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Preterm meconium staining of the amniotic fluid: associated findings and risk of adverse clinical outcome.

BACKGROUND: The incidence of preterm meconium staining of the amniotic fluid (MSAF) is uncertain. It may be an indicator of possible listeriosis. It is unclear how great this risk is or whether preterm MSAF is a risk factor for adverse neonatal outcome. OBJECTIVE: To investigate the incidence of preterm MSAF, the incidence of associated maternal and neonatal infection, and the outcomes of the infants at discharge. DESIGN: Retrospective case-control study. METHODS: Infants < 33 weeks gestation with preterm MSAF born in the Simpson Memorial Maternity Pavilion, Edinburgh between 1 January 1994 and 2 January 2001 were matched with the next infant of the same sex and gestation with clear liquor. Maternal and infant characteristics, culture results, placental histology, and clinical outcomes were compared. RESULTS: Preterm MSAF was observed in 45/1054 (4.3%) infants below 33 weeks gestation. No maternal or infant listeriosis was identified in cases or controls. There was no significant difference in birth weight, Apgar score, or first pH between cases and controls. Preterm MSAF was associated with prolonged rupture of the membranes (odds ratio (OR) 3.34, 95% confidence interval (CI) 1.07 to 10.49), but not maternal hypertension, sepsis, or chorioamnionitis. Severe (grade 3/4) intraventricular haemorrhage was significantly more common in infants with preterm MSAF (OR 2.03, 95% CI 1.62 to 2.53). There was no significant difference in mortality. Early onset sepsis was observed in two cases and three controls. CONCLUSIONS: Preterm meconium staining of the amniotic fluid may be associated with increased risk of intraventricular haemorrhage. It does not appear to be a useful indicator of listeriosis.

Amniotic Fluid↗

Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage.

OBJECTIVE: To find out whether women with bacterial vaginosis detected early in pregnancy are at increased risk of preterm delivery. DESIGN: Prospective description cohort study. SETTING: Antenatal clinic in a district general hospital. SUBJECTS: 783 women examined during their first antenatal clinic visit and screened for recognised risk factors for preterm delivery and the presence of bacterial vaginosis or intermediate abnormal flora detected by examination of a vaginal smear stained by Gram's method. MAIN OUTCOME MEASURES: Gestational age at delivery classified as late miscarriage (16-24 weeks' gestation), preterm delivery (24-37 weeks' gestation), term delivery (> or = 37 weeks' gestation). RESULTS: Multiple logistic analysis showed that there was an increased incidence of preterm delivery in women with a previous preterm delivery (9/24; odds ratio 25; 95% confidence interval 9 to 70; P < 0.001) and bacterial vaginosis (9/115; 2.8; 1.1 to 7.4; P = 0.04). A further logistic analysis of data from women recruited before 16 weeks' gestation showed that preterm deliveries or late miscarriages occurred more often in women with bacterial vaginosis (12/77; 5.5; 2.3 to 13.3; P < 0.001). CONCLUSIONS: Late miscarriage and preterm delivery are associated with the presence of bacterial vaginosis in early pregnancy. This is independent of recognised risk factors such as previous preterm delivery.

Abortion, Spontaneous↗

Preterm birth in twins after subfertility treatment: population based cohort study.

OBJECTIVES: To assess gestational length and prevalence of preterm birth among medically and naturally conceived twins; to establish the role of zygosity and chorionicity in assessing gestational length in twins born after subfertility treatment. DESIGN: Population based cohort study. SETTING: Collaborative network of 19 maternity facilities in East Flanders, Belgium (East Flanders prospective twin survey). PARTICIPANTS: 4368 twin pairs born between 1976 and 2002, including 2915 spontaneous twin pairs, 710 twin pairs born after ovarian stimulation, and 743 twin pairs born after in vitro fertilisation or intracytoplasmic sperm injection. MAIN OUTCOME MEASURES: Gestational length and prevalence of preterm birth. RESULTS: Compared with naturally conceived twins, twins resulting from subfertility treatment had on average a slightly decreased gestational age at birth (mean difference 4.0 days, 95% confidence interval 2.7 to 5.2), corresponding to an odds ratio of 1.6 (1.4 to 1.8) for preterm birth, albeit confined to mild preterm birth (34-36 weeks). The adjusted odds ratios of preterm birth after subfertility treatment were 1.3 (1.1 to 1.5) when controlled for birth year, maternal age, and parity and 1.6 (1.3 to 1.8) with additional control for fetal sex, caesarean section, zygosity, and chorionicity. Although an increased risk of preterm birth was therefore seen among twins resulting from subfertility treatment, the risk was largely caused by a first birth effect among subfertile couples; conversely, the risk of prematurity was substantially levelled off by the protective effect of dizygotic twinning. CONCLUSIONS: Twins resulting from subfertility treatment have an increased risk of preterm birth, but the risk is limited to mild preterm birth, primarily by virtue of dizygotic twinning.

