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The epidemiology of preterm labour.

Although the definition of preterm birth is birth before 37 completed weeks, the major transition in terms of needing special care occurs between 34 and 37 weeks. The Homo sapiens neonate is born much more immature than other anthropoid species, perhaps because earlier birth has evolved to avoid the large head of the human fetus becoming impacted in the small pelvis of the mother, who has become adapted to a bipedal gait. The main burden of preterm birth exists in developing countries. There are no accurate recent worldwide data, but estimates of preterm birth rates range from 5% in developed countries to 25% in developing countries. The preterm delivery rate has been relatively stable at 5-10% in developed countries for many years. The North Thames database of 517,381 pregnancies demonstrates significant ethnic variation in preterm birth rates, with higher rates in black women. This is associated with an accelerated rate of maturity in the black fetus and neonate, with correspondingly lower gestation-specific neonatal mortality rates below 38 weeks, and higher at 38 weeks of gestation and beyond. Ethnic differences can explain only a very small proportion of global preterm births. The greatest aetiological factor worldwide is infection, mainly due to malaria and HIV. In developed countries, iatrogenic delivery is responsible for almost half of the births between 28 and 35 weeks; hypertension and pre-eclampsia are the major pathologies. Other factors include multiple pregnancy, intrauterine growth restriction, maternal stress and heavy physical work.

Female↗

Impact of medically assisted fertility on preterm birth.

Preterm birth is a frequent problem in women who undergo treatment for infertility. Many factors appear to contribute to the occurrence of this complication. Infertile women seem to have a predisposition to giving birth preterm and to having low birthweight babies. These complications also occur in women with a history of infertility who achieve pregnancy without treatment and who have singleton pregnancies. Assisted reproduction patients treated with in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) have a disproportionately high occurrence of preterm births even with singleton pregnancies. Spontaneous preterm labour may be related to underlying medical conditions of the female partner, as its occurrence is not increased in subjects treated with ICSI (i.e. when the infertility problem is associated with male reproductive dysfunction in normal female partners). Multiple pregnancy is the factor most likely to be related to preterm birth in infertile women. The administration of drugs to induce ovulation either alone or combined with intrauterine insemination causes a significant increase in multiple pregnancies. The occurrence of higher order multiple pregnancy is also increased. Multiple pregnancy in women undergoing IVF or ICSI is related to the number of embryos transferred at the end of treatment. The transfer of more than two embryos in women under 35 is not associated with an increased chance of conception, while the occurrence of multiple pregnancy is significantly increased. Women over 40 may benefit from the transfer of more than two embryos, with fewer risks of multiple pregnancy. Single embryo transfer is increasingly considered a workable clinical option, particularly in young women. Hopefully, a more cautious approach to infertility management will reduce the occurrence of multiple pregnancy, spontaneous preterm labour and the high number of low birthweight infants born after treating these women.

Female↗

A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study.

OBJECTIVE: To determine whether metronidazole reduces early preterm labour in asymptomatic women with positive vaginal fetal fibronectin (fFN) in the second trimester of pregnancy. DESIGN: Randomised placebo-controlled trial. SETTING: Fourteen UK hospitals (three teaching). POPULATION: Pregnancies with at least one previous risk factor, including mid-trimester loss or preterm delivery, uterine abnormality, cervical surgery or cerclage. METHODS: Nine hundred pregnancies were screened for fFN at 24 and 27 weeks of gestation. Positive cases were randomised to a week's course of oral metronidazole or placebo. MAIN OUTCOME MEASURES: Primary outcome was delivery before 30 weeks of gestation. Secondary outcomes included delivery before 37 weeks. RESULTS: The Trial Steering Committee (TSC) recommended the study be stopped early; 21% of women receiving metronidazole (11/53) delivered before 30 weeks compared with 11% (5/46) taking placebo [risk ratio 1.9, 95% confidence interval (CI) 0.72-5.09, P = 0.18]. There were significantly more preterm deliveries (before 37 weeks) in women treated with metronidazole 33/53 (62%) versus placebo 18/46 (39%), risk ratio 1.6, 95% CI 1.05-2.4. fFN was a good predictor of early preterm birth in these asymptomatic women; positive and negative predictive values (24 weeks of gestation) for delivery by 30 weeks were 26% and 99%, respectively (positive and negative likelihood ratios 15, 0.35). CONCLUSION: Metronidazole does not reduce early preterm birth in high risk pregnant women selected by history and a positive vaginal fFN test. Preterm delivery may be increased by metronidazole therapy.

