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PubMed1995

Amniotic fluid interleukin-10 concentrations increase through pregnancy and are elevated in patients with preterm labor associated with intrauterine infection.

OBJECTIVE: To better understand the role of the antiinflammatory cytokine interleukin-10 in preterm labor and infection, we evaluated the amniotic fluid interleukin-10 concentrations through pregnancy, in term, and in preterm labor. STUDY DESIGN: Amniotic fluid interleukin-10 levels were measured in 147 women throughout pregnancy including patients in the second trimester, patients at term with and without labor, and in patients in preterm labor with and without an intrauterine infection. We compared the amniotic fluid interleukin-10 concentrations among these five groups using the Mann-Whitney U test. RESULTS: Amniotic fluid interleukin-10 was detected in 70% to 91% of patients in each of the five study groups. Higher concentrations were found at term compared with the second trimester (p < 0.001) and concentrations were significantly greater in patients with preterm labor and intrauterine infection compared with those patients in preterm labor without infection (p < 0.001), patients at term in labor (p < 0.001), or patients at term not in labor (p < 0.001). When the patients in preterm labor with infection were analyzed by gestational age, those patients at < 30 weeks had significantly higher amniotic fluid concentrations of interleukin-10 (p = 0.014). CONCLUSIONS: Interleukin-10 was present in the amniotic fluid of the majority of pregnancies, with higher concentrations found at term compared with the second trimester. Intrauterine infection was associated with significantly increased concentrations, with even higher concentrations found in the very premature pregnancies. Interleukin-10 has a prominent yet undefined role in pregnancy and preterm labor complicated by intrauterine infection.

Amniotic Fluid↗

PubMed1995

Idiopathic preterm deliveries in Denmark.

OBJECTIVE: To characterize and quantify various demographic factors in idiopathic preterm delivery. METHODS: All women with a permanent address in Denmark and a singleton pregnancy who gave birth to a preterm infant in 1982 (N = 51,851) were included. The material was obtained by a linkage of the Medical Birth Register and the National Register of Hospital Discharges, using personal identification numbers. RESULTS: The incidence of singleton preterm delivery was 4.5% (N = 2330), of which 67% (N = 1557) were idiopathic. The neonatal mortality rate was significantly lower with idiopathic than with indicated preterm birth. Following stepwise logistic regression analysis, age under 20 (adjusted odds ratio [OR] 1.63, 95% confidence interval [CI] 1.07-2.47; P < .03), age above 30 (adjusted OR 0.74, 95% CI 0.60-0.90; P < .004) and being married (adjusted OR 0.63, 95% CI 0.43-0.94; P < .03) correlated with idiopathic preterm birth. CONCLUSION: Idiopathic preterm birth is more common in single, young women and is associated with a lower neonatal mortality rate than indicated preterm birth.

Adult↗

PubMed1995

Single transvaginal sonographic measurement of cervical length early in the third trimester as a predictor of preterm delivery.

OBJECTIVE: To evaluate the accuracy of a single sonographic measurement of cervical length early in the third trimester as a predictor of preterm delivery. METHODS: A total of 771 women attending the antenatal clinic at the Maharaj Nakorn Chiang Mai Hospital between January 1, 1990, and November 30, 1993, with singleton gestations, cervical competence, accurate dates of last menstrual period, and gestational ages between 28-30 weeks, were recruited into the study. Forty-one were excluded, ten because of induced preterm delivery, 24 because of measurement problems, and seven because they were lost to follow-up. We analyzed the remaining 730 women. RESULTS: Ninety-one (12.5%) women ended with preterm births and the remaining 639 (87.5%) delivered at term. The mean (+/- standard deviation) cervical lengths of the term and preterm groups were statistically significantly different at 37 +/- 5 and 34 +/- 6 mm, respectively (P < .001). The likelihood ratio of cervical length at various cutoff points was calculated. The appropriate cutoff point based on the receiver operating characteristic curve (35 mm) was associated with a significantly increased likelihood of preterm delivery (20 versus 7%) and was detected in two-thirds of preterm births. This cutoff point gave a sensitivity and specificity of 65.9 +/- 5.1% (95% confidence interval [CI]) and 62.4 +/- 5.2% (95% CI), respectively. CONCLUSION: A single transvaginal sonographic measurement of cervical length at 28-30 gestational weeks can be used to predict the risk of preterm delivery, using a cutoff point of 35 mm, but its cost-effectiveness should be assessed further.

