Effect of maternal age on neonatal outcomes in very low birth weight singleton infants: a population-based study.

BACKGROUND: Little is known on the impact of maternal age (MA) on very low birth weight (VLBW) infants' outcomes. We tested the hypothesis that at both ends of MA there are increased adverse neonatal outcomes in VLBW infants. METHODS: We used the Israel National Neonatal Network VLBW (≤1500 g) database. Maternal age was stratified as: <20, 20-24, 25-34 (reference group), 35-39 and ≥40 years. Statistical analyses were univariate and multivariable logistic regression analysis. RESULTS: After adjustment, the infant outcomes of older mothers were similar to those of the reference group for mortality, RDS, severe ROP, NEC and sepsis. Mothers < 20 and 20-24 years old had higher odds of IVH grades 3-4 (OR 1.45, 95% CI 1.09-1.93 and OR 1.26, 95% CI 1.10-1.45, respectively), and BPD (OR 1.55, 95% CI 1.13-2.13 and OR 1.40, 95% CI 1.22-1.62, respectively). There were higher odds for PVL in infants of <20 year-old mothers (OR 1.83, 95% CI 1.26-2.65) and in infants of 35-39 year-old mothers (OR 1.38, 95% CI 1.12-1.69). Poor composite outcomes were significantly higher in the youngest maternal age categories (<20-year-old mothers (OR 1.63, 95% CI 1.28-2.08), and 20-24-year-old (OR 1.28, 95% CI 1.15-1.43). CONCLUSIONS: Neonatal outcomes differ in relation to maternal age among very low birth weight newborns, with adverse outcomes more predominant in infants of younger mothers.

Correlation between prenatal and postnatal penile and clitoral measurements.

BACKGROUND: A correlation between prenatal and postnatal penile and clitoral sizes has not been reported. These data would substantiate the ability of prenatal ultrasound (US) scan to predict postnatal measurements. The aims were to correlate prenatal and postnatal penile and clitoral measurements and to ascertain the possible advantage of using prenatal penile width rather than length to predict postnatal measurements. METHODS: This was a longitudinal study. Fetal penis and clitoris were measured by high-resolution US between gestational weeks 14 and 29. Postnatal measurements of external genitalia were performed during the first postnatal week. All measurements were performed twice consecutively. A correlation between the measurements sets was sought. RESULTS: Paired prenatal and postnatal measurements were performed on 46 males and 48 females. Prenatal penile and clitoral length values correlated significantly with postnatal length at p < 0.05 each. CONCLUSIONS: Prenatal US findings appear to be reliable indicators of postnatal penile and clitoral length measurements. Penile width measurement did not add new information.

Parental and perinatal factors affecting childhood anthropometry of very-low-birth-weight premature infants: a population-based survey.

BACKGROUND: The perinatal-neonatal course of very-low-birth-weight (VLBW) infants might affect their childhood growth. We evaluated the effect of parental anthropometry and perinatal and neonatal morbidity of VLBW neonates on their childhood growth. METHODS: We obtained parental anthropometry, height and weight at age 6-10.5 years of 334 children born as VLBW infants. Parental, perinatal and neonatal data of these children were tested for association with childhood anthropometry. RESULTS: (1) Maternal and paternal weight standard deviation score (SDS) and discharge weight (DW) SDS were associated with childhood weight SDS (R(2)= 0.111, p < 0.00001); (2) Maternal and paternal height SDS, corrected gestational age (GA) at discharge, maternal assisted reproduction and SGA status were associated with childhood height SDS (R(2)= 0.208, p < 0.00001); (3) paternal weight SDS, DW SDS and surfactant therapy were associated with childhood body mass index (BMI) SDS (R(2)= 0.096, p < 0.00001). 31.1% of VLBW infants had DW SDS < -1.88, and are to be considered small for gestational age ('SGA'). One quarter of these infants did not catch up by age 6-10.5 years. CONCLUSION: Childhood anthropometry of VLBW infants depends on parental anthropometry, postnatal respiratory morbidity and growth parameters at birth and at discharge. Almost one-third of VLBW premature infants had growth restriction at discharge from neonatal intensive care unit (NICU), a quarter of whom did not catch up by age 6-10.5 years.

Vitamin E levels during early iron supplementation in preterm infants.