Administration, Oral↗

Pregnancy-induced hypertension is associated with lower infant mortality in preterm singletons.

OBJECTIVE: To assess the association between pregnancy-induced hypertension (PIH) and infant mortality. DESIGN: Retrospective cohort study. SETTING: Birth and infant death registration dataset of the USA. POPULATION: A total of 17,432,987 eligible, liveborn singleton births in 1995-2000. METHODS: Multivariate logistic regression was applied to evaluate the association between PIH and infant mortality, with adjustment of potential confounders. MAIN OUTCOME MEASURES: Infant death (0-364 days) and its three components: early neonatal death (0-6 days), late neonatal death (7-27 days), and postneonatal death (28-364 days). RESULTS: There was a significant reduction in infant mortality associated with PIH in early preterm infants (OR = 0.59, 95% CI: 0.56-0.63) and in late preterm infants (OR = 0.80, 95% CI: 0.73-0.87), but a significant increase in term infants (OR = 1.08, 95% CI: 1.02-1.14). Both in early preterm and late preterm births, early neonatal mortality (OR = 0.38, 95% CI: 0.34-0.42; OR = 0.68, 95% CI: 0.61-0.77) and late neonatal mortality (OR = 0.59, 95% CI: 0.50-0.70; OR = 0.76, 95% CI: 0.61-0.96) were decreased in infants born to mothers with PIH compared with those born to mothers with normal blood pressure. The PIH-associated reduction in neonatal mortality among preterm singletons was stronger in small-for-gestational-age infants than in normal growth infants and stronger in infants born to nulliparous women than in those born to multiparous women. CONCLUSIONS: PIH is associated with lower risk of infant death in preterm births but higher risk in term births.

Adult↗

Preterm birth: the value of sonographic measurement of cervical length.

Transvaginal ultrasound scanning of cervical length at approximately 20 weeks of gestation in women attending for routine antenatal care is useful for predicting the likelihood of spontaneous early preterm birth. The risk of early birth increases exponentially with decreasing cervical length in both singleton and multiple pregnancies. In such women, individualization of risk would lead to rationalisation of antenatal care, including frequency of visits, patient education in recognising and reporting symptoms of spontaneous preterm labour and timely administration of steroids. It is also possible that in women identified as being at high risk, the rate of preterm birth might be reduced by the prophylactic use of progesterone. In women presenting with threatened spontaneous preterm labour, transvaginal measurement of cervical length provides a useful distinction between those who are likely to deliver within the subsequent 7 days and those who are not. Since only 10-20% of such women are in true spontaneous preterm labour, the cervical length measurement in rational care can avoid the current practice of hospitalisation and administration of steroids and tocolytics to all. This article reviews the evidence in support of the clinical introduction of transvaginal sonography for both the prediction and management of spontaneous preterm labour.

Cervix Uteri↗

The use of high-dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome.

High-dimensional biology (HDB) refers to the simultaneous study of the genetic variants (DNA variation), transcription (messenger RNA [mRNA]), peptides and proteins, and metabolites of an organ, tissue, or an organism in health and disease. The fundamental premise is that the evolutionary complexity of biological systems renders them difficult to comprehensively understand using only a reductionist approach. Such complexity can become tractable with the use of "omics" research. This term refers to the study of entities in aggregate. The current nomenclature of "omics" sciences includes genomics for DNA variants, transcriptomics for mRNA, proteomics for proteins, and metabolomics for intermediate products of metabolism. Another discipline relevant to medicine is pharmacogenomics. The two major advances that have made HDB possible are technological breakthroughs that allow simultaneous examination of thousands of genes, transcripts, and proteins, etc., with high-throughput techniques and analytical tools to extract information. What is conventionally considered hypothesis-driven research and discovery-driven research (through "omic" methodologies) are complementary and synergistic. Here we review data which have been derived from: 1) genomics to examine predisposing factors for preterm birth; 2) transcriptomics to determine changes in mRNA in reproductive tissues associated with preterm labour and preterm prelabour rupture of membranes; 3) proteomics to identify differentially expressed proteins in amniotic fluid of women with preterm labour; and 4) metabolomics to identify the metabolic footprints of women with preterm labour likely to deliver preterm and those who will deliver at term. The complementary nature of discovery science and HDB is emphasised.

