Preterm twins: what threshold of birth weight discordance heralds major adverse neonatal outcome?

OBJECTIVE: This study was undertaken to establish the optimal threshold of birth weight discordance for prediction of adverse outcome in liveborn, non-malformed preterm twins. STUDY DESIGN: We accessed a cohort of twin gestations for the period 1990 through 2000 delivered at less than 37.0 weeks' gestation. Adverse neonatal outcome was defined as stillbirth or occurrence of major morbidities. RESULTS: A total of 335 twin gestations (670 twins) were included, of which 104 (31%) experienced adverse neonatal outcome. The average birth weight discordance was 12.4% +/- 10.6% versus 19.4% +/- 14.8% in those with good versus adverse outcome (P < .001). Birth weight discordance was a significant predictor of adverse neonatal outcome that was independent of gestational age at delivery, small for gestational age, and chorionicity. Receiver operating characteristic curve analysis suggested that optimal thresholds of birth weight discordance for clinical use should take into account gestational age. CONCLUSION: Birth weight discordance is an independent predictor of adverse neonatal outcome in liveborn, non-malformed preterm twins.     

Subsequent pregnancy following labor of a very-low-birth-weight infant

During a period of 5 years (1978-1982), 55 mothers with an average age of 27.5 +/- 5.4 years, delivered 59 infants, weighing less than 1500 g. These infants had a mean birth weight of 1160.5 +/- 263 g and a mean gestational age of 28.7 +/- 2.25 weeks (range 25-32 weeks). Subsequently 47 (79.6%) survived and 12 (20.4%) died. There was a statistical difference of both mean gestational age and of mean gestational weight between survivors or infants with neonatal death. Twenty two of 29 mothers who subsequently became pregnant, gave birth to liveborn infants, who subsequently survived (four pregnancies terminated in induced abortion). Mean gestational age was 37 +/- 3 weeks (range 32-41 weeks) (P less than 0.001) and a mean birth weight was 2753.2 +/- 570 g (range 1620-3600 g) (P less than 0.001. All the 22 infants subsequently born weighed more than 1501 g, 7 (31.8%) infants weighed 1501-2500 g and 15 (68.2%) more than 2500 g. Similar data were obtained from a control group of 615 mothers (chosen at random) who delivered a normal infant at term, 202 subsequently became pregnant and 176 gave birth to a normal infant at term. Mean gestational age was 39.54 +/- 1.24 weeks (P less than 0.001) and mean birth weight was 3299.3 +/- 412 g (P less than 0.001). (In the control group 10 pregnancies terminated in induced abortions). The above data could be used in advising for future pregnancy outcome in regard to women with premature births.     

Complications of pregnancy in infertile couples: routine treatment versus assisted reproduction

Ninety pregnancies conceived by infertile couples using assisted reproductive technologies and 86 pregnancies conceived by infertile couples with routine infertility treatment were analyzed to determine the outcome of and the complications experienced during the pregnancies. Pregnancies ending after 24 weeks' gestation were evaluated for the following complications: pregnancy-induced hypertension, diabetes mellitus, preterm labor, premature rupture of membranes, placenta previa, and fetal growth retardation. A matched control group of normal fertile patients admitted to the obstetric service at Vanderbilt University Medical Center was used to compare the incidence of pregnancy complications among the groups. In the group treated by assisted reproduction, 81 pregnancies were singleton and nine were multiple gestations, whereas in the routine group, 84 were singleton and two were multiple gestations. In the group treated by assisted reproduction, 29 of 90 gestations (32%) ended before 24 weeks, compared with 18 of 86 (21%) in the routine group, a nonsignificant difference. Mean birth weight and gestational age were similar among the three groups for singleton gestations. Among multiple gestations, the mean (+/- standard error of the mean [SEM]) birth weights were 2513 +/- 115, 724 +/- 57, and 2282 +/- 132 g in the group treated by assisted reproduction, the group receiving routine methods, and the control group, respectively (P less than .001 when those treated by routine methods were compared with the other two groups). The mean (+/- SEM) gestational ages were 36 +/- 1.2, 26.5 +/- 2.0, and 35.5 +/- 1.2 weeks, respectively (P less than .01 comparing those treated by routine methods and the other two groups).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pregnancy outcome after age 50