On the basis of preliminary data, this larger bi-institutional continuation trial evaluating the efficacy and safety of early iron supplementation in preterm infants calls attention to the levels of vitamin E, a marker of antioxidant activity, during iron treatment. A total of 116 preterm infants were randomly assigned to receive at 2 or 4 weeks of age ( N = 62, N = 54, respectively) 5 mg/kg/d of nonionic iron polymaltose complex concomitantly with a daily dose of 25 IU vitamin E (as dl-alpha-tocopherol acetate) from 2 weeks of age. Vitamin E (alpha-tocopherol) levels, iron, ferritin, hemoglobin concentration, and reticulocyte count were recorded from 2 to 8 weeks of age. The morbidities of prematurity associated with free radicals formation were also documented. A gradual increase of alpha-tocopherol levels within physiological range (0.8 to 3.5 mg/dL) was found in the 2-week and 4-week groups during the study period with no difference among the groups ( P > 0.05 for all comparisons). At 8 weeks of age, iron and ferritin levels, hemoglobin concentration, and reticulocyte count were higher in the 2-week group. No correlation was observed between timing of both iron and vitamin E supplement and hemolysis or morbidities associated with prematurity. Thus, treatment of iron with vitamin E supplement at 2 weeks of age is, in our experience, an efficacious and safe treatment for improving anemia in preterm infants.

Neonatal seizures: dilemmas in workup and management.

There is a pressing need for consistent, evidence-based guidelines in the management of neonatal seizures by pediatric neurologists and neonatologists. Israeli pediatric neurologists and neonatologists completed a 20-item, self-administered questionnaire on choices of antiepileptic drugs, treatment of intractable neonatal seizures (unremitting seizures after 3 medications), treatment duration, and recommended workup. The responding 36/55 (65%) neurologists and 66/112 (59%) neonatologists made similar antiepileptic drug choices (phenobarbital as first line, phenytoin as second line, and benzodiazepines as third line). Antiepileptic treatment duration was similar for both groups, but varied considerably within them (range, 1-52 weeks). Neurologists tended to recommend longer treatment for seizures secondary to asphyxia or hemorrhage. Neurologists and neonatologists recommended different antiepileptic drugs for intractable neonatal seizures: valproic acid and topiramate by neurologists, vs lidocaine and benzodiazepines by neonatologists (P = 0.0023). Fewer neurologists recommended continuous electroencephalography monitoring after asphyxia than neonatologists (40% vs 70.5%, P = 0.013). These responses reflect both similarities and inconsistencies of the two groups in diagnosing and treating neonatal seizures. Our findings call for controlled clinical trials to establish protocols for (1) diagnosing neonatal seizures, (2) studying the efficacy and safety of new-generation antiepileptic drugs, and (3) determining optimal duration of drug administration.

Candidal versus bacterial late-onset sepsis in very low birthweight infants in Israel: a national survey.

Candidal infections are one of the common causes of late-onset sepsis (LOS) among very low birthweight (VLBW) infants, and are associated with substantial morbidity and mortality. The aim of this study was to evaluate the perinatal and neonatal risk factors for fungal LOS compared with bacterial LOS in VLBW infants. This was a population-based observational study of VLBW infants in 28 neonatal intensive care units across Israel, with information on 11,830 infants born between 1995 and 2002 from the Israeli National VLBW infant database. The study population comprised 3054 infants with one or more episodes of LOS. Univariate analysis and logistic regression models were used to compare perinatal and neonatal risk factors between infants with fungal sepsis only (N=179) and those with bacterial sepsis only (N=2630). The mean birthweight and gestational age of infants with candidal LOS were significantly lower (940 g; 27.1 weeks) than those in the bacterial LOS group (1027 g; 28.3 weeks) (P<0.001). Logistic regression analysis showed that candidal sepsis, in contrast to bacterial sepsis, was independently associated with decreasing gestational age and bronchopulmonary dysplasia (BPD). In addition, BPD only [odds ratio (OR) 1.84; 95% confidence intervals (CI) 1.03-3.23] and BPD with postnatal steroid therapy (OR 2.66; 95% CI 1.59-4.46) were independently associated with an increased risk for candidal sepsis.

Unusual presentation of familial glucocorticoid deficiency with a novel MRAP mutation.

CONTEXT: Mutations in MRAP, an interacting partner of the ACTH receptor, have been shown recently to cause familial glucocorticoid deficiency (FGD) in kindreds with confirmed FGD and no ACTH receptor mutations. OBJECTIVE: We describe a Jewish-Ethiopian family with FGD caused by a novel MRAP mutation. PATIENTS: Our index patient presented at the age of 19 months with hypocortisolism, severe psychomotor retardation, myoclonic seizures, spastic quadriparesis, and microcephaly. Before the definite diagnosis was made, a female sibling was born in another hospital and succumbed during the neonatal period due to sepsis and adrenal crisis. METHODS: DNA was extracted from peripheral blood samples from the index case and his mother and from fibroblasts obtained from the female patient. The DAX-1, ACTH receptor (MC2R), and MRAP genes were analyzed. RESULTS: The index patient was diagnosed with FGD and was found to be homozygous for a novel MRAP mutation, a seven-base deletion in exon 3 of the MRAP gene. This deletion causes a frame shift, resulting in a stop codon after 23 amino acids (L31X). Postmortem analysis of fibroblasts obtained from the female patient revealed that she harbored the same mutation. CONCLUSIONS: This is the first report of MRAP mutations after the recent identification of the gene. Whether the novel MRAP mutation described by us is associated with a particularly severe phenotype remains to be investigated.

