Neonatal outcomes of small for gestational age preterm infants in Canada

To compare the effect of small for gestational age (SGA) on mortality, major morbidity and resource utilization among singleton very preterm infants (<33 weeks gestation) admitted to neonatal intensive care units (NICUs) across Canada. Infants admitted to participating NICUs from 2003 to 2008 were divided into SGA (defined as birth weight <10th percentile for gestational age and sex) and non-small gestational age (non-SGA) groups. The risk-adjusted effects of SGA on neonatal outcomes and resource utilization were examined using multivariable analyses. SGA infants (n = 1249 from a cohort of 11,909) had a higher odds of mortality (adjusted odds ratio [AOR] 2.46; 95% confidence interval [CI], 1.93-3.14), necrotizing enterocolitis (AOR 1.57; 95% CI, 1.22-2.03), bronchopulmonary dysplasia (AOR 1.78; 95% CI, 1.48-2.13), and severe retinopathy of prematurity (AOR 2.34; 95% CI, 1.71-3.19). These infants also had lower odds of survival free of major morbidity (AOR 0.50; 95% CI, 0.43-0.58) and respiratory distress syndrome (AOR 0.79; 95% CI, 0.68-0.93). In addition, SGA infants had a more prolonged stay in the NICU, and longer use of ventilation continuous positive airway pressure, and supplemental oxygen (p < 0.01 for all). SGA infants had a higher risk of mortality, major morbidities, and higher resource utilization compared with non-SGA infants.     

Transient bilirubin encephalopathy and apnea of prematurity in 28 to 32 weeks gestational age infants.

OBJECTIVE: Apnea of prematurity (AoP) is, in part, a reflection of brainstem-mediated respiratory control system maturation. We previously demonstrated changes in brainstem function in relation to hyperbilirubinemia (bilirubin encephalopathy, (BE)) as evaluated by auditory brainstem evoked responses (ABR) in infants 28 to 32 weeks gestational age (GA). We hypothesized that in this population, as bilirubin increases and causes auditory brainstem dysfunction, respiratory control system may also be adversely affected leading to increased frequency of AoP. STUDY DESIGN: We studied 100, 28 to 32 weeks GA infants and identified 66 with normal and 34 with abnormal ABR progression in temporal relation to hyperbilirubinemia (BE). The abnormal ABR progression was associated with elevated bilirubin, specifically elevated unbound bilirubin levels. A blinded, retrospective chart review quantified the amount of weekly apnea and bradycardia events during the hospital stay, total duration of methylxanthine treatment, total duration of mechanical ventilation, CPAP, and/or nasal cannula, and risk factors for apnea (sepsis, IVH grade >II, asphyxia). Since mechanical ventilation confounds the identification of apnea, infants requiring mechanical ventilation were excluded from further review (n = 60; 21 with BE and 39 with normal ABR progression). Data from the remaining 40 infants were analyzed. Student's t-test was used to analyze continuous variables if the distribution was normal otherwise Wilcoxon-ranked-sum test was used. chi(2) was used to analyze nominal variables. A p < or =0.05 was considered significant. RESULTS: There was no difference in risk factors between infants with and without BE. BE was identified on day 3 (median; range 1 to 6 days). Patients with BE had significantly more apneic events (15 vs 2, p = 0.0009), bradycardic events (14 vs 1, p = 0.02), and required more prolonged treatment with CPAP (2.2 vs 0.5 days, p = 0.007), nasal cannula (6.6 vs 2.2 days, p = 0.02), and methylxanthines (9.5 vs. 1.9 days, p = 0.002) than those with normal ABR progression. The difference in the incidence of apnea and bradycardia between infants with and without BE was most pronounced during the first week. CONCLUSIONS: Premature infants with transient bilirubin encephalopathy as defined by abnormal ABR progression in relation to hyperbilirubinemia have more concurrent apneic events and require more prolonged respiratory support and medications.     

Antenatal glucocorticoid treatment decreases mortality and chronic lung disease in survivors among 23- to 28-week gestational age preterm infants

The purpose of this study was to analyze the influence of antenatal glucocorticoid therapy (AGT) on mortality and chronic lung disease (CLD) in surviving preterm infants 23 to 28 weeks gestational age (WGA). This was a multicenter, prospective, observational study. A total of 2448 infants 23 to 28 WGA were born in 2002 to 2003; 27.7% did not receive AGT, 18.8% were exposed to partial AGT, and 53.5% were exposed to complete AGT. A total of 883 died and 22.9% of 1537 survivors were affected by CLD. Unadjusted univariate analysis showed AGT was associated with a reduction in mortality (p<0.001), either with partial or complete AGT courses, and also with a reduction in CLD in survivors (p<0.001), but only with complete AGT courses. In logistic regression analysis adjusted for confounding factors and a propensity score for AGT, AGT was significant and independently associated with a reduction of mortality, but only for complete AGT course (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.47 to 0.87; p=0.004), and with a decrease in CLD if a complete AGT course was administered (OR, 0.63; 95% CI, 0.45 to 0.89; p=0.009). A complete course of AGT in 23 to 28 WGA pregnancies is associated with decreased rates of neonatal mortality and CLD disease in surviving infants.     