OBJECTIVE: To evaluate pregnancy complications occurring after age 50. METHODS: We compared the pregnancy outcomes of women aged 50-64 years with those aged 45-49 years and with the general population. RESULTS: During 5 years from January 1, 1999, to June 30, 2004, 123 women aged 45 years and older gave birth. Fifty-five percent were nulliparous, 24 of 123 were aged 50-64 years, and 99 of 123 women were aged 45-49 years. All women older than age 50 conceived via in vitro fertilization with oocyte donation. For these 123 women, the overall mean gestational age at delivery was 37.6+/-2.6 weeks. The mean birth weight was 2,684+/-754 g, significantly lower than the general population, and the incidences of multifetal pregnancies, diabetes, and hypertension were high. Women aged 50 years and older were more likely to be hospitalized during pregnancy than women younger than 50 years (63% versus 22%, P<.001). Neonatal outcome was generally good. Women aged 50 years and older gave birth to significantly more low birth weight babies than those younger than age 50 years (61% versus 32%, P=.002). Gestational age and birth weight were both significantly lower for singletons and multiples in women older than age 50 years compared with those younger than age 50 years (gestational age of singletons 36.9 versus 38.4 weeks, P=.005; birth weight of singletons 2,694 versus 3,027 g, P=.019; gestational age of multiples 35.1 versus 36.4 weeks, P=.01; birth weight of multiples 1,976 versus 2,310 g, P=.038, respectively). CONCLUSION: Pregnant women aged 50-64 years have increased risks of preterm birth, low birth weight babies, diabetes mellitus, hypertension, and hospitalization. LEVEL OF EVIDENCE: II-2.     

Natural history of cervical funneling in women at high risk for spontaneous preterm birth

OBJECTIVE: To estimate the natural history of funneling in the second trimester by transvaginal ultrasonograms and whether funneling increases the risk of spontaneous birth. METHODS: Secondary analysis of a blinded, multi-center observational study of women with at least one prior spontaneous preterm birth at 16.0-31.9 weeks who subsequently carried singleton gestations. Cervical length, funneling (membrane prolapse greater than or equal to 5 mm), funnel shape, and dynamic changes were recorded at 16-18 weeks, and then every 2 weeks until 23.9 weeks. Managing obstetricians were blinded to the ultrasonography results. The primary outcome was gestational age at delivery. RESULTS: Five hundred ninety scans were performed in 183 women, of which 60 (33%) had funneling observed on at least one of the serial evaluations. These 60 women delivered at an earlier gestational age at delivery than the 123 women without funneling (31.7+/-7.9 weeks compared with 36.9+/-4.4 weeks; P<.001). In the 60 women with funneling on at least one evaluation, the progression over time of internal os cervical anatomy from a "T" to a "V" to a "U" shape was associated with earlier gestational age at delivery, whereas resolution of "V" shape funnels was associated with term delivery. Women with a shortened cervical length less than 25 mm (n=60) had a similar gestational age at birth with or without funneling (30.6+/-8.0 weeks compared with 31.9+/-6.6 weeks; P=.59). After controlling for the shortest observed cervical length, largest funnel percent was not a significant independent risk factor. CONCLUSION: The natural history of second-trimester funneling has significant variability and a significant association with earlier gestational age at delivery. As an independent finding, funneling does not add appreciably to the risk of early gestational age at delivery associated with a shortened cervical length. LEVEL OF EVIDENCE: II.     

Ocular fundus examination in premature infants.