Adult↗

PubMed1995

Maternal anthropometry and idiopathic preterm labor.

OBJECTIVE: To assess the etiologic role of maternal short stature, low pre-pregnancy body mass index (BMI), and low rate of gestational weight gain in idiopathic preterm labor. METHODS: We carried out a three-center case-control study of 555 women with idiopathic onset of preterm labor (before 37 completed weeks), including two overlapping (ie, nonmutually exclusive) subsamples: cases with early preterm labor (before 34 completed weeks) and cases with recurrent preterm labor (before 37 completed weeks plus a history of prior preterm delivery or second-trimester miscarriage). Controls were matched to cases by race and smoking history. All subjects responded in person to questions about height, pre-pregnancy weight, gestational weight gain, and obstetric and sociodemographic histories. RESULTS: Maternal height, pre-pregnancy weight, and gestational weight gain demonstrated excellent test-retest reliability, with intra-class correlation coefficients of 0.97, 0.99, and 0.91, respectively. Based on matched analyses, women with a height of 157.5 cm or less had an increased risk of idiopathic preterm labor (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.25-2.74), as did those with a pre-pregnancy BMI less than 19.8 kg/m2 (OR 1.63, 95% CI 1.09-2.44) or a gestational weight gain rate less than 0.27 kg/week (OR 1.74, 95% CI 1.16-2.62). Conditional logistic regression models containing all three anthropometric variables and controlling for parity, marital status, language, age, and education yielded virtually identical point estimates and CIs. CONCLUSION: Maternal short stature, low pre-pregnancy BMI, and low rate of gestational weight gain may lead to shortened gestation by increasing the risk of idiopathic preterm labor.

Anthropometry↗

PubMed1996

Excess males in preterm birth: interactions with gestational age, race, and multiple birth.

OBJECTIVE: To confirm an excess of males among preterm births and study its interaction with other risk factors to better understand its potential etiologic significance. METHODS: Fetal gender was analyzed in 1,781,960 white and 103,329 black singleton births, and in 37,429 white twin births using vital statistics data from the six New England states for 1977-1988. RESULTS: A 7.2% excess of males was found among white singleton preterm births. There was only a 2.8% excess among comparable blacks, a highly significant difference between the races (P < .001). The effect was roughly constant for 20-37 weeks' gestation. Being married increased the effect for white, but not black, women, and was also found among white fetal deaths. Among white twins, male excess in preterm births occurred only in 20-33 week's gestations. CONCLUSIONS: Male fetal gender is associated with singleton preterm birth, an effect most evident in white women, particularly if married. Among preterm white twins, there is also a male excess, limited to gestations under 34 weeks. The excess of males in selected groups suggests the existence of a mechanism of preterm birth influenced by fetal gender. Preterm births in blacks and in twin gestations greater than 33 weeks may be more often due to alternative mechanisms that are independent of fetal gender.

Female↗

PubMed1996

Uterine allergy: a cause of preterm birth?