Birth Weight↗

Spontaneous preterm delivery in primiparous women at low risk in Denmark: population based study.

OBJECTIVES: To analyse trends in preterm delivery and the factors contributing to preterm delivery in Denmark. To construct a standard population at low risk (white European, 20-40 years of age, with a singleton spontaneous pregnancy) and describe the changes in this population so that time trends can be compared internationally. DESIGN: Population based study. PARTICIPANTS: 99.8% of all deliveries in Denmark, 1995-2004. MAIN OUTCOME MEASURES: Proportion of babies born at less than 37 weeks' completed gestation for each year in the overall population and in a standard population at low risk. RESULTS: Overall, the proportion of preterm deliveries increased by 22% from 1995 to 2004. During the same period, known risk factors for preterm delivery such as in vitro fertilisation, multiple pregnancies, and elective deliveries also increased, and logistic regression analyses showed that these factors were associated with an increased risk of preterm delivery. Spontaneous preterm deliveries in primiparous women at low risk rose 51% (from 3.8% to 5.7%) during this time compared with 20% (2.7% to 3.2%) in multiparous women at low risk. CONCLUSIONS: The overall proportion of preterm deliveries increased significantly from 1995 to 2004 and primiparity and multiple birth were the most important contributing factors. The rise in spontaneous preterm deliveries in the standard population of primiparous women at low risk was greater than in the total population.

Adult↗

Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants.

BACKGROUND: The establishment of a balanced intestinal microflora which may protect against infection is desirable for the preterm infant. OBJECTIVE: To investigate the effect of a preterm formula milk supplement consisting of oligosaccharides in similar proportions to human milk on the faecal flora and stool characteristics of preterm infants. STUDY DESIGN: To resemble the effect of human milk, an oligosaccharide mixture consisting of 90% galacto-oligosaccharides and 10% fructo-oligosaccharides was used to supplement a standard preterm formula at a concentration of 10 g/l. This supplemented formula was studied in 15 preterm infants, and the results were compared with those found in 15 infants fed a formula supplemented with maltodextrin as placebo. A group fed fortified mother's milk was investigated as a reference group (n = 12). On four days during a 28 day feeding period (1, 7, 14, and 28), the faecal flora was investigated, and stool characteristics, growth, and possible side effects were recorded. RESULTS: During the study period, the number of bifidobacteria in the group fed the oligosaccharide supplemented formula increased to the upper range of bifidobacteria counts in the reference group. The difference between the supplemented and non-supplemented groups was highly significant (p = 0.0008). The stool characteristics were also influenced by the supplement: the stool frequency after 28 days was significantly lower in the control group than in the oligosaccharide supplemented group (p = 0.0079) and the reference group (p < 0.0001). Over the study period, the stool consistency in the control group became harder, but remained fairly stable in the other two groups. There was no effect of the different diets on the incidence of side effects (crying, regurgitation, vomiting) or on weight gain or length gain. CONCLUSION: Supplementing preterm formula with a mixture of galacto- and fructo-oligosaccharides at a concentration of 10 g/l stimulates the growth of bifidobacteria in the intestine and results in stool characteristics similar to those found in preterm infants fed human milk. Therefore prebiotic mixtures such as the one studied may help to improve intestinal tolerance to enteral feeding in preterm infants.

Animals↗

Epithelial modulation of preterm airway smooth muscle contraction.