In order to better acknowledge the ocular fundus picture in premature infants and to determine the incidence and clinical course of retinopathy of prematurity (ROP), from October 1987 to April 1989, 187 cases with a gestational age of less than 38 weeks or a birth weight of less than 2,500 g were enrolled for examination and follow-up study with indirect ophthalmoscope. One hundred and fifty cases (80.21%) were free from ROP bilaterally. Thirty-seven cases (19.79%) had ROP. Except for one case that showed unilateral regressed ROP, all were bilaterally affected. The mean birth weight and gestational age in the nonROP group were 1,824 +/- 426 g and 33.6 +/- 2.9 weeks, respectively, and in the ROP group were 1,395 +/- 490 g and 30.7 +/- 3.9 weeks, respectively. The difference for both factors between the two groups were statistically significant (p less than 0.05). Several specific fundus features were noticed in a high percentage of the nonROP group, these included a small cup to disc (C/D) ratio, pigmented ring around the disc, hypopigmented fundus and a greenish-gray color in the peripheral vascularized retina. In addition, 8.2% of this group had persistent primary vitreous remnant, and 5.6% had retinal hemorrhage. The macular development was subdivided into three stages. In both the ROP and nonROP groups, the difference of gestational age at each advancing stage was statistically significant by the Student t-test. No delay in macular development was noticed in the ROP group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Validity of postnatal assessments of gestational age in low birthweight infants from a Caribbean community.

The Dubowitz assessment of gestational maturity was compared with the best obstetric estimate of gestational age based on date of last menstrual period (LMP) or ultrasonography performed early in the pregnancy or both. This study involved 384 low birthweight infants admitted to the neonatal tertiary center in Guadeloupe, French West Indies, during the period 1986 through 1988. The Dubowitz assessment exceeded the best obstetric estimation by an average of nearly 5 days. This overestimation by the Dubowitz method was observed at every gestational age and was greatest at gestational ages of less than 35 weeks. The physical characteristics of the postnatal assessment were in closer agreement with the best obstetric estimate than the neurological characteristics. These findings concur with other investigations that indicate that the Dubowitz postnatal assessment of gestational age overestimates the gestational age interval from date of LMP in low birthweight and preterm infants.     

Preterm prelabour rupture of the membranes before 28 weeks: better than feared outcome of expectant management in Africa

OBJECTIVE: To document the prognosis after conservative management of patients with membrane rupture at gestations less than 28 weeks. STUDY DESIGN: Prospective observational study of 78 women with confirmed membrane rupture at less than 28 weeks gestation, managed conservatively. Antibiotics were given from the time of membrane rupture till delivery. Patients were delivered if clinical infection supervened, there was fetal compromise, spontaneous labour ensued or if the pregnancy continued to 34 completed weeks gestation. RESULTS: The mean gestational age at membrane rupture was 23.3+/-3.17 weeks (16.5-27.8) and the median 24 weeks. Mean latency period was 24.1+/-29.1 days (1.5-154) with a median of 12.5 days. Eight women (10%) delivered between 24 and 48 h, 25 (32%) within 7 days and 55 (70%) within 1 month. Of note is that 23 patients (30%) had latency periods of greater than 1 month. The mean gestational age at delivery was 26.7+/-3.92 weeks. Overall of the 78 women there were 81 fetuses delivered, of which 35 (43%) survived. Survival was related to latency period, birth weight and gestational age at delivery. Sixteen women (20%) developed chorioamnionitis. There was no increase in the incidence of clinical infection with increasing latency period. Compression limb abnormalities occurred in 17% of neonates and lung hypoplasia in 18%. CONCLUSION: Conservative management of patients with very preterm prelabour membrane rupture offers a survival rate of at least 40% with no serious complications in a study of 78 women.     

Rapid biometric assessment of gestational age in very low birth weight infants.