OBJECTIVE: To identify the origin of eosinophils in cases of eosinophil-associated preterm delivery. METHODS: From an established set of 465 consecutive non-anomalous singleton infants delivered at 22-32 weeks' gestation, we retrieved 161 cases of preterm delivery following spontaneous onset of preterm labor, 78 cases with maternal preeclampsia, 33 cases of abruption, and 193 cases of premature rupture of membranes (PROM). Charts were reviewed, and the placenta, umbilical cord, and membranes were examined histologically. In cases with extravascular eosinophils showing evident gradient toward the amniotic cavity, the origin of the eosinophils (fetal or maternal) was determined by the proximity to fetal or maternal vessels. RESULTS: Histologic evidence of an eosinophilic gradient toward the amniotic cavity was present only in the fetal (including umbilical cord and chorion) compartments. This eosinophilic gradient was present in 19% (90 of 465) of preterm delivery cases and was significantly more common in cases of PROM (54 of 193, 28%) and preterm labor (34 of 161, 21%) than abruption (two of 33, 6%) and preeclampsia (none of 78) (P < .001). In 84 of 90 cases (93%), the eosinophilic gradient was present along with multiple histologic indicators of acute intrauterine inflammation. CONCLUSION: An eosinophilic gradient toward the amniotic cavity, present in nearly a fifth of cases of preterm delivery, is probably of fetal origin, making it unlikely that a maternal "allergy-like" mechanism is a cause of preterm delivery.

Abruptio Placentae↗

PubMed1996

The association between maternal serum alpha-fetoprotein and preterm birth, small for gestational age infants, preeclampsia, and placental complications.

OBJECTIVE: To determine whether high levels of serum alpha-fetoprotein (AFP) predict increased risk of adverse pregnancy outcomes, including preterm birth (before 37 weeks), preterm birth occurring at or before 28 weeks, small for gestational age (SGA) infant, preeclampsia, and placental abnormalities, and to determine whether low levels of serum AFP predict increased or decreased risk of these outcomes. METHODS: Using the mother's first name, last name, and zip code, we linked the records of 51,008 women who participated in the California Alpha-Fetoprotein Screening Program between June 15, 1986, and October 31, 1987, with California birth certificates for singleton infants born in 1987. The accuracy of the data linkage was confirmed by manually examining complete names, mother's ethnicity, and mother's age for a sample of 500 of the mother-infant linkages. Blood samples were obtained at 15-19 weeks. RESULTS: A strong gradient of increasing risk of preterm birth with increasing levels of serum AFP was observed (test for trend, P < .01). Among women with high levels of serum AFP (at least 2.5 multiples of the median [MoM]), 24.3% had preterm births, compared with 3.8% of women with low levels of serum AFP (0.81 MoM or less), odds ratio 8.7, 95% confidence interval 7.1-10.7). This gradient persisted when preterm infants of 28 weeks or less were examined separately. Similar gradients were observed for the risk of preeclampsia and placental abnormalities. There was a weaker U-shaped relation between serum AFP level and the risk of an SGA infant. CONCLUSION: Low levels of second-trimester maternal serum AFP are associated with a very low risk of preterm birth, preeclampsia, and placental complications. High levels of serum AFP are strongly associated with preterm birth, preeclampsia, and placental abnormalities. There is a modest association between AFP levels (both low and high) and SGA birth.

Adolescent↗

PubMed1990

Preterm and early postterm motor behaviour in low-risk premature infants.

The development of spontaneous motility and posture was studied longitudinally in 14 carefully selected low-risk preterm infants. The aim of this investigation was to provide a set of data suitable for comparison with fetuses and with neurologically abnormal preterm infants. The infants were videorecorded weekly, for one hour in a supine position, from birth until their discharge from the hospital. Ten of them were thereafter also observed at home at 3-week intervals from 3 to 18 weeks of corrected age, together with 10 healthy fullterm infants. Occurrence and duration of motor patterns and postures in periods of rest and activity were obtained by off-line analysis of the videotapes. Few significant changes were found from birth until term age in the composition and quantity of the spontaneous movement patterns. Only twitches and stretches during activity periods showed a small decline approaching term age. However, notable inter-individual differences and intra-individual fluctuations from week to week were observed. Postterm development of preterm infants was similar to that of the fullterms. Both showed considerable changes in the qualities of general movements after the first postterm weeks. Only fidgety character movements occur earlier in preterm infants. No age-specific preference postures of the limbs were found in the preterm period. Midline position of the head in supine was observed at about the same postterm age in preterm and fullterm groups. Asymmetrical tonic neck postures were very inconsistently present before term age and rapidly disappeared after term, earlier so in preterm infants.

Activity Cycles↗

PubMed1992

The effect of preterm birth on brainstem, middle latency and cortical auditory evoked responses (BMC AERs).