To determine if epithelium from immature airways can modulate the responsiveness of smooth muscle, we studied paired trachealis muscle strips from preterm sheep. The epithelium was removed from one strip and left undisturbed in the other. Concentration-effect (CE) curves to acetylcholine (ACh), KCl, and isoproterenol were obtained. To evaluate maturational effects, responses to ACh and isoproterenol were studied in trachealis strips from adult airways. Maximal stress (Po) to ACh increased after epithelium removal in preterm (P < 0.05) but not adult strips. Epithelium removal caused a leftward shift of the ACh CE curves in both preterm and adult strips (P < 0.001) and a decrease in the dose required to achieve a one-half maximal response (ED50) in both preterm (P < 0.005) and adult strips (P < 0.05). The magnitude of the change in Po as well as in the ED50 for ACh between preterms and adults was similar. Epithelium removal did not alter either the Po or the CE curves of preterm strips stimulated by KCl. Response to isoproterenol in precontracted strips was enhanced in the presence of an intact epithelium in both groups (P < 0.05). These data demonstrate that preterm airway epithelium is able to modulate the responsiveness of smooth muscle. Additionally, the magnitude of the effect is unchanged with maturation. We speculate that damage of airway epithelium from mechanical ventilation may contribute to the increased incidence of airway hyperreactivity observed in preterm infants.

Acetylcholine↗

Changes in survival of twins delivered after twin-twin transfusion syndrome versus preterm singletons over the calendar years 1970-1994.

OBJECTIVE: The use of serial amniotic fluid volume reduction for the treatment of twin-twin transfusion syndrome (TTTS) became available about 1986 and may account for a recent increase in survival of TTTS twins. To determine whether the increase in survival has been due to advances in neonatal care rather than the advent of amnioreduction, the current study evaluated whether increases in survival of preterm TTTS twins were greater than increases in survival of preterm singletons from studies before 1986 compared to studies after 1986. METHODS: Medline literature search identified all reported cases of TTTS and all reports of severely preterm neonatal survival. Studies were divided into groups according to gestational age at birth (</=27 vs. >27 weeks) and midyear of each study (</=1986 vs. >1986). Comparison was performed of the increase in survival from pre-1986 studies to post-1986 studies between preterm singletons and TTTS twins. RESULTS: When comparing studies from before 1986 to after 1986, there was no difference in the increase in survival between preterm (>27 weeks) TTTS twins (67-92%) and preterm (>27 weeks) singletons (79-91%) (p = NS). When comparing studies from before 1986 to after 1986, there was a greater increase in survival among severely preterm (</=27 weeks) TTTS twins (0-22%) than among severely preterm (</=27 weeks) singletons (47-57%) (p = 0.036). CONCLUSIONS: Because of the paucity of data on TTTS twins and the retrospective nature of this study, conclusions are limited. There appears to be some basis for the belief that amnioreduction improves survival in TTTS twins delivered at </=27 weeks' gestation. These results confirm the need for a randomized, controlled trial of expectant management versus amnioreduction for the treatment of TTTS.

Amniotic Fluid↗

The value of interleukin-8, interleukin-6 and interleukin-1beta in vaginal wash as predictors of preterm delivery.

AIMS: To study the value of interleukin (IL)-8, IL-6 and IL-1beta in vaginal wash as predictors of preterm delivery. METHODS: A prospective analysis of a study group of 200 pregnant women between 24 and 34 weeks of gestation with intact membranes and preterm labor and a control group of 50 pregnant women during the same period of gestation. The controls had uncomplicated pregnancies and subsequently delivered at term. Samples of vaginal secretions were collected from both groups and analyzed for IL-1beta, IL-6 and IL-8 concentrations. RESULTS: Of the women in the study group, 70 had preterm deliveries, while all women in the control group had full-term deliveries. Compared with the control group, the study group had significantly higher concentrations (p < 0.021) of IL-1beta, IL-6 and IL-8. The women in the study group delivering preterm also had IL-1beta, IL-6 and IL-8 concentrations significantly greater (p < 0.001) than those of the same group delivering full term. ROC curves were used to establish cut-off points for the three interleukins to predict preterm delivery. We did not find a cut-off point with an appropriate sensitivity and specificity. CONCLUSION: The concentrations of interleukins in vaginal wash were significantly higher both in the women with preterm labor and in those delivering preterm. While values differed between controls and those with the preterm labor, no cut-off can be obtained to use the results of IL-1beta, IL-6 and IL-8 as a predictor clinically.

