Abstract: Background Very preterm infants are at high risk for adverse neurodevelopmental outcomes. Magnetic resonance imaging (MRI) has been proposed as a means of predicting neurodevelopmental outcomes in this population. Methods We studied 167 very preterm infants (gestational age at birth, 30 weeks or less) to assess the associations between qualitatively defined white-matter and gray-matter abnormalities on MRI at term equivalent (gestational age of 40 weeks) and the risks of severe cognitive delay, severe psychomotor delay, cerebral palsy, and neurosensory (hearing or visual) impairment at 2 years of age (corrected for prematurity). Results At two years of age, 17 percent of infants had severe cognitive delay, 10 percent had severe psychomotor delay, 10 percent had cerebral palsy, and 11 percent had neurosensory impairment. Moderate-to-severe cerebral white-matter abnormalities present in 21 percent of infants at term equivalent were predictive of the following adverse outcomes at two years of age: cognitive ...

Abstract: Background Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain. Methods We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age. Results Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia ...

Abstract: Context Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants and maternal depression both alter neonatal health, and distinguishing the effects of each influence remains challenging. Objective To determine whether exposure to SSRIs and depression differs from exposure to maternal depression alone. Design Using population health data, records of neonatal birth outcomes were linked to records of maternal health and prenatal maternal prescriptions for SSRIs. Setting Population of British Columbia, Canada. Participants Mothers and their infants, representing all live births during a 39-month period (N = 119 547) (1998-2001). Main Outcome Measures Outcomes from infants of depressed mothers treated with SSRIs (SE-D) were compared with outcomes from infants of depressed mothers not treated with medication (DE) and nonexposed controls. To control for maternal mental illness severity, propensity score matching was used to identify a comparison group of DE mothers who were similar to the SE-D mothers in characteristics in the year preceding and during pregnancy. Results Fourteen percent of mothers were diagnosed as having depression during their pregnancy, and the incidence of prenatal SSRI exposure increased from 2.3% to 5.0% during a 39-month period. Birth weight and gestational age for SE-D infants were significantly less than for DE infants, as was the proportion of infants born at less than 37 weeks (95% confidence interval [CI], −1 to −64, −0.25 to −0.45, and −0.009 to −0.04, respectively), although differences in the incidence of birth weight less than the 10th percentile for gestational age were not significant. An increased proportion of SE-D infants had neonatal respiratory distress (13.9% vs 7.8%), jaundice (9.4% vs 7.5%), and feeding problems (3.9% vs 2.4%) compared with DE infants (95% CI of difference, 0.042-0.079, 0.003-0.334, and 0.005-0.025, respectively). When outcomes were compared between SE-D and propensity score–matched DE neonates, SE-D was associated with increased incidence of birth weight below the 10th percentile and rates of respiratory distress. Conclusion With linked population health data and propensity score matching, prenatal SE-D exposure was associated with an increased risk of low birth weight and respiratory distress, even when maternal illness severity was accounted for.

Abstract: Background Maternal periodontal disease has been associated with an increased risk of preterm birth and low birth weight. We studied the effect of nonsurgical periodontal treatment on preterm birth. Methods We randomly assigned women between 13 and 17 weeks of gestation to undergo scaling and root planing either before 21 weeks (413 patients in the treatment group) or after delivery (410 patients in the control group). Patients in the treatment group also underwent monthly tooth polishing and received instruction in oral hygiene. The gestational age at the end of pregnancy was the prespecified primary outcome. Secondary outcomes were birth weight and the proportion of infants who were small for gestational age. Results In the follow-up analysis, preterm birth (before 37 weeks of gestation) occurred in 49 of 407 women (12.0%) in the treatment group (resulting in 44 live births) and in 52 of 405 women (12.8%) in the control group (resulting in 38 live births). Although periodontal treatment improved periodo...