Foot length and intermamillary distance were compared to gestational age assessment using obstetrical dates, physical criteria of Ballard score and the evaluation of the anterior vascular capsule of the lens (IPM). Thirty-eight healthy and appropriate for gestational age preterm infants (30 +/- 2.4 weeks) with a birth weight of 1280 +/- 410 g were studied. Internipple distance (IM) and foot length (FL) were measured with a sliding caliper graduated in millimeters. Results were analyzed using the linear regression analysis. Obstetrical dates, physical Ballard score and IMP correlated significantly with both biometric measurements. Mean IM was 58.5 +/- 8.5 mm (range: 45 mm-89 mm) and mean FL was 60.6 +/- 7.9 mm (range: 45 mm-75 mm). The data indicate that the appropriate use of biometric parameters in the early postnatal period can be used to improve assessment of gestational age in VLBW infants.     

Impact of infertility characteristics and treatment modalities on singleton pregnancies after assisted reproduction

Obstetric and neonatal outcomes of assisted reproduction and control singletons were evaluated after taking into account treatment characteristics and infertility background. The elective single embryo transfer (eSET) group (n = 45) was compared with the compulsory single embryo transfer (cSET; n = 52), double embryo transfer (DET; n = 227) and control (n = 304) groups. Infertility-related prognostic factors for neonatal outcomes were also analysed. Data were collected with structured questionnaires at gestational week 20 and 8 weeks after delivery. Spontaneous onset of delivery was more typical of the eSET group than of cSET and DET groups (68.9 versus 52.0%, P = 0.02). Mean (+/-SD) gestation at birth (39.3 +/- 1.6 weeks) and mean birth weight (3,470 +/- 505 g) of eSET singletons were comparable with other assisted reproduction groups, but gestational duration was lower than in the eSET group than in the control group (39.9 +/- 1.4; P < 0.05). However, numbers of preterm births and low birth weight infants were similar between groups. History of induced abortion increased risk of preterm birth (OR 4.5 and 95% CI 1.2-17.1) in assisted reproduction singletons. A small though clinically unimportant difference in gestational age at birth and birth weight between assisted reproduction and control singletons was found regardless of the number of embryos transferred.     

Menotropins as a possible risk factor for premature deliveries in triplet pregnancies.

This study was undertaken in order to evaluate pregnancy outcome in three groups of triplet conceptions. Of 36 delivered triplet gestations, seven were spontaneous, 12 achieved using clomiphene citrate and 17 induced by menotropins. The mean gestational age (weeks) at delivery was 36.5 +/- 1.0 SD, for spontaneous and clomiphene citrate pregnancies it was 35.9 +/- 1.9 SD which differed significantly from that in pregnancies induced by menotropins which was 32.9 +/- 3.7 SD. Similarly, triplets born following menotropin treatment had a significantly lower gestational weight (g) of 1656 +/- 516 SD vs. 2015 +/- 198 SD and 2176 +/- 315 SD for spontaneous and clomiphene citrate gestations, respectively. It is concluded that triplets following menotropins are at an increased risk for premature delivery and low birth weight.     

Standards of Birth Weight in Twin Gestations Stratified by Placental Chorionicity

Objective: To establish fetal growth nomograms for twin gestations, categorized by placental chorionicity, and to compare them with those of published singleton and twin nomograms.Methods: Computerized data files of live births of all twins delivered between January 1990 and October 1996 at Saint Peter’s Medical Center were used. Birth weight curves corresponding to the fifth, tenth, 50th, 90th, and 95th percentiles were derived separately for twins with monochorionic and dichorionic placentation. We generated the curves by applying the method of generalized estimating equations, after adjusting for the potential intracluster correlation due to twinning. The curves were then smoothed on the basis of nonparametric restricted cubic splines to derive (smoothed) birth weight percentiles. We then compared our twin birth weight nomogram to six previously published singleton and two twin nomograms published previously for predicting small for gestational age infants (defined as birth weight below the tenth percentile).Results: Among 1302 twin fetuses, 272 (21%) were monochorionic. Twins from monochorionic gestations weighed, on average, 66.1 g (standard deviation 28.4 g, P = .02) less than twins from dichorionic gestations after correcting for gestational age. Twin curves based on parity (nulliparity versus multiparity) were not different from each other. Analyses indicate that all previously published singleton nomograms approximate twin growth reasonably well between 32 and 34 weeks, but they underestimate twin growth at earlier gestational ages (between 25 and 32 weeks) and overestimate twin growth beyond 34 weeks’ gestation. Similarly, a comparison of previously published twin nomograms with those of ours indicates that the growth standards in our population were similar to those in other published twin nomograms.Conclusion: We recommend that future epidemiologic and clinical studies use twin nomograms to identify growth-restricted twin fetuses. Moreover, because fetal growth is influenced by placental chorionicity, we recommend that fetal growth assessment in twin gestations consider placental chorionicity, whenever the information is available.     