Fluid management considerations in extremely preterm infants born at 22-24 weeks of gestation

Emerging data regarding the encouraging outcomes of extremely preterm infants from centers taking active approaches to the care of these infants have prompted dialogue regarding optimal medical management. Among the multitude of decisions providers make in caring for extremely premature infants is the prescribing of parenteral fluids. Surprisingly, there are limited data to guide evidenced-based approaches to fluid and electrolyte management in this population. Immaturity of renal function and skin barriers contribute to the impaired capacity of the preterm infant to maintain salt and water homeostasis. This perspective paper highlights developmental physiological properties of the kidney and skin, which the provider needs to understand to provide parenteral fluid therapy. Additionally, we provide recommendations for initial fluid and electrolyte management of the preterm infant based on novel data as well as the published literature.     

Clinical outcome of small for gestational age preterm infants

Data from 55 preterm SGA infants and 55 preterm AGA infants matched for gestational age and sex were reviewed retrospectively. An increased incidence of perinatal hypoxia (30 vs. 18), gastrointestinal problems, minor infections (27 vs. 9), hematological problems and increased mortality (21.8% vs. 7.2%) was observed in the SGA infants. The incidence of HMD was higher in the AGA group (not significant), but the HMD was much more severe in the SGA group. Mortality as a result of HMD was significantly higher in the SGA group. The percentage of handicapped children is 19% in the SGA group and 9% in the AGA group. The percentages of severely handicapped children are 4.8% and 2.3% respectively. The combination of prematurity and severe intrauterine growth retardation in the SGA group caused a higher mortality and morbidity than was seen in their AGA controls. This clinical performance of SGA preterm infants is important especially for those who have to decide at what moment such a child should be delivered by caesarean section.     

Amplitude-integrated EEG in preterm infants: maturation of background pattern and amplitude voltage with postmenstrual age and gestational age.

OBJECTIVE: Amplitude-integrated electroencephalogram (aEEG) is a single channel EEG recorded from two parietal electrodes. The objective of this study was to test the hypothesis that aEEG maturation follows postmenstrual age (PMA) irrespective of gestational age (GA). METHODS: We recruited inborn infants with a GA <33 weeks and without evidence of neurologic anomaly. Serial aEEG recordings were assessed for: presence of continuous activity and mature sleep-wake cycling (SWC); low base voltage (V), that is, the lowest amplitude margin; high base V, that is, the most common amplitude margin; upper high V, that is, upper margin during highest activity; and span, that is, the difference between upper high and simultaneous high base V. Statistical analysis included logistic regression and repeated measures analysis of variance. RESULTS: We obtained 119 aEEG recordings in 31 preterm infants (GA 25 to 32 weeks; birth weight 600 to 1704 g, PMA 25 to 35 weeks). The frequency of mature SWC increased with PMA independent of GA, while the frequency of continuity increased with PMA and was higher in extremely preterm infants after correcting for PMA. Low base and high base V increased with PMA, while span and upper high V significantly decreased with PMA. In addition, high base V was higher in extremely preterm infants after correcting for PMA. CONCLUSIONS: In preterm infants aEEG matures predominantly with PMA. Our data suggest that some aspects of aEEG maturation are enhanced, rather than inhibited by extremely preterm birth. These data suggest that aEEG in preterm infants may need to be analyzed by comparing results with standards of similar PMA and GA.     