Abstract: Background Bronchopulmonary dysplasia in premature infants is associated with prolonged hospitalization, as well as abnormal pulmonary and neurodevelopmental outcome. In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial. Methods We conducted a randomized, stratified, double-blind, placebo-controlled trial of inhaled nitric oxide at 21 centers involving infants with a birth weight of 1250 g or less who required ventilatory support between 7 and 21 days of age. Treated infants received decreasing concentrations of nitric oxide, beginning at 20 ppm, for a minimum of 24 days. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Results Among 294 infants receiving nitric oxide and 288 receiving placebo birth weight (766 g and 759 g, respectively), gestational age (26 weeks in both groups), and other characteristics were sim...

Abstract: OBJECTIVE. Ductus arteriosus (DA) closure occurs within 96 hours in >95% of neonates >1500 g in birth weight (BW). The prevalence and postnatal age of spontaneous ductal closure in neonates ≤1000 g in BW (extremely low birth weight [ELBW] neonates) remain unclear, as does the incidence of failure to close with indomethacin. Therefore, we prospectively examined the prevalence, postnatal age, and clinical variables associated with spontaneous DA closure, occurrence of persistent patent DA, and indomethacin failure in ELBW neonates. METHODS. Neonates delivered at Parkland Memorial Hospital from February 2001 through December 2003 were studied. Those with congenital heart defects or death RESULTS. We studied 122 neonates with BW of 794 ± 118 (SD) g and estimated gestational age (EGA) of 26 ± 2 weeks. Spontaneous permanent DA closure occurred in 42 (34%) neonates at 4.3 ± 2 days postnatally, with 100% closure by 8 days. These neonates were more mature, less likely to have received antenatal steroids or have hyaline membrane disease (HMD; 52% vs 79%), and more likely to be growth restricted (31% vs 5%) and delivered of hypertensive women. Using regression analysis, EGA and absence of antenatal steroids and HMD predicted ductal closure. Ten (8%) neonates with early DA closure reopened and required medical/surgical closure. Eighty neonates had persistent patent DA; 7 were surgically ligated, and 5 remained asymptomatic, with 4 of 5 closing after 10 days postnatally. Sixty-eight (85%) received indomethacin at 6.2 ± 4 days postnatally; 41% failed therapy and had no distinguishing characteristics. CONCLUSIONS. Spontaneous permanent DA closure occurs in >34% of ELBW neonates and is predicted by variables related to maturation, for example, EGA and an absence of HMD, whereas indomethacin failure could not be predicated.

Abstract: Concern exists that a constellation of negative maternal emotions during pregnancy generates persistent negative consequences for child development. Maternal reports of anxiety, pregnancy-specific and nonspecific stress, and depressive symptoms were collected during mid-pregnancy and at 6 weeks and 24 months after birth in a sample of healthy women with low risk pregnancies. Developmental assessment and cardiac vagal tone monitoring were administered to 94 children at age 2. Higher levels of prenatal anxiety, nonspecific stress, and depressive symptoms were associated with more advanced motor development in children after postnatal control for each psychological measure; anxiety and depression were also significantly and positively associated with mental development. Mild to moderate levels of psychological distress may enhance fetal maturation in healthy populations.

Abstract: OBJECTIVE. To estimate the prevalence of cerebral palsy at 2 years of age among children born very preterm, according to gestational age, infant gender, plurality, and neonatal cranial ultrasound abnormalities. METHODS. All infants born between 22 and 32 weeks of gestation in 9 regions of France in 1997 were included in this prospective, population-based, cohort study. The main outcome measure was cerebral palsy prevalence at 2 years. Of the 2364 survivors eligible for follow-up evaluation, 1954 (83%) were assessed at 2 years of age. RESULTS. Among the 1954 children assessed at 2 years, 8.2% had cerebral palsy. Bilateral spastic cerebral palsy, hemiplegia, and monoplegia accounted for 72%, 9%, and 10% of cases, respectively. Fifty percent of the children with cerebral palsy walked independently at the age of 2, 31% were unable to walk but could sit independently, and 19% could not sit (unable to maintain head and trunk control). The prevalence of cerebral palsy was 20% at 24 to 26 weeks of gestation, compared with 4% at 32 weeks. On the basis of ultrasound findings in the neonatal period, we found that 17% of children with isolated grade III intraventricular hemorrhage and 25% of children with white matter damage (ie, ventricular dilation, persistent echodensities, or cystic periventricular leukomalacia) had cerebral palsy, compared with 4% of children with normal ultrasound scans. CONCLUSIONS. Despite recent improvements in survival rates, cerebral palsy remains highly prevalent among very preterm children. Severe cranial ultrasound abnormalities predict motor disability strongly, but one third of infants with cerebral palsy had no ultrasound abnormalities.