Triplet gestation outcomes in relation to maternal prepregnancy body mass index and weight gain.

OBJECTIVE: To study prepregnancy maternal body mass index (BMI) and overall maternal weight gain in triplet gestations in relation to maternal and newborn outcomes. STUDY DESIGN: This was a retrospective study of birth certificate data of all live-born triplet gestations occurring between 1999 and 2003 in an eight-county region in New York. An analysis of computerized birth certificate data for variables related to pregnancy and newborn outcomes was conducted, looking at neonatal birth weight, neonatal gestational age, and the occurrence of the maternal pregnancy complications of gestational diabetes, gestational hypertension, and preeclampsia. RESULTS: In 56 triplet gestations studied, the prepregnancy BMI was not associated with mean newborn birth weights and gestational age at delivery. The total maternal weight gain was associated with increasing mean birth weight and higher gestational age at delivery. Pregnancy complications in triplet pregnancies of gestational diabetes and gestational hypertension were associated with prepregnancy BMI, but not maternal weight gain. CONCLUSION: For triplet gestations, a normal prepregnancy BMI and a total gestational weight gain of at least 15.9 - 20.5 kg (35 - 45 lb) are associated with fewer pregnancy complications.     

Multifetal pregnancy reductions of triplets to twins: comparison with nonreduced triplets and twins.

OBJECTIVE: Multifetal pregnancy reduction has been shown to improve survival rates in high-order multifetal pregnancies (>/=4). There is, however, some controversy as to whether multifetal pregnancy reduction improves pregnancy outcomes of triplets reduced to twins. The purpose of this study was to evaluate this issue by comparing outcomes of triplet gestations undergoing reduction to twins with outcomes of nonreduced twin gestations and expectantly managed triplet gestations. STUDY DESIGN: The study included 143 triplet pregnancies that underwent reduction to twins over a 10-year period at a single center. These were compared with 12 nonreduced triplet pregnancies from the Wayne State University Perinatal Database and with 2 groups of twin pregnancies: 605 from the Wayne State University Perinatal Database and 207 from the Quest Diagnostics Database. RESULTS: The miscarriage rate for expectantly managed triplets was 25%, compared with 6.2% for triplets reduced to twins. This rate was similar to the rates for both groups of nonreduced twins: 5.8% (Quest) and 6.3% (Wayne State University). Severe prematurity occurred in 25% of nonreduced triplets compared with 4. 9% of twins after reduction. This rate was also similar to that of nonreduced twins: 7.7% (Quest) and 8.4% (Wayne State University). The mean gestational age at delivery for expectantly managed triplets (32.9 +/- 4.7 weeks) was significantly shorter than for triplets reduced to twins (35.6 +/- 3.1 weeks). By comparison, nonreduced twins had a mean gestational age at delivery of 35.8 +/- 3.9 weeks for Quest and 34.4 +/- 3.6 weeks for Wayne State University. Mean birth weights were significantly lower in expectantly managed triplets as compared with triplets undergoing reduction to twins (1636 +/- 645 g vs 2381 +/- 602 g, respectively). Nonreduced twins had a mean birth weight of 2254 +/- 653 g for Quest and 2123 +/- 634 g for Wayne State University. Pregnancy loss rates, mean length of gestation, and mean birth weight did not vary significantly between triplets who underwent reduction to twins and nonreduced twins. CONCLUSIONS: Reduction of triplets to twins significantly reduces the risk for prematurity and low birth weight and may also be associated with a reduction in overall pregnancy loss. This suggests that multifetal pregnancy reduction of triplets to twins is a medically justifiable procedure not only from an actuarial viewpoint but also from the ethical perspective of supporting patients' autonomy and respect for patients' individual circumstances.     

