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Treatment of extremely preterm infants: parents' attitudes.

AIM: To conduct a survey of the attitude towards treatment of extremely preterm infants by comparing the attitude towards life-saving treatment between a group of parents of extremely preterm children and parents in the general population. The importance the two groups of respondents assigned to parental preferences was also investigated. METHODS: A Danish national cohort of children born from 1994 to 1995 with a birthweight below 1000 g or a gestational age below 28 wk were assessed in a 5-y follow-up study including a reference group of children born at term. The parents of the children were given a sequence of case vignettes presenting different clinical situations, which formed part of a questionnaire. RESULTS: More than 80% of 222 possible index respondents and 76 possible reference respondents fulfilled the vignettes. Both groups of respondents were positive towards life-saving treatment of extremely preterm infants. The recommendations given by both groups were significantly influenced by the hypothetical child's risk of having a serious handicap and the parents' preferences. The results suggest that parents of extremely preterm children do not have a more conservative attitude towards life-saving treatment of extremely preterm infants than parents in the general population, and also support the view that parents' preferences should influence treatment decisions; although many believe that these should not be decisive. CONCLUSION: Compared to the general population, parents of children born extremely preterm did not express a more conservative attitude towards life-saving treatment of extremely preterm infants.

Adult↗

Total energy expenditure, body composition and weight gain in moderately preterm and full-term infants at term postconceptional age.

AIM: To assess total energy expenditure (TEE) and body composition, i.e. total body water (TBW) and adipose tissue volume (ATV), at term age in 8 healthy preterm infants, born between gestational weeks 30 and 33, and in 9 healthy full-term newborns. METHODS: Total and subcutaneous ATVs were assessed using magnetic resonance imaging, while TEE and TBW were estimated using doubly labelled water. RESULTS: Total ATV was 272 +/- 21 and 261 +/- 56 ml/kg body weight, while subcutaneous ATV was 88.9 +/- 1.6 and 89.7 +/- 2.0% of total ATV for preterm and full-term infants, respectively. The corresponding figures for TBW (as percentage of body weight) were 67.4 +/- 2.5 and 68.1 +/- 4.1, respectively. A significant correlation between ATV/kg body weight and body weight was found for full-term (p < 0.0001) but not for preterm infants. TEE for preterm infants was 315 +/- 20 kJ/kg body weight/24 h, which was significantly higher (p < 0.05) than TEE for full-term infants (254 +/- 45 kJ/kg body weight/24 h). At the time of investigation preterm infants weighed significantly (p < 0.05) less (540 g) than full-term infants. After the time of investigation, weight gains of preterm and full-term infants were 38 +/- 12 and 24 +/- 14 g/24 h, respectively. CONCLUSION: When compared to full-term newborns, predominantly breastfed healthy preterm infants at term postconceptional age were significantly smaller, had a similar average proportion of body fat and showed catch-up growth. Their higher TEE/kg body weight can be explained by a higher growth rate and possibly also by higher physical activity.

Adipose Tissue↗

Rooming-in for preterm infants: how far should we go? Five-year experience at a tertiary hospital.

AIM: To determine the rate of rooming-in among preterm infants born in a tertiary hospital. METHODS: We reviewed the records of all preterm infants born at our hospital during a 5-y period, 2000 to 2004. RESULTS: Of the 18 953 neonates born at our institution during this time, 1356 (7.2%) were <37 wk gestational age. Considering only preterm infants with birthweight > or =1500 g, 806 (74.1%) stayed with their mothers and 282 (25.9%) were admitted to the NICU. Of all the preterm infants that initially stayed with their mothers, 42 (5.2%) needed to be transferred to the NICU. When we stratified these preterm infants according to birthweight, we found that 29% of those <1750 g were transferred to the NICU, compared to only 5% of those > or =1750 g. CONCLUSION: Our study supports the idea that the majority of preterm infants, especially those with birthweight > or =1750 g, can safely remain near their mothers at all times during hospital stay, with both clinical and financial benefits. Neonates with birthweight <1750 g should be evaluated carefully to decide whether rooming-in is the best option. Rooming-in should be encouraged in preterm infants.

Birth Weight↗

Serum pro-hepcidin levels and relationships with iron parameters in healthy preterm and term newborns.