Abstract: Objective This article investigates the effects of antenatal depression and anxiety on spontaneous preterm birth resulting either from preterm labor or preterm premature rupture of membranes. Methods We conducted a prospective cohort study of 681 women with singleton pregnancies consecutively recruited between 20 and 28 weeks of gestation in the Obstetrics Department of the French University Hospital of Caen. Most were of European ethnic origin and received early and regular antenatal care. The assessment of gestational age was based on ultrasound examination (occurring before 13 weeks of gestation for 94.9% of the women). Depression and anxiety were assessed using self-administered questionnaires: the Edinburgh Postnatal Depression Scale and the Spielberger State-Trait Anxiety Inventory. Logistic regression analysis, controlling for sociodemographic factors (e.g., maternal age, occupation) and obstetric factors (e.g., previous preterm birth, cervical or vaginal infection), provided adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results Spontaneous preterm birth occurred in 31 women (4.8%). The rate of spontaneous preterm birth was significantly higher among women with high depression scores (9.7%) as opposed to other women (4.0%) even after adjustment for potential confounding factors (adjusted OR = 3.3, 95% CI = 1.2-9.2, p = .020). Anxiety was not significantly associated with the outcome. There were no significant interaction effects between psychological and biomedical factors. Conclusions These findings provide evidence that antenatal depression is significantly associated with spontaneous preterm birth in a population of European women receiving early and regular care.

Abstract: Maternal stress is commonly cited as an important risk factor for spontaneous abortion. For humans, however, there is little physiological evidence linking miscarriage to stress. This lack of evidence may be attributable to a paucity of research on maternal stress during the earliest gestational stages. Most human studies have focused on “clinical” pregnancy (>6 weeks after the last menstrual period). The majority of miscarriages, however, occur earlier, within the first 3 weeks after conception (≈5 weeks after the last menstrual period). Studies focused on clinical pregnancy thus miss the most critical period for pregnancy continuance. We examined the association between miscarriage and levels of maternal urinary cortisol during the first 3 weeks after conception. Pregnancies characterized by increased maternal cortisol during this period (within participant analyses) were more likely to result in spontaneous abortion (P < 0.05). This evidence links increased levels in this stress marker with a higher risk of early pregnancy loss in humans.

Abstract: Background The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain Methods We performed a multicenter, randomized trial involving 793 newborns who were 34 weeks of gestational age or less and had respiratory failure requiring mechanical ventilation Newborns were randomly assigned to receive either inhaled nitric oxide (5 ppm) or placebo gas for 21 days or until extubation, with stratification according to birth weight (500 to 749 g, 750 to 999 g, or 1000 to 1250 g) The primary efficacy outcome was a composite of death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age Secondary safety outcomes included severe intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly Results Overall, there was no significant difference in the incidence of death or bronchopulmonary dysplasia between patients receiving inhaled nitric oxide and those receiving placebo (716 percent vs 753 percent,