Preterm birth unrelated to maternal height in Asian women with singleton gestations.

OBJECTIVE: To determine whether maternal height has a significant effect on the length of gestation or the incidence of preterm birth in Asian women with singleton gestations. METHODS: We retrospectively studied a cohort of consecutive adult Asian women with singleton gestations who delivered in a 2-year period, to determine the relationship between maternal height, expressed in quartiles, and the mean gestational age and incidence of preterm birth. RESULTS: Of the 9819 deliveries during that period, 449 were excluded from analysis because of multiple gestation, maternal age less than 20 years, or incomplete data because of no antenatal care in our hospital. The 25th, 50th, and 75th percentile values of maternal height were 152, 156, and 160 cm, respectively. Significant differences were found in the maternal age, weight and body mass index (BMI), birth weight, and birth weight as a percentage of maternal weight, among the four quartiles, but the trend for age, BMI, and birth weight percentage was opposite to that of maternal weight and birth weight. However, there was no significant difference in the mean gestational age or incidence of preterm birth at less than 28, 28-31, or 32-36 weeks' gestation. There was no difference in the incidence of pregnancies beyond 41 weeks' gestation. CONCLUSION: Maternal stature does not have a significant influence on the mean gestational age or incidence of preterm birth in adult Asian women with singleton gestations.     

Relationship between cortisol levels in umbilical cord plasma and development of the respiratory distress syndrome in premature newborn infants.

The aim of this study was to determine whether there is a decrease in fetal cortisol levels associated with the respiratory distress syndrome (RDS). Eighteen newborn infants of less than 37 weeks' gestation who developed moderate to severe forms of RDS did have a significantly lower (P less than 0.02) mean cord plasma cortisol concentration at birth than that observed in 67 unaffected infants of similar gestational age; mean values +/- standard errors were 3.36 +/- 0.42 and 5.58 +/- 0.43 mug per 100 ml, respectively. However, whether or not RDS developed in neonates appeared to depend more upon the degree of prematurity (with a 71.5% incidence in gestations of less than 32 weeks compared to 17.1% in those of 32 to less than 37 weeks) than upon cortisol levels at delivery. Bood cortisol levels in the first days of life of four infants with RDS were considerably increased in comparison to those at birth. Mean cord plasma cortisol concentrations increased with duration of pregnancy, with the previously observed value for term infants (of 37 or more weeks) being approximately twice that for infants of less than 32 weeks' gestation. These findings appear to justify carefully controlled studied with antepartum glucocorticoid administration with the aim of reducing the incidence of RDS in premature newborn infants.     

Effects of placental chorionicity on outcome in twin pregnancies. A cohort study.