Female↗

Inhaled nitric oxide effects on lung structure and function in chronically ventilated preterm lambs.

RATIONALE: Inhaled nitric oxide (iNO) can reverse neonatal pulmonary hypertension and bronchoconstriction and reduce proliferation of cultured arterial and airway smooth muscle cells. OBJECTIVES: To see if continuous iNO from birth might reduce pulmonary vascular and respiratory tract resistance (PVR, RE) and attenuate growth of arterial and airway smooth muscle in preterm lambs with chronic lung disease. METHODS: Eight premature lambs received mechanical ventilation for 3 weeks, four with and four without iNO (5-15 ppm). Four term lambs, mechanically ventilated without iNO for 3 weeks, served as additional control animals. MEASUREMENTS: PVR and RE were measured weekly. After 3 weeks, lung tissue was processed for quantitative image analysis of smooth muscle abundance around small arteries (SMart) and terminal bronchioles (SMtb). Radial alveolar counts were done to assess alveolar number. Endothelial NO synthase (eNOS) protein in arteries and airways was measured by immunoblot analysis. MAIN RESULTS: At study's end, PVR was similar in iNO-treated and untreated preterm lambs; PVR was less in iNO-treated preterm lambs compared with term control animals. RE in iNO-treated lambs was less than 40% of RE measured in preterm control animals. SMart was similar in iNO-treated and both groups of control lambs; SMtb in lambs given iNO was significantly less (approximately 50%) than in preterm control animals. Radial alveolar counts of iNO-treated lambs were more than twice that of preterm control animals. eNOS was similar in arteries and airways of iNO-treated preterm lambs compared with control term lambs. CONCLUSIONS: iNO preserves structure and function of airway smooth muscle and enhances alveolar development in preterm lambs with chronic lung disease.

Animals↗

Chest wall motion in preterm infants using respiratory inductive plethysmography.

Preterm infant tidal breathing may be different from that of healthy full-term infants because of various features of the premature thorax. The purpose of this project was to describe chest wall motion in the preterm infant (gestational age <37 weeks) and compare it with chest wall motion data in a group of healthy, full-term infants. We wanted to use an objective bedside method for assessment with minimal disruption to the infant. The study population consisted of 61 preterm human infants whose mean(+/-sD) postconceptional age at time of study was 35.3+/-2.1 weeks. During the study, the infants were quietly awake in a prone position. Preterm infants had initially been admitted to a level III neonatal intensive care unit for acute management and had been transferred to a step-down area, where they were in stable condition for study. Data were collected with a semiquantitatively calibrated, noninvasive respiratory inductive plethysmograph. Mean(+/-SD) phase angle was significantly greater in preterm infants than in full-term infants (60.6+/-39.8 degrees versus 12.5+/-5.0 degrees, respectively, p < or = 0.0001). The laboured breathing index was significantly greater in preterm infants than in full-term infants (1.35+/-0.35 versus 1.01+/-0.01, respectively, p = 0.001). The ribcage contribution to breathing did not differ significantly between preterm and full-term infants (25.5+/-17.7% versus 36.3+/-14.4%, respectively, p = 0.11). These results indicate a significant increase in the degree of ribcage and abdomen asynchrony in the preterm subjects compared to the full-term infants. Plethysmography provided a time-efficient and objective method of assessing chest wall motion in this fragile population.

Female↗

Erythrocyte insulin binding in preterm newborn infants.