A recently isolated peptide hormone, hepcidin, is thought to be the principal regulator of iron homeostasis. Hepcidin acts by limiting intestinal iron absorption and promoting iron retention in reticuloendothelial cells. Its precursor peptide form is called pro-hepcidin. The aims of this study were to determine serum pro-hepcidin levels in healthy preterm and term newborns, and to assess possible relationships between pro-hepcidin and serum iron, serum ferritin, and transferrin. A serum sample was collected from each of 26 healthy preterm (gestational age < 37 weeks) and 16 healthy, full-term, appropriate-for-gestational age babies. The preterm babies were also divided into 2 subgroups based on gestational age. Samples were analyzed for complete blood count, serum iron and ferritin concentrations, iron-binding capacity, and transferrin and pro-hepcidin levels. Group findings were compared and correlations between pro-hepcidin and the iron parameters were tested. The respective serum pro-hepcidin levels (mean +/- SD) in the 16 healthy term and 26 healthy preterm newborns were 482 +/- 371.9 ng/mL and 496.7 +/- 443.5 ng/mL. Analysis revealed no significant correlations between serum pro-hepcidin level and serum iron, serum ferritin, or transferrin in the preterm or term newborns. Pro-hepcidin levels were not correlated with gestational age in the preterm group. The results indicate that healthy preterm and term newborns have high pro-hepcidin levels.

Antimicrobial Cationic Peptides↗

Dietary PUFA for preterm and term infants: review of clinical studies.

Human milk contains n-3 and n-6 LCPUFA (long chain polyunsaturated fatty acids), which are absent from many infant formulas. During neonatal life, there is a rapid accretion of AA (arachidonic acid) and DHA (docosahexaenoic acid) in infant brain, DHA in retina and of AA in the whole body. The DHA status of breast-fed infants is higher than that of formula-fed infants when formulas do not contain LCPUFA. Studies report that visual acuity of breast-fed infants is better than that of formula-fed infants, but other studies do not find a difference. Cognitive development of breast-fed infants is generally better, but many sociocultural confounding factors may also contribute to these differences. The effect of dietary LCPUFA on FA status, immune function, visual, cognitive, and motor functions has been evaluated in preterm and term infants. Plasma and RBC FA status of infants fed formulas supplemented with both n-3 and n-6 LCPUFA was closer to the status of breast-fed infants than to that of infants fed formulas containing no LCPUFA. Adding n-3 LCPUFA to preterm-infant formulas led to initial beneficial effects on visual acuity. Few data are available on cognitive function, but it seems that in preterm infants, feeding n-3 LCPUFA improved visual attention and cognitive development compared with infants receiving no LCPUFA. Term infants need an exogenous supply of AA and DHA to achieve similar accretion of fatty acid in plasma and RBC (red blood cell) in comparison to breast-fed infants. Fewer than half of all studies have found beneficial effects of LCPUFA on visual, mental, or psychomotor functions. Improved developmental scores at 18 mo of age have been reported for infants fed both AA and DHA. Growth, body weight, and anthropometrics of preterm and term infants fed formulas providing both n-3 and n-6 LCPUFA fatty acids is similar in most studies to that of infants fed formulas containing no LCPUFA. A larger double-blind multicenter randomized study has recently demonstrated improved growth and developmental scores in a long-term feeding study of preterm infants. Collectively, the body of literature suggests that LCPUFA is important to the growth and development of infants. Thus, for preterm infants we recommend LCPUFA intakes in the range provided by feeding of human milk typical of mothers in Western countries. This range can be achieved by a combination of AA and DHA, providing an AA to DHA ratio of approximately 1.5 and a DHA content of as much as 0.4%. Preterm infants may benefit from slightly higher levels of these fatty acids than term infants. In long-term studies, feeding more than 0.2% DHA and 0.3% AA improved the status of these fatty acids for many weeks after DHA; AA was no longer present in the formula, enabling a DHA and AA status more similar to that of infants fed human milk. The addition of LCPUFA in infant formulas for term infants, with appropriate regard for quantitative and qualitative qualities, is safe and will enable the formula-fed infant to achieve the same blood LCPUFA status as that of the breast-fed infant.