Ontogeny of autonomic regulation in late preterm infants born at 34-37 weeks postmenstrual age

Late preterm infants (34-37 weeks postmenstrual age at birth) are intermediate between less mature preterm infants and infants born at 38 weeks or more in regard to autonomic brain stem maturation. Ventilatory responses to CO(2) in preterm infants born at 33 to 36 week are significantly higher than in infants born at 29 to 32 weeks both at 3 to 4 and 10 to 14 days postnatal age, but do not differ from full-term reference levels. The ventilatory response to hypoxia in preterm infants is biphasic; initial transient hyperventilation is followed by a return to baseline and then a decrease below baseline. In infants born at 32 to 37 weeks, parasympathetic maturation appears significantly less than in full-term infants based on diminished increases in high frequency heart rate variability in quiet sleep, suggesting that late preterm infants are still more susceptible to bradycardia than full-term infants. Both the presence and severity of apnea of prematurity progressively decrease the higher the postmenstrual age. Late preterm infants, however, are still at risk, with prevalence rates as high as 10% compared with about 60% in infants born at <1500 g. The incidence of apparent life-threatening events is more common in preterm infants (8-10%) than full-term infants (1% or less). In the Collaborative Home Infant Monitoring Evaluation studies, the frequency of conventional and extreme events in near term infants is intermediate between preterm infants <34 weeks at birth and full-term infants. The relative risk for at least one extreme event in late preterm infants is increased (5.6 and 7.6, respectively, P < 0.008) compared with full-term infants and remains higher until 43 weeks postmenstrual age. The rate for Sudden Infant Death Syndrome in preterm infants born at 33 to 36 weeks is 1.37/1000 live births compared with 0.69 in infants born full term. Affected late preterm infants die at a older mean postmenstrual age compared with less mature infants (48 and 46 weeks, respectively), but die at a younger postmenstrual age than full-term infants (53 weeks, P < 0.05).     

Population-based study on antenatal corticosteroid treatment in preterm small for gestational age and non-small for gestational age twin infants

Objectives: To assess the associations between antenatal corticosteroid use (ACU), mortality and severe morbidities in preterm, twin neonates and compare these between small for gestational age (SGA) and non-SGA twins.

Materials and methods: Population-based study using data collected by the Israel National Very Low Birth Weight infant database from 1995 to 2012, comprising twin infants of 24–31 weeks' gestation, without major malformations. Univariate and multivariable logistic regression analyses were performed.

Results: Among the 6195 study twin infants, 784 were SGA. Among SGA neonates, ACU were associated with decreased mortality (23.9% vs. 39.2%, p?p?=?0.0015), similar to the effect in non-SGA neonates (mortality 13.0% vs. 24.5%, p?p?P_interaction?=?0.69. Composite adverse outcome risk was also reduced in SGA (OR?=?0.78, 95% CI 0.50–1.23) and non-SGA groups (OR?=?0.78, 95% CI 0.65–0.95), P_interaction?=?0.95.

Conclusions: ACU should be considered in all mothers with twin gestation, at risk for preterm delivery at 24–31 weeks, in order to improve perinatal outcome.     

Significance of low birthweight for gestational age among very preterm infants

Objective To estimate the risk of specific adverse neonatal events resulting from the combined effects of prematurity and low birthweight in very preterm infants (delivered at 24–31 weeks of gestation)
Design A cohort study of specific adverse neonatal events in preterm infants born at between 24 and 31 weeks of gestation.
Setting Pavia, Italy.
Population Two hundred and thirty singleton infants with sonographically confirmed gestational age, delivered at 24 to 31 weeks of gestation.
Methods To evaluate the impact of a lower than expected birthweight on selected neonatal events independently of gestational age, we calculated birthweight standard deviation scores (differences between actual birthweight and fitted birthweight divided by fitted standard deviation) for each week of gestation.
Results After adjustment for gestational age and other confounders, there was a significant linear trend relating a decreasing birthweight SDS to an increased likelihood of neonatal death, intraventricular haemorrhage, severe respiratory distress syndrome, and acidosis. Compared with infants with SDS 0 ( 50th centile of birthweight), infants with birthweight SDS < −1 (< 16th centile) had increased odds for neonatal death [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.42–9.6], grade III-IV intraventricular haemorrhage (OR 17.5, 95% CI 4.04–75.9), and neonatal acidosis (OR 3.22, 95% CI 1.41–7.4). The significance of birthweight SDS as a predictor of neonatal outcome, however, was lower than that of gestational age.
Conclusions A lower than expected birthweight affects the likelihood of several adverse neonatal events in very preterm infants. However, a decreasing birthweight SDS affects neonatal outcome less than decreasing gestation does.     

Clitoral length assessment in newborn infants of 30 to 41 weeks gestational age

Clitoromegaly in the neonatal period is an important morphological sign. There are only few reports establishing an objective assessment of clitoral size. The present study establishes normal standards for clitoral length in healthy premature and full-term infants. The data are expressed at the same time in relation to both gestational age and birth weight, two variables which are strictly intercorrelated. Appropriate curves, which permit an easy and rapid objective determination of clitoral size, are presented.     