Recent studies on the maturation of auditory brainstem evoked responses (ABRs) present conflicting results, whereas only sparse reports exist with respect to the maturation of middle latency auditory evoked responses (MLRs) and auditory cortical evoked responses (ACRs). The present study reports the effect of preterm birth on the maturation of auditory evoked responses in low risk preterm infants (27-34 weeks conceptional age). The ABRs indicate a consistent trend towards longer latencies for all individual ABR components and towards longer interpeak latencies in preterm infants. The MLR shows longer latencies for early component P0 in preterm infants. The ACRs show a remarkable difference between preterm and term infants. At 40 weeks CA the latencies of ACR components Na and P2 are significantly longer in term infants, whereas at 52 weeks CA the latencies of the same ACR components are shorter in term infants. The results support the hypothesis that retarded myelination of the central auditory pathway is partially responsible for differences found between preterm infants and term infants with respect to late ABR components and early MLR component P0. Furthermore, mild conductive hearing loss in preterm infants may also play its role. A more complex mechanism is implicated to account for the findings noted with respect to MLR component Na and ACR components Na and P2.

Evoked Potentials, Auditory↗

PubMed1993

Growth and body composition of preterm, small-for-gestational-age infants at a postmenstrual age of 37-40 weeks.

In order to understand the nutritional status of preterm, small-for-gestational-age (SGA) infants in the early postnatal period, the growth and body composition of preterm, SGA infants was followed prospectively from birth to the postmenstrual age of 37-40 weeks. The infants were stratified into different groups by gestational age, clinical condition and body proportionality. In each subgroup, the growth and changes in body composition of SGA infants were compared with appropriate-for-gestational-age (AGA) infants of a comparable postmenstrual age. At birth, the SGA infants of both the 31-33 and 34-36 week gestational-age groups were smaller than AGA infants in all body measurements, including arm area (AA), arm muscle area (AMA) and arm fat area (AFA). When the preterm SGA infants had grown to the postmenstrual age of 37-40 weeks, the amount of fat they had accumulated was as much as, or more than that in term AGA infants. Yet, they had less muscle mass and their body weight, body length and head circumference were less than those in term AGA infants. This pattern of growth and the changes in body composition had been persistently observed in SGA infants of different gestational-age groups, different clinical status and different body proportionality. Differences between postnatal enteral nutrition and placental nutrition, or different energy utilization, in preterm SGA infants are hypothesized to account for these observations. The growth of less mature (31-33 weeks gestation) SGA infants and those preterm SGA infants with an eventful clinical course was suboptimal as compared with other SGA infants in the same subgroup. In this study, the weight to length ratio (WLR) was used to define the status of nutrition in preterm SGA infants: WLR < or = 2 S.D. or > 2 S.D. off the reference mean. Infants in both groups showed some catch-up growth in body weight. Yet, at near-term their body weight were still more than 2 S.D. below the mean of term AGA. In each gestational-age group, the growth of these two body-proportionality groups did not differ from each other except for the low WLR group of 34-36 weeks gestation which had a significantly lower body weight and skinfold thickness than the group with a normal WLR. Multiple regression analysis revealed that skinfold measurements of preterm SGA infants at birth is the best factor for determining the body weight gain at near-term. After use of the skinfold thickness was set aside, WLR became the most important factor.(ABSTRACT TRUNCATED AT 400 WORDS)

Anthropometry↗

PubMed1996

Long-chain polyunsaturated fatty acid content in Dutch preterm breast milk; differences in the concentrations of docosahexaenoic acid and arachidonic acid due to length of gestation.