Breast Feeding↗

Maternal serum ferritin concentration in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the relationship between maternal serum ferritin concentrations in the second trimester and the risk of preterm delivery (PTD). METHODS: A prospective observational study was conducted. Fifty consecutive women with singleton pregnancies, who were admitted to the Maternal Fetal Medicine Unit due to preterm labor in the second trimester, were included. Maternal serum samples for determination of ferritin concentrations were obtained. Multiple logistic regression analysis was performed to control for confounders. RESULTS: Out of fifty patients enrolled in the study, 38% (19/50) delivered prematurely. Eight women (16%) had maternal serum ferritin concentrations above 30 ng/ml in the second trimester. Among them, 75% (n = 6) subsequently presented with preterm delivery (odds ratio (OR) = 6.7 with 95% confidence interval (CI) 1.1-56.2, p = 0.04). Only two patients with increased maternal ferritin concentrations delivered at term. However, 13 patients with second trimester ferritin concentrations below 30 ng/ml had preterm delivery. No significant differences in mean maternal ferritin concentrations were found between patients who delivered preterm and those that delivered at term, 31.9 +/- 50.6 vs. 13.6 +/- 15.2, respectively (p = 0.064). Using a multivariable analysis, controlling for anemia, leucocytosis and maternal age, increased serum ferritin concentrations were found to be an independent risk factor for PTD (OR = 8.6; 95% CI 1.4-52.5; p < 0.019). No significant correlation was found between serum ferritin concentrations and gestational age at birth (Pearson correlation coefficient r = -0.093; p = 0.522). CONCLUSIONS: Maternal ferritin concentrations above 30 ng/ml in the second trimester can serve as a marker for preterm delivery. However, since no correlation was found between serum ferritin concentrations and gestational age at birth, the routine use of serum ferritin as a marker for preterm delivery warrants further investigation.

Adult↗

Sonographically estimated fetal weight percentile as a predictor of preterm delivery.

OBJECTIVE: To evaluate the association between relative growth restriction and preterm birth. STUDY METHODS: Pregnant women referred for sonographic fetal weight assessments between 24 and 34 weeks of gestation were studied for gestational age at delivery. If a patient underwent more than one study, only the last one was considered. Patients with delivery induced iatrogenically or with abnormal growth patterns due to known pathology, such as maternal diabetes or fetal congenital anomaly, were excluded. A gestational age of 37 weeks or less was considered preterm and a gestational age of more than 37 weeks at delivery was considered term. Fetal weight estimation was obtained by Hadlock's formula based on biparietal diameter, femur length, and head and abdominal circumferences. The estimated fetal weight percentile was computed according to William's tables. Mean gestational age and incidence of preterm delivery for each fetal weight percentile between 1 and 100, at increments of 10, were calculated. The mean estimated fetal weight percentile, biparietal diameter, femur length, head circumferences and abdominal circumferences of preterm and term patients were compared. RESULTS: Among the 419 patients who met the inclusion criteria, duration of gestation was significantly shorter in fetuses with low estimated fetal weight percentile. The risk of preterm birth was 49% in fetuses of less than the 40th birth-weight percentile compared with a risk of 20% in fetuses of more than the 40th birth-weight percentile, representing a relative risk of 2.3. Individual fetal measurements indicate a head-sparing effect in the preterm group. CONCLUSION: Sonographically estimated fetal weight percentile measured between 24 and 34 weeks' gestation may be used as an additional and individually pertinent predictor of preterm birth.

Cohort Studies↗

Spontaneous preterm delivery in the type 1 diabetic pregnancy: the role of glycemic control.

OBJECTIVE: To determine the role of glycemic control in spontaneous preterm delivery in type 1 diabetic women. METHODS: A secondary analysis of data from women enrolled in the Diabetes in Pregnancy Program prior to 20 weeks was performed. Multiple logistic regression was used to analyze the association between glycohemoglobin A1 in women with spontaneous preterm delivery (n = 53) and women who delivered at term (n = 200). Maternal demographics and obstetric outcomes were also compared between the groups. RESULTS: Glycohemoglobin A1 levels were higher in the spontaneous preterm delivery group than the term group throughout pregnancy, reaching statistical significance after the first trimester. The last glycohemoglobin A1 prior to delivery was 8.1% in the spontaneous preterm delivery group and 7.4% in the term group (p = 0.002). Using multiple logistic regression, each 1% increase in glycohemoglobin A1 increased the risk of spontaneous preterm delivery by 37%. CONCLUSION: Poor glycemic control is associated with an increased risk of spontaneous preterm delivery, suggesting that strict glycemic control may reduce the rate of preterm delivery in these women.