Abstract: OBJECTIVE. We sought to examine, in a large cohort of infants within a definable population of live births, the incidence, risk factors, treatments, complications, and outcomes of meconium aspiration syndrome (MAS). DESIGN. Data were gathered on all of the infants in Australia and New Zealand who were intubated and mechanically ventilated with a primary diagnosis of MAS (MASINT) between 1995 and 2002, inclusive. Information on all of the live births during the same time period was obtained from perinatal data registries. RESULTS. MASINT occurred in 1061 of 2490862 live births (0.43 of 1000), with a decrease in incidence from 1995 to 2002. A higher risk of MASINT was noted at advanced gestation, with 34% of cases born beyond 40 weeks, compared with 16% of infants without MAS. Fetal distress requiring obstetric intervention was noted in 51% of cases, and 42% were delivered by cesarean section. There was a striking association between low 5-minute Apgar score and MASINT. In addition, risk of MASINT was higher where maternal ethnicity was Pacific Islander or indigenous Australian and was also increased after planned home birth. Uptake of exogenous surfactant, high-frequency ventilation, and inhaled nitric oxide increased considerably during the study period, with >50% of infants receiving ≥1 of these therapies by 2002. Risk of air leak was 9.6% overall, with an apparent reduction to 5.3% in 2001–2002. The duration of intubation remained constant throughout the study period (median: 3 days), whereas duration of oxygen therapy and length of hospital stay increased. Death related to MAS occurred in 24 infants (2.5% of the MASINT cohort; 0.96 per 100000 live births). CONCLUSIONS. The incidence of MASINT in the developed world is low and seems to be decreasing. Risk of MASINT is significantly greater in the presence of fetal distress and low Apgar score, as well as Pacific Islander and indigenous Australian ethnicity. The increased use of innovative respiratory supports has not altered the duration of mechanical ventilation.

Abstract: OBJECTIVE. Postnatal corticosteroid therapy is controversial. The aim of this study was to determine the short-term effects of low-dose dexamethasone treatment among chronically ventilator-dependent neonates. METHODS. Very preterm (gestational age: RESULTS. Seventy infants were recruited from 11 centers, at a median age of 23 days. More infants were extubated successfully by 10 days of treatment in the dexamethasone group (60%, 21 of 35 patients) than in the control group (12%, 4 of 34 patients) (odds ratio [OR]: 11.2; 95% confidence interval [CI]: 3.2–39.0). Ventilator and oxygen requirements improved substantially, and the duration of intubation was shorter. There was little evidence for a reduction in either the mortality rate (dexamethasone group: 11%; control group: 20%; OR: 0.52; 95% CI: 0.14–1.95) or the rate of oxygen dependence at 36 weeks (dexamethasone group: 85%; control group: 91%; OR: 0.58; 95% CI: 0.13–2.66). There were no obvious effects of low-dose dexamethasone on blood glucose concentrations, blood pressure, or other complications. No infant experienced intestinal perforation. CONCLUSIONS. Low-dose dexamethasone treatment after the first 1 week of life clearly facilitates extubation and shortens the duration of intubation among ventilator-dependent, very preterm/extremely low birth weight infants, without any obvious short-term complications. Combined with recent evidence that infants at very high risk of bronchopulmonary dysplasia may benefit in the long term, our study reopens debate regarding the role of low-dose, late postnatal, corticosteroid therapy.