Biomarkers↗

An assessment of key aetiological factors associated with preterm birth and perinatal mortality.

The 4 main causes of preterm births in 303 women with consecutive deliveries in Flinders Medical Centre were premature rupture of the membranes (39%), spontaneous preterm labour (22%), pregnancy-induced hypertension (17%) and antepartum haemorrhage (12%). Premature rupture of the membranes occurred with equal frequency in singleton and multiple pregnancies and there was no difference in the frequency of this cause between the pregnancies with live outcomes and those with perinatal deaths. Spontaneous preterm labour was more common in multiple pregnancies (39%) than in singleton pregnancies (22%). One in 3 of the preterm births and 79% of the pregnancies with perinatal deaths occurred at less than 32 weeks' gestation. As it is unlikely that any single obstetric and social intervention will be able to reduce these causes of preterm birth research must continue to find markers to predict premature rupture of the membranes and spontaneous preterm labour.

Chi-Square Distribution↗

Is there an interaction between cervical length and cervical microbiology in the pathogenesis of preterm labour?

Transvaginal ultrasound of the cervix is increasingly used to estimate cervical length during pregnancy. Initially used to determine a possible need for cervical suture, the technique has been shown to be of value in the prediction of preterm delivery In addition, bacterial vaginosis has been shown to be associated with an increased risk of preterm delivery. We hypothesised that shortening of the cervix and potential cervical pathogens, in particular the presence of bacterial vaginosis, act synergistically in the pathogenesis of premature labour. Three hundred and sixteen women were recruited for prospective longitudinal follow-up, with both transvaginal ultrasound and cervical bacteriology performed at approximately 18 and 28 weeks gestation. A strong correlation was found between a shortened cervix and preterm delivery (p<0.02 at 18 weeks; p<0.001 at 28 weeks). Women with both a short cervix and cervical pathogens had the highest risk of preterm delivery (43%), although not significantly greater than a short cervix with normal cervical flora (31% preterm delivery). In the presence of a normal cervical length, preterm delivery rates in the presence of normal flora and potential cervical pathogens were much lower (9% and 5% respectively).

Cervix Uteri↗

Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition.

Interleukin-1 (IL-1) has been implicated in the mechanism of human parturition in the setting of infection. The purpose of this study was to determine the effect of labor (term and preterm) and microbial invasion of the amniotic cavity on amniotic fluid (AF) concentrations IL-1 alpha and IL-1 beta. AF was retrieved by transabdominal amniocentesis from the following groups of women: midtrimester genetic amniocentesis (16 to 18 wk) (N = 15), preterm labor with intact membranes (21 to 36 wk) with or without infection (N = 72), preterm premature rupture of membranes (PROM) (N = 88), and term not in labor or in active labor with or without infection (N = 58). AF was cultured for aerobic and anaerobic bacteria as well as Mycoplasmas. IL-1 was measured with a commercially available immunoassay validated for AF (sensitivity: IL-1 alpha, 157 pg/ml; IL-1 beta, 50 pg/ml). All women at midtrimester had undetectable AF IL-1 alpha and IL-1 beta. Among women in preterm labor with positive AF cultures, IL-1 alpha and IL-1 beta were detectable in the AF in 86.6% (13/15) and 100% (15/15), respectively. In contrast, all women with negative AF cultures without labor (N = 36) had undetectable AF IL-1 alpha concentrations and 52.7% (19/36) had undetectable AF IL-1 beta concentrations. Histopathological chorioamnionitis was present in 92.8% (13/14) of patients who had positive AF cultures and detectable IL-1 in the AF. IL-1 was significantly higher in patients with preterm PROM, labor, and positive AF cultures than in the other subgroups of patients with preterm PROM.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

Evidence of participation of the soluble tumor necrosis factor receptor I in the host response to intrauterine infection in preterm labor.