Adult↗

Predictive value of transvaginal cervical length in triplet pregnancies for spontaneous preterm delivery at < or = 32 weeks.

OBJECTIVE: To establish whether cervical length is a predictor of spontaneous preterm delivery at < or = 32 weeks in triplet pregnancies. METHODS: This was a case-control study of all triplet pregnancies followed with more than three sonographic assessments of cervical length at 4-week intervals from 1995 to 2000. Cervical length in women delivered spontaneously at < or = 32 weeks (cases) was compared with that of the remaining women (controls). Statistical analysis included Fisher's exact test, chi2 test, one-way analysis of variance, logistic regression and receiver operating characteristic (ROC) curve to determine optimal cervical length thresholds for spontaneous preterm delivery at < or = 32 weeks. RESULTS: Of the 58 women included in the study, 17 (29%) delivered spontaneously at < or = 32 weeks. The preterm delivery group had similar demographic and obstetric variables, but a higher rate of cerclage placement (65% vs 17%, p < 0.001) than controls. Mean +/- standard deviation cervical length was significantly shorter among cases than controls at 16-20.0 weeks (3.0 +/- 1.2 vs. 3.9 +/- 0.8 cm, p = 0.01), but not at 20.1-24.0 weeks (3.5 +/- 1.1 vs. 3.8 +/- 1.0 cm, p = 0.76). Logistic regression analysis determined that cervical length at 16-20 weeks had an odds ratio of 0.43 (95% CI = 0.23, 0.80) for the prediction of spontaneous preterm delivery at < or = 32 weeks. ROC curve analysis identified a cervical length of < or = 2.6 cm as the optimal threshold for the prediction of spontaneous preterm delivery at < or = 32 weeks (sensitivity 41%, specificity 92%). CONCLUSIONS: In a population of triplet gestations with a 29% rate of preterm delivery, cervical length at 16-20.0 weeks, but not at 20.1-24.0 weeks, was inversely correlated with the probability of preterm delivery at < or = 32 weeks.

Adult↗

Evidence of participation of soluble CD14 in the host response to microbial invasion of the amniotic cavity and intra-amniotic inflammation in term and preterm gestations.

OBJECTIVE: Endotoxin has been implicated in the mechanism responsible for the setting of infection in preterm labor. To exert its biological effects, endotoxin binds to a circulating protein known as lipopolysaccharide binding protein (LBP) and presents endotoxin monomers to CD14, which may be a membrane-bound receptor or a soluble molecule. The endotoxin-LBP-CD14 complex interacts with Toll-like receptor 4 and other regulatory proteins leading to cellular activation and an inflammatory response. The purpose of this study was to determine whether microbial invasion of the amniotic cavity (MIAC)/intra-amniotic inflammation (both preterm and term) and parturition at term are associated with changes in the amniotic fluid and umbilical plasma soluble concentrations of CD14 (sCD14). STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 88 patients in the following groups: group 1, preterm labor with intact membranes with MIAC/intra-amniotic inflammation (n = 18) and without these conditions (n = 26); group 2, term gestations not in labor without MIAC/intra-amniotic inflammation (n = 11), in labor without MIAC/intra-amniotic inflammation (n = 12) and in labor with MIAC/intra-amniotic inflammation (n = 13); and group 3, patients who underwent genetic amniocentesis at mid-trimester (n = 8). A sample of cord blood was obtained after delivery in all patients except those in group 3. sCD14 was assayed with a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of < 0.05 was considered significant. RESULTS: sCD14 was detectable in 97% (85/88) of the amniotic fluid samples. Amniotic fluid sCD14 concentrations were lower in patients at term than in the mid-trimester of pregnancy (mid-trimester: median 482 ng/ml, range 258-838 ng/ml vs. term no labor: median 7 ng/ml, range 2-274 ng/ml, p = 0.01). Among patients with preterm labor with intact membranes, the median amniotic fluid sCD14 level of patients with MIAC/intra-amniotic inflammation was higher than in patients without these conditions (median 1568 ng/ml, range 98-5887 ng/ml vs. median 645 ng/ml, range 0-3961 ng/ml, respectively; p = 0.01). Among women at term in labor, those with MIAC/intra-amniotic inflammation had a higher median amniotic fluid sCD14 concentration than those without these conditions (median 85 ng/ml, range 2-1113 ng/ml vs. median 17 ng/ml, range 0-186 ng/ml; p = 0.01). MIAC/intra-amniotic inflammation in women with preterm labor with intact membranes was associated with a higher median umbilical venous plasma sCD14 concentration (median 744 ng/ml, range 0-3620 ng/ml vs. median 0 ng/ml, range 0-2060 ng/ml; p = 0.04). sCD14 was undetectable in plasma from umbilical cords of all neonates born to women at term. An increase in amniotic fluid concentration of sCD14 was observed in cases of intrauterine infection, not only by gram-negative bacteria, but also gram-positive bacteria and Ureaplasma spp. CONCLUSION: sCD14 is a physiological constituent of amniotic fluid, and its concentrations at term are lower than in the mid-trimester. Intrauterine infection/inflammation is associated with a higher median amniotic fluid sCD14 concentration in both preterm and term parturition. Neonates born from mothers with preterm labor with intact membranes and MIAC/intra-amniotic inflammation had a higher median concentration of sCD14 in umbilical cord plasma than those without these conditions. sCD14 concentrations are increased in the amniotic fluid and umbilical cord blood even in the absence of a microbiologically proven gram-negative infection. CD14 appears to participate in the host response to intrauterine infection even in cases involving genital mycoplasmas.