Low maternal age and neonatal survival of extremely preterm twins (20-28 weeks of gestation)

OBJECTIVE: We investigated the relationship between low maternal age and neonatal survival among extremely preterm twins. METHODS: This was a retrospective cohort study on live births of extremely preterm twins delivered to teenaged mothers (aged 15-19 years) in the United States within the period 1995 through 1998. Overall neonatal and early and late neonatal mortality in this category was compared with that of a similar group of twins born to young adult mothers (aged 20-29 years). We used the generalized estimating equation framework in computing relative risks after adjusting for intracluster correlations. RESULTS: Analysis involved 2,290 extremely preterm liveborn twins of teenaged mothers and 8,709 born to young adult mothers. Overall, neonatal mortality was 29% higher among the extremely preterm twins born to teenaged mothers (adjusted odds ratio [OR] 1.29; 95% confidence interval [CI] 1.04%, 1.59%). The disparity in neonatal survival was chiefly in the early neonatal period (adjusted OR 1.34; 95% CI 1.07%, 1.67%), while late neonatal mortality was comparable (adjusted OR 0.91; 95% CI 0.58%, 1.42%). In addition, twins of teenaged mothers had significantly higher level of mortality, except for the birth weight category of 1,000-1,499 g. CONCLUSION: Low maternal age was found to be associated with elevated risk of neonatal death among extremely preterm twins. The preponderance of deaths among extremely preterm twins of teenaged mothers in the early neonatal period appeared to be responsible for the disparity in survival. This information may be useful for targeted interventions aimed at enhancing survival of extremely preterm twins born to teenagers, as well as for instituting optimal management options in the clinical setting. LEVEL OF EVIDENCE: II-2     

Vaginal delivery and neonatal outcome in extremely-low-birth-weight infants below 26 weeks of gestational age

Outcomes of extremely-low-birth-weight infants (ELBW) with gestational age below 26 weeks based on mode of delivery (vaginal versus cesarean delivery) were retrospectively compared. During the observation period (1997 to 2000) 48 ELBW infants, below 26 weeks of gestational age, had been admitted to the Neonatal Intensive Care Unit (NICU) of the Department of Pediatrics, University of Freiburg, Germany. Twenty-seven (56%) patients were born vaginally and 21 (44%) by cesarean section. Birth weight, umbilical artery pH, and rectal temperature were significantly lower in the cesarean than in the vaginal group. Clinical Risk Index for Babies (CRIB) score showed significantly (p < 0.005) higher values in the cesarean group compared with the vaginal group. Hypothermia (rectal temperature below 36.2 degrees C after birth) was more common in the cesarean group (48%) than in the vaginal group (33%). Eighty-five percent of the fetuses in the vaginal group received antenatal corticosteroids and 88% in the cesarean group. Survival rate was significantly (p < 0.05) higher in infants born vaginally (78%) than in the cesarean group (43%). Several complications occurred less frequently after vaginal birth than after cesarean section: intraventricular hemorrhage grade III to IV (18 versus 33%); periventricular leukomalacia (4 versus 14%); and neonatal septicemia (33 versus 52%), but not statistical significant. In our study group, extremely immature preterm infants had a more favorable outcome if they were born vaginally when compared with infants delivered by cesarean section.     

Plasma adrenomedullin levels in pregnancies with appropriate for gestational age and small for gestational age infants.

AIMS: To evaluate whether maternal and fetal plasma adrenomedullin levels in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. METHODS: Maternal and fetal circulating adrenomedullin levels were compared between 62 pregnancies with AGA (43 delivered vaginally and 19 delivered by elective cesarean section) and 28 pregnancies with SGA (20 delivered vaginally and 8 delivered by elective cesarean section) at birth. Plasma adrenomedullin levels were measured from maternal and cord venous blood samples using a radioimmunoassay. Umbilical artery blood pH was also measured. RESULTS: There were no significant differences for maternal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. There were also no significant differences for fetal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. In the AGA group delivered vaginally, fetal mature/total adrenomedullin ratio (mean +/- standard error, 16.6 +/- 0.7%) was significantly higher than the maternal ratio (13.8 +/- 0.6%) (p < 0.05). In the SGA group delivered vaginally, fetal mature/total adrenomedullin ratio (18.5 +/- 1.0%) was also significantly higher than the maternal ratio (14.5 +/- 0.6%) (p < 0.05). There was no significant difference in umbilical artery blood pH among the groups. CONCLUSIONS: These results suggest that maternal and fetal plasma circulating adrenomedullin levels may play a role in maternal and fetal cardiovascular adaptation during delivery in pregnancies with both AGA and SGA infants.     