PROBLEM: This study was conducted to determine whether: (1) the soluble tumor necrosis factor receptor I (sTNF-rI) is present in human amniotic fluid, neonatal urine, and the feto-maternal plasma; (2) there are changes in the concentration of the sTNF-rI in amniotic fluid with gestational age; and (3) microbial invasion of the amniotic cavity (in term and preterm parturition) is associated with changes in amniotic fluid sTNF-rI concentrations. METHOD: Amniotic fluid was retrieved by amniocentesis from 185 women classified into 11 groups according to gestational age (midtrimester, preterm gestation, and term), the presence or absence of labor, spontaneous rupture of membranes and microbial invasion of the amniotic cavity. sTNF-rI was assayed with a sensitive and enzyme-linked immunosorbent assay (ELISA) validated for amniotic fluid. In addition, sTNF-rI concentrations were determined in fetal blood obtained by cordocentesis in preterm gestations (N = 24) or at the time of delivery after spontaneous labor at term (N = 10). sTNF-rI concentrations were also measured in maternal venous and cord blood and neonatal urine (n = 13). RESULTS: sTNF-rI was found to be present in all amniotic fluid samples, maternal blood and fetal blood and neonatal urine samples; sTNF-rI concentrations were higher in the midtrimester than at term (mean +/- SD: 36.2 +/- 12.2 ng/ml versus mean +/- SD: 5.56 +/- 5.72 ng/ml [P < .05]); patients with preterm labor and microbial invasion of the amniotic cavity (with intact or with ruptured membranes) had significantly higher amniotic fluid concentrations of sTNF-rI than patients without microbial invasion; in the absence of microbial invasion, parturition (both term and preterm) was not associated with changes in amniotic fluid concentrations of sTNF-rI; neonatal urine contained the highest concentrations of sTNF-rI of all biological fluids assayed including maternal and neonatal/fetal blood and amniotic fluid. CONCLUSIONS: It was concluded that sTNF-rI is a physiologic constituent of amniotic fluid, as well as of the fetal and maternal plasma; that amniotic fluid sTNF-rI concentrations decrease as a function of gestional age and increases in the concentration of the sTNF-rI are part of the host response to intrauterine infection in preterm parturition.

Adult↗

IL-15, a novel cytokine produced by human fetal membranes, is elevated in preterm labor.

PROBLEM: Interleukin (IL)-15 is a novel cytokine known to have functions similar to those of IL-2 in the cell-mediated immune response. The objectives of this study were to determine whether IL-15 levels change in labor or preterm labor and to identify the regulatory agents and the site of production of IL-15. METHOD OF STUDY: Amniochorionic membranes were cultured in an organ explant system and were stimulated with lipopolysaccharides (LPSs). Samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers for IL-15 and IL-2. The localization of mRNA and protein was accomplished by in situ hybridization and immunocytochemistry. IL-15 was measured in culture media and amniotic fluid from term and preterm gestations by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: RT-PCR indicated the expression of IL-15 mRNA in the amniochorion. In situ hybridization and immunocytochemistry documented that mRNA and peptide for IL-15 are found in amnion, chorion, and decidual cells. ELISA results indicated no significant increase of IL-15 peptides in the culture media after LPS stimulation. Maximum levels of this cytokine were seen in the amniotic fluid (AF) of women with preterm labor compared to term labor. AF levels were not higher in preterm-labor patients with proved infection compared with those without infection. RT-PCR-based detection also showed the presence of two isoforms of IL-15 mRNA known to code for two different leader peptide sequences. IL-2 mRNA expression was not observed in the fetal membranes. CONCLUSIONS: The presence of IL-15 mRNA and peptide in the amniochorion and decidua and its increased presence in the AF during preterm labor suggests a possible role for IL-15 in preterm labor. Amniochorion is also shown to possess two IL-15 isoform leader sequences, the differential expression of which may be involved in the regulation of IL-15 secretion.