Amniocentesis↗

Maternal stress and preterm birth.

This study examined a comprehensive array of psychosocial factors, including life events, social support, depression, pregnancy-related anxiety, perceived discrimination, and neighborhood safety in relation to preterm birth (<37 weeks) in a prospective cohort study of 1,962 pregnant women in central North Carolina between 1996 and 2000, in which 12% delivered preterm. There was an increased risk of preterm birth among women with high counts of pregnancy-related anxiety (risk ratio (RR) = 2.1, 95% confidence interval (CI): 1.5, 3.0), with life events to which the respondent assigned a negative impact weight (RR = 1.8, 95% CI: 1.2, 2.7), and with a perception of racial discrimination (RR = 1.4, 95% CI: 1.0, 2.0). Different levels of social support or depression were not associated with preterm birth. Preterm birth initiated by labor or ruptured membranes was associated with pregnancy-related anxiety among women assigning a high level of negative impact weights (RR = 3.0, 95% CI: 1.7, 5.3). The association between high levels of pregnancy-related anxiety and preterm birth was reduced when restricted to women without medical comorbidities, but the association was not eliminated. The prospective collection of multiple psychosocial measures on a large population of women indicates that a subset of these factors is associated with preterm birth.

Adolescent↗

Alcohol consumption during pregnancy and the risk of preterm delivery.

The authors evaluated the association between amount and type of alcohol consumed during pregnancy and the risk of preterm delivery and whether the relation differs among very (<32 completed weeks) and moderate (from 32 to <37 completed weeks) preterm delivery. The study is based on data of 40,892 pregnant women included in the first part of the Danish National Birth Cohort. The women completed a computer-assisted telephone interview between December 12, 1997, and December 31, 2000, and delivered a liveborn singleton. Of these women, 1,880 gave birth preterm. Compared with those who abstained during pregnancy, the relative risks for preterm delivery among women who consumed from four to less than seven drinks and seven or more drinks per week during pregnancy were 1.15 (95% confidence interval: 0.84, 1.57) and 1.77 (95% confidence interval: 0.94, 3.31), respectively. Below these intake levels of alcohol, no increased risk of preterm delivery was found. Among women who consumed seven or more drinks per week, the relative risk of very preterm delivery was 3.26 (95% confidence interval: 0.80, 13.24) compared with that of nondrinkers. There were no differences in the associations between type of beverage and preterm delivery.

Adult↗

Periventricular leucomalacia and preterm birth have different detrimental effects on postural adjustments.