To characterize the erythrocyte insulin receptor in newborn infants we studied the binding of 125I-insulin to the erythrocytes from 42 preterm infants (14 at birth, 14 aged 2-7 days, and 14 aged 8-16 days) with a mean gestational age of 34.1 wk, and from 32 term infants (16 at birth and 16 aged 2-7 days). The insulin binding to cord blood erythrocytes from preterm infants was significantly higher than that of cord blood cells from term infants and to postnatal cells from preterm as well as term infants. The erythrocytes from preterm infants aged 2-7 days bound more insulin than cells from preterm infants aged 8-16 days. The maximum insulin binding (specific insulin binding at tracer concentration of insulin) correlated negatively with the gestational age both at birth and over the 1st postnatal wk. In the preterm infants there was a strong negative correlation between the maximum insulin binding and postnatal age. The enhanced insulin binding to cord blood erythrocytes from preterm infants was due to both an increased receptor concentration and a high affinity for insulin. The increased affinity persisted over the 1st wk of life. In preterm infants older than 1 wk the insulin binding characteristics were basically similar to those in term newborn infants. In all infants studied the receptor concentration seemed to be postnatal age dependent while the receptor affinity was gestational age dependent. No correlation was found between the insulin binding data and the plasma concentrations of immunoreactive insulin or C-peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Effects of low-dose dopamine infusion on cardiovascular and renal functions, cerebral blood flow, and plasma catecholamine levels in sick preterm neonates.

Effects of 2 and 4 micrograms/kg/min dopamine infusion on cardiovascular and renal functions, cerebral blood flow (CBF) and plasma catecholamine levels were studied in sick preterm neonates during the first four days of life. Preterm infants were found to have an enhanced responsiveness to the pressor effects of dopamine during this period. Comparison of the renal effects of 2 and 4 micrograms/kg/min dopamine in 61 preterm infants indicate that 2 micrograms/kg/min dopamine induces maximum diuresis and natriuresis during the first day of life provided that systemic blood pressure is within the predicted normal range. Although administration of 4 micrograms/kg/min dopamine induces further increases in blood pressure and glomerular filtration rate, urine output and sodium excretion remain similar to that on 2 micrograms/kg/min of the drug. These findings demonstrate that the direct tubular effects of dopamine play an important role in the diuretic and natriuretic action of the drug in the one-day old preterm infant. In five preterm neonates, changes in CBF transiently paralleled the dopamine-induced alterations in systemic blood pressure indicating that autoregulation of CBF is impaired but not completely ineffective in the one-day old preterm infant. In eight term neonates, increases in blood pressure had no effect on CBF. Measurements of plasma dopamine and norepinephrine levels in 14 preterm neonates and five children suggest that decreased metabolism of dopamine may contribute to the enhanced pressor responsiveness to dopamine in sick preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Diagnostic and predictive value of auditory evoked responses in preterm infants: I. Patient characteristics and long-term neurodevelopmental outcome.

The diagnostic and predictive value of brainstem, middle latency, and cortical auditory evoked responses, obtained in the neonatal period, in 81 preterm infants was assessed in relation to neurodevelopmental outcome. Eighteen healthy term infants served as a control group. In this report the patient characteristics and neurodevelopmental outcome are presented. The preterm infants were neonatally classified according to risk category and gestational age. At 5 y of age the neurodevelopmental outcome was assessed based on neurologic and neuropsychologic evaluations. The neuropsychologic test results showed the highest IQ scores in term infants, intermediate IQ scores in low risk preterm infants, and lowest IQ scores in high risk preterm infants. The intermediate IQ scores in the low risk preterm group were due to significantly lower test scores in a small subgroup of low risk preterm infants. In a post hoc analysis 12 low risk preterm infants with an unfavorable outcome could be identified. The neuropsychologic test results of the remaining low risk infants showed no clear differences compared with the term infants. The results suggest that the unfavorable outcome of the low risk preterm group as a whole is due to moderate to severe impairment of the few, rather than slight impairment of the majority.

Evoked Potentials, Auditory↗

Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies.