Amnion↗

IFN-gamma-mediated inhibition of COX-2 expression in the placenta from term and preterm labor pregnancies.

PROBLEM: The inflammatory-anti-inflammatory cytokine network is thought to play a critical role in regulated progression and termination of pregnancy. The aim of this study was to evaluate the effects of interferon (IFN)-gamma on the expression of Cyclooxygenase (COX)-2 and production of prostaglandin E(2) (PGE(2)) in the human placenta from term and preterm labor deliveries. METHOD OF STUDY: Placental explant culture system was used. COX-2 expression was determined by complementary techniques of immunohistochemistry and Western blotting. Released IFN-gamma and PGE(2) by placental explants were measured by enzyme-linked immunosorbent assay. Signal transducer and activator of transcription 1 (STAT1) phosphorylation was evaluated by Western blotting using a specific antibody. RESULTS: IFN-gamma was poorly detected in the placenta but was significantly expressed in decidual tissues from both term and preterm pregnancies as detected by immunohistochemistry. IFN-gamma significantly inhibited COX-2 expression and PGE(2) release in cultured placental explants from term and preterm labor deliveries. This effect most likely occurred in a STAT1-dependent manner as this regulatory protein was phosphorylated in response to IFN-gamma. IFN-gamma receptor (IFN-gammaR) was expressed in normal early pregnancy placental samples. However, its expression was significantly reduced in placental samples from term and preterm deliveries. Of interest, IFN-gammaR was expressed in placentas from term and preterm labor deliveries after 24 hr in culture. CONCLUSIONS: Our data suggest that the human placenta is an important site for IFN-gamma-mediated repression of COX-2 expression and PGE2 production, implying that functional withdrawal of IFN-gamma may be involved in the onset of term or preterm labor.

Adolescent↗

Plasma ferritin concentrations in preterm infants in cord blood and during the early anaemia of prematurity.

Ferritin concentrations in cord blood were determined in 22 normal term and 32 preterm infants (birth weights 600-2000 g). Eight of the preterms were SGA infants. AGA preterm infants had significantly lower concentrations than term infants, and the SGA preterm newborn had even lower levels. Plasma ferritin in cord blood of the term and AGA preterm infants correlated positively with plasma iron and transferrin saturations, but not with the transferrin level, while plasma iron and transferrin concentrations correlated positively. In a longitudinal study, 17 AGA preterm infants (birth weights 850-1500 g) were followed during the early anaemia of prematurity. Iron was supplemented from 4 weeks of age. Plasma ferritin rose rapidly during the first days after birth, peak levels being reached at 1-4 weeks. Thereafter linear falls (semilog) occurred with similar slopes in different infants. Transferrin concentrations showed a slow progressive increase from 0-8 weeks. Plasma ferritin, after reaching the peak value, correlated negatively with weight gain. No infant had low ferritin values indicating iron deficiency during the early anaemia.

Anemia, Hypochromic↗

Comparative functional study of colostral macrophages from mothers delivering preterm and at term.

Number and function of milk macrophages (MM) from 30 healthy mothers delivering preterm (mean gestational age 33 weeks) were compared with those obtained from 92 mothers with term delivery. The average concentration of MM in colostrum did not differ in the two groups: 0.55 x 10(6)/ml (preterm) and 0.42 x 10(6)/ml (term). Preterm MM showed the same activity as term MM in all three assayed functions (phagocytosis, chemotaxis and IL-1 secretion). Phagocytic activity, and impaired migratory motility and IL-1 secretion were significantly increased both in preterm and term MM in comparison with the activity in less mature blood monocytes. Thus it appears that preterm MM are, like term MM, a fully mature tissue macrophage population and therefore we suggest that with regard to MM both preterm and term colostrum are comparable, at least in the gestational age tested.

Cell Count↗

Intact parathyroid hormone levels during pregnancy, in healthy term neonates and in hypocalcemic preterm infants.