Postural adjustments during sitting on a moveable platform were assessed by means of multiple surface EMGs of neck, trunk and leg muscles and kinematics in three groups of children, aged 1 1/2-4 1/2 years. The first group consisted of 13 preterm children (born at a gestational age of 25-34 weeks), whose neonatal ultrasounds had shown distinct lesions of the periventicular white matter (PWM). The second group was the preterm control group, consisting of 13 preterm children with normal neonatal brain scans, matched to the PWM group with respect to gestational age at birth, birth weight, sex and age of postural assessment. The third group was formed by 13 healthy children born at term and matched to the PWM group with respect to sex and age at examination. In addition to the postural assessment an age-specific neurological examination was carried out. Three of the children of the PWM group developed a cerebral palsy syndrome, nine showed minor neurological dysfunction and one child was neurologically normal. In the preterm control group one child showed minor neurological dysfunction, while the remaining 12 children of this group and all children of the full-term group were neurologically normal. The postural assessment revealed that preterm birth was associated with two types of postural dysfunction. One dysfunction was related to the presence of a PWM lesion and consisted of a limited repertoire of response variation. The other dysfunction was not related to the presence of a PWM lesion, but to preterm birth itself. It consisted of a change in the ability to modulate the postural responses. Preterm children showed a higher sensitivity to platform velocity than full-term children, and they lacked the capacity to modulate EMG amplitude with respect to initial sitting position.

Biomechanical Phenomena↗

Seasonality of preterm births in Japan.

Seasonal variations in the proportion of preterm births in Japan from January 1979 to December 1983 are analysed using a traditional method of time-series analysis, which divides the variation in a series into trend, seasonal variation, other cyclic change, and remaining irregular fluctuations. It is shown that the proportion of preterm births in Japan have a clear seasonal periodicity with two peaks in summer and winter. Analysis of seasonality by period of gestation shows that interesting differences in kurtosis and skewness exist between summer and winter, i.e. the summer increase in preterm births was characterized by an increase of skewness which means an extension of the lower part of the distribution. On the other hand, the winter increase was characterized by a decrease of kurtosis which corresponds to a flat-topped distribution. This result suggests that causes of preterm births might be different between the two seasons. Theoretical simulations based on actual birth data in Japan over the period, are carried out to examine how season of conception could influence seasonal variations in the proportion of preterm births. Results show that, at least for first births, seasonality in conception rates could be one explanatory factor for the observed seasonal variation in proportions of preterm births. Another analysis reveals that conception in May and June are more likely to result in preterm births in Japan.

Epidemiology↗

Maternal and biochemical predictors of spontaneous preterm birth among nulliparous women: a systematic analysis in relation to the degree of prematurity.

BACKGROUND: Nulliparous women are at increased risk of spontaneous preterm birth. Other maternal and biochemical risk factors have also been described. However, it is unclear whether these associations are strong enough to offer clinically useful prediction. It is also unclear whether the predictive power of these factors varies in relation to the degree of prematurity. METHODS: The risk of spontaneous preterm birth associated with maternal characteristics and second trimester serum screening data was analysed in a dataset of 84 391 first births in Scotland between 1992 and 2001 using Cox and logistic regression. Variation in the relative risk of preterm birth over the period 24-36 weeks was assessed using a test of the proportional hazards assumption. RESULTS: The risk of spontaneous preterm birth was positively associated with maternal serum levels of alpha-fetoprotein, socioeconomic deprivation, number of previous therapeutic abortions, smoking, and being unmarried and was negatively associated with height and body mass index. The risk of preterm birth at 24-28 weeks, but not later gestations, was increased in association with maternal levels of human chorionic gonadotrophin >95th percentile, maternal age <20, and two or more previous miscarriages. The area under the receiver operating characterise curve (95% CI) for models based on these factors was 0.67 (0.63-0.71) for 24-28 weeks, 0.65 (0.62-0.68) for 29-32 weeks, and 0.62 (0.61-0.63) for 33-36 weeks. CONCLUSIONS: Time to event analytic methods can identify factors that are differentially associated with spontaneous preterm birth according to the degree of prematurity. However, models based on maternal and biochemical data perform poorly as a screening test for any degree of spontaneous preterm birth.

Adult↗

Nutrient requirements for preterm infant formulas.