Abstract: Objectives Intrauterine growth restriction is a common clinical problem, but the underlying hemodynamic changes are not well known. Our aim was to determine the normal distribution of fetal cardiac output to the placenta during the second half of pregnancy, and to assess the changes imposed by growth restriction with various degrees of placental compromise. Methods A cross-sectional study of 212 low-risk pregnancies with a gestational age of 18–41 weeks constituted the reference population. A second group of 64 pregnancies with an estimated fetal weight ⩽ 2.5th percentile constituted the study group. Ultrasound measurements of inner diameters and velocities at the fetal left and right ventricular outlets and intra-abdominal umbilical vein were used to determine combined left and right cardiac output (CCO) and the fraction distributed to the placenta. Placental compromise was graded according to umbilical artery waveform: pulsatility index normal, > 97.5th percentile, or absent/reversed end-diastolic velocity. Regression analysis and Z-score (SD-score) statistics were used to establish normal ranges and to compare groups. Results During gestational weeks 18–41 the normal CCO/kg was on average 400 mL/min/kg and the fraction directed to the placenta was on average 32%, while after 32 weeks it was 21%. In intrauterine growth restriction the CCO/kg was not significantly different, but the fraction to the placenta was lower (P < 0.001). This effect was more pronounced in severe placental compromise (P < 0.001). Conclusions Normally, one third of the fetal CCO is distributed to the placenta in most of the second half of pregnancy, and one fifth near term. In placental compromise this fraction is reduced while CCO/kg is maintained at normal levels, signifying an increased recirculation of umbilical blood in the fetal body. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Abstract: OBJECTIVE. Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development, Environment and Lifestyle study. DESIGN/METHOD. The Infant Development, Environment and Lifestyle study screened 13808 subjects at 4 clinical centers: 1618 were eligible and consented, among which 84 were methamphetamine exposed, and 1534 were unexposed. Those who were methamphetamine exposed were identified by self-report and/or gas chromatography-mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Those who were unexposed denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, or marijuana use, but excluded use of opiates, LSD, PCP or cocaine only. Neonatal parameters included birth weight and gestational age in weeks. One-way analysis of variance and linear-regression analyses were conducted on birth weight by exposure. The relationship of methamphetamine exposure and the incidence of small for gestational age was analyzed using multivariate logistic-regression analyses. RESULTS. The methamphetamine exposed group was 3.5 times more likely to be small for gestational age than the unexposed group. Mothers who used tobacco during pregnancy were nearly 2 times more likely to have small-for-gestational-age infants. In addition, less maternal weight gain during pregnancy was more likely to result in a small-for-gestational-age infant. Birthweight in the methamphetamine exposed group was lower than the unexposed group. CONCLUSIONS. These findings suggest that prenatal methamphetamine use is associated with fetal growth restriction after adjusting for covariates. Continued follow-up will determine if these infants are at increased risk for growth abnormalities in the future.

Abstract: Objective.To identify prenatal and perinatal risk factors for clinically severe(stage 3 or 4)retinopathy of prematurity(ROP).Methods.Data were collected prospectively as part of the ongoing Australian and New Zealand Neonatal Network audit of high-risk infants(birth weight of 1500 g or gestational age GA of 32 weeks)admitted to a level III neonatal unit in Australia or New Zealand.Prenatal and perinatal factors to 1 minute of age were examined for the subset of infants with GA of 29 weeks who survived to 36 weeks' postmenstrual age and were examined for ROP(n=2105).The factors significantly associated with stage 3 or 4 ROP were entered into amultivariate logistic regression model.Results.Two-hundred three infants(9.6%)had stage 3 or more ROP.Prematurity was the dominant risk factor,with infants with GA of 25 weeks having 20 times greater odds of severe ROP than infants with GA of 28 weeks.Birth weight for GA also had a “ dose-response” effect;the more growthrestricted infants had greater risk,with infants below the 3rd percentile of weight for GA having 4 times greater odds of severe ROP than those between the 25th and 75th percentiles.Male gender was also a significant risk factor(odds ratio:1.73;95% confidence interval:1.25-2.40).Conclusions.These data,for a large,essentially population-based cohort,suggest that factors related to the degree of immaturity,intrauterine growth restriction,and male gender contribute to severe ROP.

Abstract: OBJECTIVE. The objective of this study was to document pulse oximeter saturation levels achieved in the first 4 weeks of life in infants who were born at METHODS. Infants who were RESULTS. Fourteen centers from 3 countries enrolled 84 infants with mean ± SD birth weight of 863 ± 208 g and gestational age of 26 ± 1.4 weeks. Oxygen saturation policy limits ranged between 83% and 92% for lower limits and 92% and 98% for upper limits. For infants who received respiratory support, median pulse oximeter saturation level achieved was 95%. Center-specific medial levels were within the intended range at 12 centers. Centers maintained infants within their intended range 16% to 64% of the time but were above range 20% to 73% of the time. In hierarchical modeling, wider target ranges, higher target range upper limits, presence of a policy of setting oximeter alarms close to the target range limits, and lower gestational age were associated with improved target range compliance. CONCLUSIONS. Success with maintaining the intended pulse oximeter saturation range varied substantially among centers, among patients within centers, and for individual patients over time. Most noncompliance was above the intended range. Methods for improving compliance and the effect of improved compliance on neonatal outcomes require additional research.