Thrombocytopenia (platelets <150 x 10[9]/L) is common in the early newborn period. Recent evidence suggests this is due mainly to impaired fetal megakaryocytopoiesis/platelet production. The cause remains unknown. Thrombopoietin (Tpo) is now recognized as the major regulator of platelet production in adults. However, nothing is known about Tpo levels, or the role of Tpo in megakaryocytopoiesis/platelet production, in the fetus/newborn. To answer these questions we: 1) measured plasma Tpo levels by ELISA at birth in healthy term (n = 17) and preterm (gestational age, 24-34 wk) babies (n = 16), and in thrombocytopenic preterm babies (n = 13); and 2) assessed the in vitro Tpo dose response characteristics of circulating megakaryocyte precursor cells (MKp) from all three groups. The median Tpo levels were similar in term babies 145 pg/mL (range 52-237 pg/mL) compared with preterm babies 132 pg/mL (32-318 pg/mL). In the thrombocytopenic preterm babies the median Tpo level of 185 (46-264) was not significantly higher than in healthy babies, despite the fact that their median platelet counts were significantly lower--82 x 10(9)/L (range 21-135), compared with the healthy preterm babies 252 x 109/L (152-320)--p < 0.0001. Tpo levels in the thrombocytopenic preterm babies were also much lower than levels measured in three thrombocytopenic children (905, 2138, and 2700 pg/mL). MKp from all three groups showed dose-dependent proliferation in response to Tpo (p < 0.01 at 100 ng/mL Tpo). Increases in MKp were greater in healthy and thrombocytopenic preterm babies when compared with term babies: 48.2-, 24.6-, and 9.8-fold, respectively (p < 0.05 for both comparisons). These results strongly suggest that: 1) Tpo is a major regulator of megakaryocytopoiesis/platelet production in the fetus/newborn, 2) impaired fetal Tpo production may be a factor in early thrombocytopenia in preterm babies, and 3) recombinant human Tpo is likely to be effective in the treatment of early neonatal thrombocytopenia.

Adult↗

Assessment of skeletal development in preterm and term infants by quantitative ultrasound.

Assessment of skeletal development using a nonionizing method would be desirable in critically ill preterm infants. We investigated the second metacarpus by quantitative ultrasound (QUS). Cross-sectional data were collected in 132 preterm or term infants measured within 24 h from birth and in 142 term infants up to the age of 18 mo. Longitudinal data were collected in 150 preterm infants up to the age of 14 mo. Cross-sectional data were used to devise reference curves for metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT). Both parameters increase during the last trimester of gestation. After birth, mcSOS declines up to the 6 mo and then increases up to 18 mo of life. McBTT values remain stable after birth. At birth, QUS values of preterm infants are lower than those observed at birth in term infants. In the longitudinal study, mcSOS showed a trend similar to that observed among term infants, nevertheless, values are lower up to 4-6 mo of life. Among preterm infants, mcBTT increases until it reaches values observed in term infants. Preterm infants in their first months of life have lower QUS values compared with term infants of same weight or length. This study demonstrates that it is possible to follow skeletal development and maturation by QUS in preterm infants. More specifically, the mcBTT values may provide information on bone tissue that is independent of length and weight of the preterm infant. The method here described is safe, repeatable, and reliable.

Absorptiometry, Photon↗

Prostaglandin endoperoxide H synthase (PGHS) activity and PGHS-1 and -2 messenger ribonucleic acid abundance in human chorion throughout gestation and with preterm labor.

Term and preterm parturition is associated with elevated intrauterine PG production. Although an increase of PG synthesis by the fetal membranes during term labor is well documented, there is little data available regarding the prostanoid production of these tissues at term, before the spontaneous onset of labor. In the present study, we determined the expression of PG H2 synthase (PGHS), the committing and rate-limiting enzyme of prostanoid biosynthesis, in the chorion laeve during gestation. Tissues were collected from 18 patients at term (37-41 weeks of gestation) and from 13 patients between 17 and 35 weeks of pregnancy. None of the patients were in labor. PGHS-specific activity and the abundance of messenger RNAs (mRNAs) encoding the two PGHS isoenzymes (the constitutive PGHS-1 and the inducible PGHS-2) were measured by a cell-free enzyme assay and specific ribonuclease protection assays, respectively. PGHS-specific activity as well as PGHS-1 and -2 mRNA levels were significantly (P < 0.01) higher at term before labor than earlier during gestation. Furthermore, PGHS activity at term exhibited significant positive correlation with PGHS-2 mRNA levels, but not with PGHS-1 mRNA levels. In situ hybridization indicated that the expression of both PGHS mRNAs increased in the epithelial and the mesenchymal cells of the amnion and the chorion laeve at term. Additionally, PGHS activity and mRNA levels were determined in the chorion laeve of a group of patients who gave birth spontaneously before term (30.6 +/- 1 weeks, mean +/- SEM, n = 5), and the values were compared with a group who delivered by cesarean section before labor at a similar gestational age (31.9 +/- 1.4 weeks, n = 5, P > 0.05 vs. the preterm labor group). None of the patients exhibited signs of genital tract infection. PGHS-specific activity and PGHS-1 and -2 mRNA levels were significantly higher in the preterm labor group than in the group who delivered preterm without labor. In situ hybridization suggested that the enhanced PGHS-1 and -2 mRNA expression occurred predominantly in the mesenchymal cells of the fetal membranes at preterm labor. Thus, PGHS-1 and -2 expression increases in the chorion laeve at term before labor, with PGHS-2 as the functionally prevalent isoform. This supports the possibility that PGs originating in the fetal membranes promote the onset of normal labor. Furthermore, preterm labor is associated with the elevated expression of the two PGHS isoenzymes in the chorion laeve. The maturation of the fetal membranes in preparation for term labor involves both the epithelial and the mesenchymal cells, whereas preterm labor is accompanied by the maturation of the mesenchymal tissue components, as reflected by PGHS expression. This difference may have implications in the early recognition of preterm labor.