Achieving appropriate growth and nutrient accretion of preterm and low birth weight (LBW) infants is often difficult during hospitalization because of metabolic and gastrointestinal immaturity and other complicating medical conditions. Advances in the care of preterm-LBW infants, including improved nutrition, have reduced mortality rates for these infants from 9.6 to 6.2% from 1983 to 1997. The Food and Drug Administration (FDA) has responsibility for ensuring the safety and nutritional quality of infant formulas based on current scientific knowledge. Consequently, under FDA contract, an ad hoc Expert Panel was convened by the Life Sciences Research Office of the American Society for Nutritional Sciences to make recommendations for the nutrient content of formulas for preterm-LBW infants based on current scientific knowledge and expert opinion. Recommendations were developed from different criteria than that used for recommendations for term infant formula. To ensure nutrient adequacy, the Panel considered intrauterine accretion rate, organ development, factorial estimates of requirements, nutrient interactions and supplemental feeding studies. Consideration was also given to long-term developmental outcome. Some recommendations were based on current use in domestic preterm formula. Included were recommendations for nutrients not required in formula for term infants such as lactose and arginine. Recommendations, examples, and sample calculations were based on a 1000 g preterm infant consuming 120 kcal/kg and 150 mL/d of an 810 kcal/L formula. A summary of recommendations for energy and 45 nutrient components of enteral formulas for preterm-LBW infants are presented. Recommendations for five nutrient:nutrient ratios are also presented. In addition, critical areas for future research on the nutritional requirements specific for preterm-LBW infants are identified.

Child Development↗

Evaluation of the tocolytic effect of a selective cyclooxygenase-2 inhibitor in a mouse model of lipopolysaccharide-induced preterm delivery.

The inflammatory process is known to cause preterm delivery. Recently, a cyclooxygenase (COX)-2 inhibitor has been developed as an anti-inflammatory drug with few side-effects. We evaluated the COX-2 inhibitor, Celecoxib, for its tocolytic effects and side-effects on dams and pups using a lipopolysaccharide (LPS)-induced preterm delivery mouse model (preterm delivery rates; 95%). With administration of Celecoxib (50, 10, 1 and 0.3 mg/kg), the preterm labour rate was significantly reduced to 18, 30, 36 and 60% respectively. The prostaglandin F(2alpha)(PGF(2alpha)) and PGE(2) concentrations in murine uterine tissue 4 and 10 h after LPS treatment with Celecoxib (10 and 1 mg/kg) were significantly lower than those in the LPS-treated group without CELECOXIB: With administration of 10 or 100 mg/kg Celecoxib, the fetal ductus arteriosus was constricted significantly in preterm and near-term rats, although constriction rates in preterm rats were significantly lower than those in near-term rats. Reproductive and renal functions in offspring whose mothers were treated with LPS and Celecoxib were normal. These data demonstrate that Celecoxib could be used as a new therapy for preterm labour. However, careful attention to constriction of the fetal ductus arteriosus should be given.

Animals↗

Maternal nutrition and spontaneous preterm birth.

Previous studies suggesting that maternal undernutrition increases the risk of preterm birth have suffered from several methodological shortcomings, including use of total gestational weight gain rather than net rate of gain in maternal tissue, inclusion of induced preterm deliveries, and error-prone gestational age measurements based solely on menstrual dates. The authors have attempted to overcome these shortcomings by investigating the potential etiologic roles of prepregnancy body mass index, net rate of maternal weight gain, height, and a number of other potential biological and sociodemographic determinants of spontaneous (i.e., noninduced) preterm birth in a cohort of 13,102 women with early ultrasound-confirmed gestational age who delivered at the Royal Victoria Hospital in Montreal, Quebec, Canada, between January 1, 1980 and March 31, 1989. Total weight gain, but not body mass index, was highly significantly associated with spontaneous preterm birth, averaging 14.6, 12.5, 9.9, and 9.1 kg, in women delivering at 37 or more, less than 37, less than 34, and less than 32 completed weeks, respectively. Although the relation persisted when weight gain was expressed as an overall rate, it disappeared when the analysis was based on net rate; mean net rates of gain were 0.28, 0.29, 0.27, and 0.27 kg/week, respectively. On the basis of multiple logistic regression analyses, significant determinants of birth at less than 37 weeks included maternal short stature; noncompletion of high school; unmarried status; smoking; diabetes; urinary tract infection within 2 weeks of delivery; prepregnancy hypertension; severe pregnancy-induced hypertension; and previous history of preterm delivery, low birth weight, or neonatal death. Most of these factors retained their significance for birth at less than 34 and less than 32 weeks. In fact, the effect of low maternal education was even stronger at these more severe "levels" of preterm birth. The authors conclude that prepregnancy weight-for-height and gestational weight gain are not important determinants of spontaneous preterm birth and that some previous studies have mistaken an effect of shortened gestation for its cause. Other biologic and social determinants, however, indicate priorities for future research and intervention.

Adult↗