Recognizing the important role of long-chain polyunsaturated fatty acids (LCP) particularly in preterm infant nutrition, we studied the fatty acid composition of breast milk from 65 mothers of very preterm ( < 31 weeks of gestation) and preterm ( > or = 31 and < 36 weeks of gestation) infants. Fatty acids were determined as fatty acid methyl esters by capillary gas chromatography. In accordance with other studies, the increase of capric acid, lauric acid and myristic acid during lactation is influenced by prematurity. Unsaturated fatty acids had the inclination to decrease. Our interest was mainly focused on docosahexaenoic acid (DHA) and arachidonic acid (AA). Accelerated brain growth during the last trimester of gestation requires an extra need for these LCPs. In our study, preterm milk after a gestation period of at least 32 weeks contained the highest amounts of DHA and AA. The Western maternal diet is considered to be low in omega 3 fatty acids, that is why the concentration of DHA in our preterm milk can be regarded as a low amount. As it is the milk of their mothers, and because the amounts are higher than normally found in Western full term breast milk, the contribution of DHA to preterm milk fat (0.34%) might be considered, for the time being, as a safe natural guideline for formulas for preterm infants.

Arachidonic Acid↗

PubMed2004

Can shortened midtrimester cervical length predict very early spontaneous preterm birth?

OBJECTIVE: The study was undertaken to test the hypothesis that shortened midtrimester cervical length is more predictive of early (<26 weeks) than later (26-34 weeks) spontaneous preterm birth. STUDY DESIGN: This is a secondary analysis of a blinded, multicenter observational study of 183 women with a prior preterm birth. Vaginal sonography was begun at 16 to18 weeks' gestation and scheduled every 2 weeks (maximum 4 scans per patient). Cervical length and any observed dynamic shortening were recorded at each visit to determine the shortest observed cervical length from 16 to 24 weeks' gestation. The shortest cervical length measurements were categorized as less than 25 mm, 25 to 29 mm and 30 mm or greater. The initial cervical length was also compared with the shortest cervical length to categorize patients on the basis of the timing of cervical shortening 30 mm or less. Contingency table, linear regression, and survival analysis were used to analyze the relationship between cervical length groups and spontaneous preterm birth. RESULTS: In both the less than 25 mm and 25 to 29 mm groups, the incidence of spontaneous midtrimester birth (<26 weeks) was higher than the incidence of later (26-34 weeks) preterm birth (<25 mm group: 37% vs 19%; 25-29 mm group: 16% vs 3%, respectively) as compared with women with a shortest cervical length 30 mm or greater, who had rates of 1% and 9% respectively (P <.0001). Similarly, women who had an initial cervical length 30 mm or less and those who shortened their cervix to 30 mm or less before 22 weeks were also more likely to experience a midtrimester than later preterm birth, whereas women who shortened their cervix 30 mm or less later (22-24 weeks) or who maintained a cervical length greater than 30 mm had lower rates of midtrimester than later preterm birth (P <.0001). CONCLUSION: Shortened cervical length in the midtrimester preferentially predicts early, as opposed to later, spontaneous preterm birth in high-risk women.

Adult↗

PubMed2005

Dose response of RU486 in a novel rabbit model of noninfectious preterm birth: comparative efficacy of 3 routes of administration.

OBJECTIVE: The purpose of this study was to examine whether the pregnant rabbit model can be used as a viable model for the study of non-infection-mediated preterm birth. STUDY DESIGN: Timed pregnant New Zealand rabbits were injected with a single dose of RU486 on day 22 of gestation. Three doses (50 mg, 75 mg, and 100 mg) were administered intramuscularly, intraperitoneally, or subcutaneously. The rabbits were monitored for preterm delivery. Progesterone, cortisol, and cytokine levels were examined before the induction and after delivery. Uterine and cervical progesterone, cortisol, and cytokine levels were determined after delivery. RESULTS: RU486 resulted in 100% preterm delivery in all doses and modes of administration, compared with 0% of controls. Intramuscular administration appeared to generate the most favorable preterm delivery time. Rabbits that received 100 mg RU486 intramuscularly showed significantly decreased serum progesterone levels and uterine progesterone levels, compared with 100 mg subcutaneously and intraperitoneally. CONCLUSION: RU486 that was administered intramuscularly appears to be a potent and effective method for inducing preterm birth. This model of hormonally mediated preterm birth might serve as a useful model for the investigation of the possible mechanisms of preterm labor.