Adult↗

Recent pharmacological advances in the treatment of preterm membrane rupture, labour and delivery.

Preterm delivery (before 37 completed weeks of gestation) is the major determinant of infant mortality. In women with a previous preterm birth associated with bacterial vaginosis, prophylactic antibiotics (e.g., metronidazole) reduce the risk of preterm birth and low birth weight. Trichomonas vaginalis increases the risk of preterm delivery, but metronidazole is not beneficial for this and may even be detrimental. Antibiotic use (e.g., erythromycin) prolongs pregnancy in late premature rupture and has health benefits for the neonate. However, antibiotics are probably not useful in preterm labour. Intramuscular 17alpha-progesterone and vaginal progesterone reduce the rate of preterm labour in high-risk pregnancies, including previous spontaneous preterm delivery. Magnesium sulfate, beta2-adrenoceptor agonists and the oxytocin-receptor antagonist, atosiban, are effective in reducing uterine contractions short-term, but there is little evidence that this leads to improved outcomes for the neonate. However, tocolysis with calcium-channel blockers does seem to lead to better outcomes for the neonate. Fetal side effects, such as ductus arteriosus constriction and impaired renal function, are associated with the inhibition of prostaglandin synthesis with indomethacin. New approaches and more effective drugs are required in the treatment of preterm delivery.

Adrenergic beta-2 Receptor Agonists↗

Three-year follow-up of vaccine response in extremely preterm infants.

OBJECTIVE: To assess whether the adequate antibody response observed in former extremely premature infants after the primary series of immunizations is sustained after the first booster vaccines. SUBJECTS AND METHODS: Sixteen former extremely premature (<29 weeks, <1000 g at birth) and 17 former full-term (>37 weeks) infants had sera obtained for antibody titer measurement at 3 to 4 years of age. All had received the primary series and first booster vaccines for diphtheria, pertussis, tetanus, polio, and Haemophilus influenzae type b. Twelve preterm and 14 full-term children had completed the hepatitis B vaccine series. RESULTS: At 3 to 4 years of age, former preterm and full-term children had similar geometric mean titer (GMT) values of antibodies to tetanus, diphtheria, and pertussis. Preterm children had a lower GMT value of Haemophilus polyribosylribitol phosphate (PRP) antibody than did full-term children (0.99 vs 3.06 microg/mL). Fifty percent of preterm and 88% of full-term children had PRP antibody >1.0 microg/mL; 100% of preterm and 94% of full-term children had anti-PRP titers >0.15 microg/mL. GMT values of neutralizing antibodies to polio serotypes 1 and 2 were similar, with 94% to 100% of both groups above protective levels (>/=1:8). The difference in GMT values of polio serotype 3 approached significance (29 vs 73); fewer preterm children had protective titer values (75% vs 100%). Among children vaccinated against hepatitis B, 75% of preterm and 71% of full-term children were protected (10 mIU/mL). CONCLUSIONS: Preterm children immunized at the recommended chronological ages displayed antibody responses similar to those for full-term children for most immunizing antigens. Responses to PRP and polio serotype 3 were less robust than those of full-term children.

Antibodies, Viral↗