult airway smooth muscle mechanics.

To determine whether airway smooth muscle undergoes a maturational change regarding force generation, length-tension relationships were determined in isolated trachealis strips from adult and preterm sheep. At the length of maximum force generation, passive active and total tensions of the adult muscle were 2.5 times greater than preterm values (P less than 0.001). KCl stimulation yielded a greater peak tension in the adult strips than in the preterm strips (P less than 0.01). Preterm strips required higher concentrations of KCl to initiate contractions and higher concentrations to reach peak tension. Acetylcholine- (ACh) induced contraction resulted in greater force development at each dose in the adult strips compared with preterm strips (P less than 0.001). The dose of ACh required to reach a half-maximal response was significantly less for the adult strips than for the preterm strips (P less than 0.005). These data demonstrate that both force generation and receptor sensitivity increase with age. This inability of immature smooth muscle to generate as much force as adult smooth muscle may help explain why very preterm neonates requiring intermittent positive-pressure ventilation are at risk for developing structural airway problems.

Aging↗

Detection of the cervical gland area in threatened preterm labor using transvaginal sonography in the assessment of cervical maturation and the outcome of pregnancy.

OBJECTIVES: To detect the cervical gland area in threatened preterm labor, and to determine its detection rate and relationship with cervical maturation and outcome of pregnancy in preterm labor. METHODS: This was a mixed longitudinal and cross-sectional study involving 615 transvaginal scans performed to detect the cervical gland area and measure cervical length in 101 singleton pregnancies with threatened preterm labor. The patients were treated with intravenous administration of ritodrine chloride for regular uterine contractions at 16-35 weeks of gestation. 260 normal singleton pregnancies served as controls. Simultaneously conventional digital examination was used to assess the cervical maturation index. The detection rates of the cervical gland area, measurements of cervical length by sonography, and assessment of the cervical maturation index by digital examination in threatened preterm labor were compared with those of normal singleton pregnancies. In the threatened labor group, the outcome of pregnancy was assessed according to the sonographic absence or presence of the cervical gland area. RESULTS: In the normal pregnancy group, the detection rate of the cervical gland area remained practically constant until the 31st week of pregnancy (97%), but substantially decreased thereafter (70.2% in gestational weeks 32-35). In the threatened preterm labor group, the detection rate of the cervical gland area was constantly lower (44.5%) and the cervical maturation index was higher (4.65 score) than in the normal pregnancy group (83.1% and 1.80 score, respectively). The outcome of pregnancy in the threatened preterm labor group was poorer in the subgroup with the absence of a cervical gland area than in the subgroup with the presence of a cervical gland area (duration of pregnancy 257.0 vs. 271.0 days, birth weight 2,597.2 vs. 2,990.0 g, and admission to delivery interval 38.8 vs. 60.8 days). Highly significant correlations were noted among the detection rates of a cervical gland area and cervical length, cervical maturation index, and outcome of pregnancy. CONCLUSIONS: This study demonstrates for the first time that the sonographic absence of the cervical gland area reflects cervical maturation and could be considered as a predictor of threatened preterm labor and a sign of poor outcome of pregnancy in this condition.

Adolescent↗

Language development in very low birth weight preterm children: a follow-up study.

The language development of 17 very low birth weight (VLBW) preterm children was compared with that of matched controls at the ages of 2 and 4 years. At the age of 2 years, the VLBW preterm children achieved significantly lower scores in the language comprehension test than their matched controls. In addition, they used shorter and more immature sentences. At the age of 4 years, difficulties in the VLBW preterm children manifested as deficiencies in language comprehension, naming and auditory discrimination. The language test results at the age of 2 years significantly correlated with those at the age of 4 years, but mainly in the preterm group. The highest and most frequent correlations were found between the language test scores at 2 years and the auditory discrimination test scores at 4 years. The only significant correlation to be found in the control group was between the vocabulary test score at 2 years and the consonant discrimination test score at 4 years. Therefore, language development of the VLBW preterm children should be measured and monitored from toddler age onwards. Special attention should be paid to measurements of auditory processing. While the results of the present study, however, represent mainly the outcome in a group of VLBW preterm children with changes in the neonatal MRI, the results should not be generalized to all VLBW preterm children.

Brain↗

Increased level of granulocyte elastase in cervical secretion is an independent predictive factor for preterm delivery.

OBJECTIVE: The objective of this study was to explore whether increased levels of granulocyte elastase in cervical secretion is an independent predictive factor for preterm delivery before 34 weeks of gestation in the patient with preterm labor. METHODS: One hundred and sixty-one women with preterm labor at 22-28 weeks of gestation were enrolled prospectively. The level of granulocyte elastase in cervical secretions was measured by immunoassay, vaginal secretions were collected for the microscopic evaluation of Gram-stained smears, and the uterine cervix was assessed by transvaginal ultrasonography. RESULTS: Nineteen of 161 patients (12%) delivered before 34 weeks of gestation. Granulocyte elastase assessment had a sensitivity, specificity, positive predictive value, and negative predictive value for preterm delivery of 53, 75, 22 and 92%, respectively. A positive elastase assessment was associated with a relative risk for preterm delivery of 2.9 (95% CI 1.3-6.6), whereas a positive bacterial vaginosis assessment and shorter cervical length less than 25 mm demonstrated a relative risk of 1.9 (95% CI 0.8-4.6) and 1.5 (95% CI 0.6-5.0), respectively. CONCLUSION: The present study demonstrates that the risk of spontaneous preterm delivery before 34 weeks of gestation is increased in the women with preterm labor who are found to have an increased level of granulocyte elastase in cervical secretions.

Adult↗