Abortifacient Agents, Steroidal↗

PubMed2006

Interconceptional antibiotics to prevent spontaneous preterm birth: a randomized clinical trial.

OBJECTIVE: We hypothesized that upper genital tract microbial infection associated with spontaneous preterm birth may precede conception. Our objective was to estimate if antibiotic administration during the interpregnancy interval in nonpregnant women with a previous preterm birth before 34 weeks' gestational age would reduce the rate of spontaneous preterm birth in the subsequent pregnancy. STUDY DESIGN: Women with a spontaneous preterm birth < 34 weeks' gestational age were randomized at 4 months' postpartum to receive oral azithromycin 1 g twice (4 days apart) plus sustained-release metronidazole 750 mg daily for 7 days, or identical-appearing placebos. This regimen was repeated every 4 months until the subsequent pregnancy. RESULTS: A total of 241 women were randomized; 124 conceived a subsequent pregnancy and were available for study, including 59 in the antibiotic group and 65 in the placebo group. In the antibiotic versus placebo group, neither subsequent spontaneous preterm birth (< 37 weeks: 52% vs 46%, P = .568; < 35 weeks: 40% vs 30%, P = .276; < 32 weeks: 31% vs 23%, P = .376) nor miscarriage (< 15 weeks: 12% vs 14%, P = .742) was significantly different. Although not statistically significant, mean delivery gestational age in the subsequent pregnancy was 2.4 weeks earlier in the antibiotic versus placebo group (32.0 +/- 7.9 vs 34.4 +/- 6.3 weeks, P = .082), and mean birth weight was lower in the antibiotic group (2046 +/- 1209 vs 2464 +/- 1067 g, P =.060). CONCLUSION: Intermittent treatment with metronidazole plus azithromycin of nonpregnant women with a recent early spontaneous preterm birth does not significantly reduce subsequent preterm birth, and may be associated with a lower delivery gestational age and lower birth weight.

Adult↗

PubMed2006

A rapid MMP-8 bedside test for the detection of intra-amniotic inflammation identifies patients at risk for imminent preterm delivery.

OBJECTIVE: Matrix metalloproteinase-8 (MMP-8) is an enzyme that is released during neutrophil activation. MMP-8 amniotic fluid concentrations are elevated not only in patients with intra-amniotic infection, but also in patients with negative amniotic fluid cultures who deliver preterm neonates. The objective of this study was to determine whether the results of a rapid MMP-8 bedside test predict imminent preterm delivery. This test can be performed in 15 minutes and without laboratory equipment. STUDY DESIGN: Amniotic fluid was retrieved from 331 patients admitted with increased preterm uterine contractions and intact membranes who met the inclusion criteria. Amniotic fluid was processed for microbial cultures, Gram stain, glucose concentration, and white blood cell count. Amniotic fluid samples were stored, and the MMP-8 rapid test was performed after delivery. End points included spontaneous preterm delivery within 48 hours, 7 days, and 14 days. Diagnostic indices, predictive values, and likelihood ratios were calculated. RESULTS: The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days was 11.6% (38/327), 20.2% (66/327), and 24.5% (80/327), respectively (4 patients with augmentation of labor were excluded). A positive MMP-8 rapid test had a positive predictive value of 70% (23/33) for the identification of patients who delivered spontaneously within 48 hours, and 94% (31/33) for patients who were delivered within 7 days and 14 days (likelihood ratios: 17.5 [95% CI, 9-33.9], 61.3 [95% CI, 15.1-250], and 50 [95% CI, 12-196], respectively). CONCLUSION: The MMP-8 rapid test can identify patients at risk for preterm delivery within 7 days and 14 days. Moreover, a positive MMP-8 rapid test result can identify patients with intra-amniotic infection/inflammation with a high sensitivity and specificity. This rapid test will give clinicians a fast and accurate assessment of the inflammatory status of the amniotic cavity and allow for better identification of patients at risk for impending preterm delivery.

Adult↗

PubMed2005

Hyperactivity in adolescents born very preterm is associated with decreased caudate volume.