OBJECTIVE: To examine the effects of the chorionicity of the placenta on infant outcome at 1 year of age in twin pregnancies. STUDY DESIGN: Cohort study and retrospective review of the medical records of 44 monochorionic (MC) and 164 dichorionic (DC) twin gestations that had been followed at our institution since < 20 weeks' gestation. Physical and neurologic status was assessed at 1 year of corrected age in infants born to these 208 women. RESULTS: Adverse infant outcomes, such as death, cerebral palsy and mental retardation, occurred in 9 (10%) of 88 MC infants (4 deaths and 5 disabled infants) as compared with 12 (3.7%) of 328 DC infants (6 deaths and 6 disabled infants) (P < .05). Although delivery occurred one week earlier in MC than in DC twins (34.7 +/- 2.8 vs. 35.7 +/- 2.3 weeks, P < .01), there was no significant difference in gestational age at birth or birth weight between the 9 MC and 12 DC infants with adverse outcomes. A presumptive antenatal diagnosis of twin-twin transfusion syndrome (TTTS) was made in 14 (32%) of the 44 MC twin gestations. TTTS was considered to be responsible for adverse outcome in 7 MC infants. All 9 MC infants with adverse outcomes and 4 (33%) of 12 DC infants with adverse outcomes belonged to pairs that had weight discordance > or = 25% (P < .01). CONCLUSION: MC twins had an increased risk of adverse outcomes as compared with DC twins, mainly because of TTTS. In both MC and DC twins, a birth weight discordance > or = 25% was associated with adverse infant outcomes. The number of infants with disabilities at 1 year of age was equal to the number of deaths.     

Outpatient triplet management: a contemporary review

The antepartum management of 198 women who were delivered of triplets between 1985 and 1988 is reviewed. Women were managed with the assistance of ambulatory perinatal nursing to provide outpatient surveillance. Modified bed rest, prophylactic tocolysis, and betamethasone were liberally used and patients were hospitalized only when obstetrically indicated. The most common antepartum complication was preterm labor (66.2%) and the success of therapy with tocolytic agents is described. The mean gestational age and birth weight at delivery were 33.6 +/- 3 weeks (mean +/- SD) and 1871 +/- 555 gm, respectively. Comparison of the gestational age distribution at delivery with previous reviews demonstrates fewer deliveries less than 29 weeks' gestation and significantly more deliveries between 32 and 37 weeks' gestation. Cesarean delivery occurred in 94% of the triplets, which eliminated birth order as a factor that affects survival. The corrected perinatal survival rate was 95% in this contemporary review of outpatient triplet management and represents a major improvement in the expected outcome for triplets.     

Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis

OBJECTIVE: Neonatal cerebral white matter injury represents a major precursor for neurological impairment and cerebral palsy. Our objective was to identify risk factors associated with its development. STUDY DESIGN: This retrospective case-control study of all births between 23 and 34 weeks gestation at a single university hospital between May 1994 and September 2001 identified 150 cases with white matter injury characterized by periventricular leukomalacia or ventricular dilatation from white matter atrophy that were chromosomally normal and did not have other congenital anomalies. Cases were matched to controls without brain injury by the next delivery within 7 days of their gestational age. RESULTS: There were small differences between controls and cases in gestational age (27.5 +/- 2.7, 27.4 +/- 2.6 weeks, P = .01) and birth weight (1053 +/- 402, 966 +/- 285 g, P = .002) that were statistically but not clinically significant. There was no difference in the percentage of controls and cases delivered by cesarean (45%, 49%, P = .64). There were no differences between controls and cases in umbilical arterial pH (7.27 +/- 0.11, 7.25 +/- 0.15, P = .19), base excess (-2.1 +/- 2.7, -3.0 +/- 4.1 mmol/L, P = .28), pH less than 7.0 (2/122 [2%], 3/107 [3%], P = 1.0), or base excess less than -12 mmol/L (4/121 [3%], 6/106 [6%], P = .75). The cases had a significant increase in positive blood (19%, 29%, P = .036), cerebrospinal fluid (6%, 17%, P = .002), and tracheal (9%, 22%, P = .003) cultures during the neonatal period. Conditional logistic regression showed a significant association among multiple gestations ( P = .02), intraventricular hemorrhage ( P < .001), and positive tracheal cultures ( P = .02) with cerebral white matter injury. CONCLUSION: Culture-positive infection was associated with an increased risk of cerebral white matter injury in preterm neonates. Intrapartum hypoxia-ischemia as manifested by metabolic acidosis was rarely associated with white matter injury and was not different from the incidence in premature neonates without injury.