Cyclooxygenase immunohistochemical staining in the human ductus arteriosus after 24 weeks of gestational age

Cyclooxygenase inhibitors (CI) which contained risks to fetal health were one of the most effective tocolytics. In order to indirectly investigate the effects of CI in human ductus arteriosus, immunohistochemical staining for cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2) was evaluated in post-mortem fetuses with gestational ages between 24 and 34 weeks. Neither COX1 nor COX2 staining was related to gestational age. COX1 and COX2 staining in the vessel walls were not related to each other. COX1 staining in the endothelium, inner media and outer media were positively correlated with each other (COX1 endothelium vs IM staining Spearman's rho statistic [rs] = 0.721, p = 0.001; COX1 endothelium vs OM staining [rs] = 0.634, p = 0.004; COX1 IM vs OM staining [rs] = 0.931, p = 0.001). COX2 staining of endothelium was not correlated with either IM or OM staining. In conclusion, COX2 staining in the post-mortem specimens of human ductus arteriosus between 24 and 34 weeks is weak and limited to the endothelium.     

Life events and low birthweight--analysis by infants preterm and small for gestational age

Social stress was assessed in 92 women with low-birthweight babies and 92 controls using the detailed LEDS measure of life events and severe chronic difficulties. The low-birthweight group was divided into preterm delivery (n = 40), small for gestational age (SGA) (n = 40) and mixed groups. Multivariate analysis was performed using a binomial-logit model to examine whether social factors were independently and significantly associated with low birthweight once the effect of demographic factors, obstetric factors and smoking/drinking were taken into account. Comparison of preterm births with controls indicated that three factors were significantly associated: a previous low-birthweight baby, severe life event/difficulty and bleeding during pregnancy. For SGA babies the factors were: previous low-birthweight baby, low social support and smoking. By using a reliable measure of life events and adequate numbers of low-birthweight babies, this study overcame the potential inaccuracies of previous studies and indicates a more specific relation between social stress and low birthweight.     

Short-term outcomes comparison between preterm infants with and without acute hypoxic respiratory failure attributable to presumed pulmonary hypoplasia after prolonged preterm premature rupture of membranes before 25 gestational weeks

Objective: To determine the updated outcomes of preterm infants with acute hypoxic respiratory failure attributable to presumed pulmonary hypoplasia (PH) following maternal midtrimester prolonged preterm premature rupture of membranes (PPROM).

Study design: Among preterm infants with birthweight <1500?g and 23–34 weeks gestational age in a single center, infants exposed to maternal prolonged (≥7 days) PPROM before 25 gestational weeks (PPPROM25, n?=?76) were retrospectively reviewed. They were 1:1 matched with infants of matched control group (n?=?76) who were unexposed to or exposed to maternal PPROM within 24?hours of delivery by year, gestational age, and weight at birth, sex, and antenatal steroid exposure. The PPPROM25 group was subdivided into infants with and without acute hypoxic respiratory failure attributable to PH (with PH, n?=?20, without PH, n?=?56, respectively). Clinical characteristics and major outcomes were compared. Risk factors for mortality and morbidity were analyzed using a multivariate logistic regression in the PPPROM25 group.

Results: The PH incidence rates were 1.3 and 26.3% and in the matched control and PPPROM25 group, respectively (p?p?>?.05); 87.5 in the PPPROM25 group without PH and 65.0% in group with PH, respectively (p?Conclusions: Despite the improved outcomes in the infants with maternal prolonged PPROM before 25 gestational weeks, presumed PH is still a significant risk factor for their mortality and morbidity.     

Neonatal screening for congenital cytomegalovirus infection in preterm and small for gestational age infants

Abstract

Congenital cytomegalovirus (CMV) infection affects many organs: reticuloendothelial and central nervous system are particularly involved. Congenital CMV infection is the leading cause of non-genetic sensorineural hearing loss. Hearing impairment can be present at birth or it can occur months or even years after birth. It is as well an important risk factor for antenatal stillbirth, preterm birth and small for gestational age (SGA) condition. For these reasons we should early identify congenital CMV infection investigating at least at risk newborns such as preterm or SGA babies given that a simple and standardized method for a large scale screening program is lacking. In our study, we found an association between congenital CMV infection and preterm births (3.03%) and with SGA condition (3.7%). Consequently, routine CMV urine detection should be performed at least in all babies born before 37 weeks of gestational age and in term SGA newborns.