Impact of maternal diabetes mellitus on mortality and morbidity of preterm infants (24-33 weeks' gestation).

OBJECTIVE: We hypothesized that maternal diabetes mellitus (DM) increases the risk for mortality, respiratory distress syndrome (RDS), and major complications of prematurity. METHODS: Analysis of prospectively collected (1995-2007) Israel National Very Low Birth Weight Infant Database. Maternal DM was recorded as pregestational or gestational. Multivariable logistic regression analysis was used to assess the independent effect of maternal DM status on infant mortality, RDS, and other complications of prematurity. RESULTS: Infants of mothers with pregestational (n = 120) and gestational (n = 825) DM were similar, and their data were pooled for analyses. Mothers with DM were more likely to have received a complete course of prenatal steroids than control mothers. Infants of diabetic mothers (IDM) had a slightly higher gestational age and birthweight than non-IDM's. Distribution of birthweight percentiles and the mean birthweight z scores were similar. Apgar scores were statistically higher in the IDM group. There were no significant differences between the 2 groups in terms of delivery room mortality, RDS, and other major complications of prematurity. Total mortality and bronchopulmonary dysplasia rates were significantly higher in the nondiabetic group. The adjusted odds ratios for mortality, RDS, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, and patent ductus arteriosus were not significantly increased in the IDM group. CONCLUSIONS: With modern management and adequate prenatal care, IDM born very low birthweight do not seem to be at an excess risk of developing RDS or other major complications of prematurity compared with non-IDM.

Does admission hypothermia predispose to intraventricular hemorrhage in very-low-birth-weight infants?

BACKGROUND: The etiology of intraventricular hemorrhage (IVH) in very-low-birth-weight (VLBW) infants is multifactorial and is associated with low gestational age (GA) and severity of neonatal respiratory disease. The role of admission hypothermia (AHT) in the pathogenesis of IVH in VLBW infants has not yet been elucidated. We searched risk factors for IVH in VLBW infants while focusing on AHT. PATIENTS AND METHODS: VLBW infants ≤33 weeks' gestation from three participating medical centers were included. From patients' medical charts we collected variables known to be associated with IVH, focusing on AHT. AHT was defined as rectal temperature ≤35.5°C at admission to the NICU. Head ultrasound was performed at 2-5 and 6-10 days of age and before discharge. RESULTS: 271 VLBW infants were studied. Univariate analysis showed that AHT at ≤35.5°C was not significantly associated with IVH (all grades; p = 0.16), but associated with IVH grade 3-4 (p = 0.034), while AHT at ≤35°C was significantly associated with IVH (p = 0.036) and with IVH grade 3-4 (p = 0.003). Multivariate logistic regression analysis showed that AHT (at ≤35.5 and at ≤35°C) were not associated with IVH. Only four variables were independently significantly associated with IVH: GA, use of nitric oxide, hypocarbia and base deficit >10. Four variables were strongly associated with severe IVH (grades 3-4): GA, hypotension, base deficit >10 and hyponatremia. CONCLUSIONS: In VLBW infants, AHT at ≤35.5 and at ≤35.0°C were not significantly associated with IVH. GA, use of nitric oxide, hypocarbia and base deficit >10 were strongly associated with IVH.

Brain diffusivity in infants with hypoxic-ischemic encephalopathy following whole body hypothermia: preliminary results.

Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.

The efficacy and safety of early supplementation of iron polymaltose complex in preterm infants.

The purpose of this study was to examine the efficacy and safety of early nonionic iron supplementation in preterm infants. Infants with gestational age < or = 32 weeks who were fed enriched human milk were assigned concurrently to receive 5 mg/kg/d enteral iron polymaltose complex (IPC) at 2 or 4 weeks of age. The levels of hemoglobin, reticulocytes, serum iron, ferritin, and soluble transferrin receptor were recorded at 2, 4, and 8 weeks of age. The incidence of morbidities associated with prematurity and the need for red blood cell transfusions (RBCTs) were recorded. The 2-week group (n = 32) had a better iron status than the 4-week group (n = 36) at 4 weeks and at 8 weeks of age. The incidence of morbidities associated with prematurity was not different among the groups ( P = 0.26). RBCT was required in one infants of the 2-week group and in 10 infants in the 4-week group ( P = 0.045). The number needed to treat to prevent one RBCT was five. Supplementation of 5 mg/kg/d enteral IPC to preterm infants fed enriched human milk as early as 2 weeks of age was more beneficial to iron status than at 4 weeks of age, and was associated with decreased need for RBCTs and no increase in the incidence of morbidities associated with prematurity.