We measured parathyroid hormone levels in pregnant and nonpregnant women and at 1, 2 and 5 days of life in healthy term neonates and in hypocalcemic preterm infants using a new immunoradiometric assay which measures only biologically active intact parathyroid hormone and by a mid-molecule parathyroid hormone radioimmunoassay. During pregnancy intact and mid-molecule parathyroid hormone levels did not show any modification and were not different from parathyroid hormone levels of nonpregnant age-matched controls. Serum calcium and phosphorus levels did not vary during each trimester of pregnancy. In cord serum intact and mid-molecule parathyroid hormone values were low in both term and preterm infants. In term neonates intact and mid-molecule parathyroid hormone levels peaked on day 1; in preterm infants intact parathyroid hormone levels peaked on day 1 while mid-molecule parathyroid hormone values peaked on day 2. Intact parathyroid hormone levels showed a more marked increase in preterm (19-fold) than in term neonates (7.5-fold) on day 1. Our data do not confirm the previously reported "physiologic" hyperparathyroidism in pregnancy. Moreover we found a normal parathyroid gland responsiveness to decreasing serum calcium levels in the first days of life in term and preterm infants. Our results suggest that measurement of intact parathyroid hormone 1-84 by immunoradiometric assay in the first days of life is a more sensitive index of parathyroid gland secretory function than the measurement of middle or carboxyl-terminal parathyroid hormone fragments allowing the detection of the dynamic changes of parathyroid hormone which occur in hypocalcemic preterm infants.

Adult↗

Plasma dopamine, norepinephrine, epinephrine and DOPAC levels in preterm infants prior to and immediately after a sleep ventilation hypercarbia test.

The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates (n = 8), and in sick preterm neonates with respiratory disorders (n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3-4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide-21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension (r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p less than 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores.

3,4-Dihydroxyphenylacetic Acid↗

Lipoproteins in preterm and small-for-gestational-age infants during the first week of life.

Plasma lipoprotein levels and composition have been determined in preterm and small-for-gestational-age (SGA) infants, and compared to full-term infants, during the first week of life. Significantly lower levels of HDL and higher levels of VLDL were found in both preterm and SGA infants in comparison to full-term healthy infants. These results suggest a low capacity to metabolize VLDL. Preterm infants showed a behaviour similar to full-term infants with regard to the changes in lipoprotein composition. Small-for-gestational-age infants showed a higher lipoprotein lipid content than preterm infants. A low ratio of cholesteryl ester to free cholesterol (CE/FC) was found in both preterm and SGA infants suggesting a reduced lecithin: cholesterol acyl transferase (LCAT) activity. In preterm infants we observed no changes in the CE/FC ratio during the first week of life, whereas in SGA infants this ratio increased after birth.

Apolipoproteins↗

Developmental delay at 12 months in children born extremely preterm.

AIM: To evaluate the feasibility and validity of a structured telephone interview to assess the development of children born extremely preterm. METHODS: The parents of 88 children born with a gestational age below 28 wk admitted to the neonatal intensive care unit (NICU) at Rigshospitalet, Copenhagen, were interviewed by telephone when their child was 1 y of age, corrected for preterm birth. A fully structured questionnaire on psychomotor function was used (Revised Prescreening Developmental Questionnaire (R-PDQ)). The parents of 30 children born at term without complications were interviewed for comparison. The interview was conducted by NICU staff. To validate the R-PDQ, parents of 22 children in the preterm group and parents of 19 children in the reference group conducted an Ages and Stages Questionnaire (ASQ) when their children had reached the age of 3-3(1/2) y. RESULTS: The R-PDQ was easy to use by staff and well accepted by parents. The mean score in the preterm group was 14.9+/-3.9 vs 17.7+/-2.7 in the term group (p<0.001). Three children had developmental scores below-2 SD. The R-PDQ score was associated with the ASQ score 2 y later. CONCLUSION: A structured questionnaire administrated by telephone is an alternative and usable tool for assessing neurodevelopmental deficit in children born extremely preterm. The mean developmental delay in the preterm group compared to the term group (about-1 SD) was close to expectations.

Child, Preschool↗