BACKGROUND: Several studies have associated preterm birth with impaired behavioral functioning and attention problems. In addition, preterm individuals have an increased risk of brain injury in the neonatal period. Such early lesions have the potential to disrupt subsequent neurodevelopment. This study explored behavioral functioning, particularly externalizing behavior, in a group of adolescents who were born very preterm and its relationship with volume of the caudate, a brain region particularly vulnerable to damage in the preterm neonate. METHODS: We studied 72 adolescents born before 33 weeks and 50 age- and gender-matched full-term control subjects. Behavioral assessment included the Rutter Behavioural Scale and a social adjustment scale. Bilateral caudate volumes were quantified by stereologic methods. RESULTS: Preterm adolescents scored significantly higher than control subjects on the Rutter hyperactivity score, and boys scored higher than girls. In preterm boys only, left caudate volume was negatively correlated with hyperactivity score (r = -.43, p = .018) and social adjustment score in childhood (r = -.40, p = .028). CONCLUSIONS: Our data suggest that boys born very preterm are more likely to experience nonclinical behavioral problems in adolescence compared with full-term control subjects. Our results indicate that behavioral problems in this group might be associated with reductions in volume of the left caudate nucleus.

Adolescent↗

PubMed2004

Cell proliferation correlates with the postconceptual and not with the postnatal age in the hippocampal dentate gyrus, temporal neocortex and cerebellar cortex of preterm infants.

BACKGROUND: In previous studies, lower IQ scores and educational difficulties of preterm children were correlated with the reduced size of several brain areas, including the cerebellum and the hippocampus. The most plausible reason for reduction would be the reduced cell formation following premature birth. However, no data are available about the rate of postnatal cell proliferation in the different brain areas of preterms. METHODS: Cytoarchitectonics and cell proliferation were examined in the cerebellum, hippocampal formation and temporal neocortex of preterm infants who lived for several weeks or months. Cell proliferation was detected with Ki-67 immunostaining and proliferating cells were identified with vimentin as glial and with CD31 and periodic acid-Schiff (PAS) reaction as endothelial elements. RESULTS: The rate of cell formation and the width of the cytoarchitectonic layers of the cerebellum of preterm infants corresponded to that of the age-matched controls. In the hippocampal dentate gyrus, the rate of cell formation and the density of proliferating cells were slightly higher in the preterm infants than in the full-term age-matched controls. Endothelial cell proliferation and the surface area of the capillaries were larger in the dentate gyrus of preterms than in age-matched controls. CONCLUSION: Rate of cell proliferation that correlates with the postconceptual age is not reduced in preterms, therefore the reduced size of the cerebellum and hippocampal formation is unlikely to be the result of decreased cell formation.

Aging↗

PubMed2005

Umbilical vein plasma concentrations of asymmetrical dimethylarginine are increased in male but not female neonates delivered preterm: a pilot study.

BACKGROUND: Infants born term have substantially elevated plasma concentrations of the endogenous nitric oxide synthase antagonist asymmetrical dimethylarginine (ADMA) that normalize with growth. The plasma levels of ADMA in preterm newborns are unknown. SUBJECTS AND METHODS: Plasma concentrations of ADMA, symmetrical dimethylarginine (SDMA) and L-arginine were analyzed from venous umbilical cord blood samples of 19 preterm and 21 term infants by high performance liquid chromatography. RESULTS: Male preterm newborns (n=11) had higher ADMA (median [95% confidence interval (CI)]: 1.90 [1.73-2.10] micromol/l) than females born preterm (n=8; 1.57 [1.24-1.69] micromol/l; p<0.005). In term born males (n=10) and females (n=11) ADMA was significantly lower than in preterm male infants (all p<0.005), and without sex differences. SDMA and L-arginine concentrations were comparable between all groups. ADMA correlated inversely with body weight in male preterm newborns (r=-0.67; p<0.03). CONCLUSION: Male neonates delivered preterm have significantly higher umbilical cord venous plasma concentrations of ADMA compared to female neonates and infants born term. The sex difference and the time course of elevated ADMA may play a role in development and warrant further investigation.

Arginine↗