Delivery room resuscitation and adverse outcomes among very low birth weight preterm infants.

OBJECTIVE: To evaluate risk factors and impact of delivery room cardiopulmonary resuscitation (DR-CPR) on very low birth weight (VLBW) preterm infants. STUDY DESIGN: A national, population-based, observational study evaluating risk factors and short-term neonatal outcomes associated with DR-CPR among VLBW, extremely preterm infants (EPIs, 24 to 27 weeks' gestation) and very preterm infants (VPI, 28 to 31 weeks' gestation) born in 1995 to 2010. RESULTS: Among 17 564 VLBW infants, 636 (3.6%) required DR-CPR. In the group of 6478 EPI, 412 (6.4%) received DR-CPR compared with 224 of 11 086 infants (2.0%) in the VPI group. EPI who underwent DR-CPR had higher odds ratios (ORs (95% confidence interval)) for mortality compared to EPI not requiring DR-CPR (OR 3.32 (2.58, 4.29)), grades 3 to 4 intraventricular hemorrhage (IVH) (OR 1.59 (1.20, 2.10)) and periventricular leukomalacia (OR 1.81 (1.17, 2.82)). DR-CPR among VPI was associated with higher ORs for mortality (OR 4.99 (3.59, 6.94)), early sepsis (OR 2.07 (1.05, 4.09)), grades 3 to 4 IVH (OR 3.74 (2.55, 5.50)) and grades 3 to 4 retinopathy of prematurity (ROP) (OR 2.53 (1.18, 5.41)) compared to VPI not requiring DR-CPR. Only 11% of infants in the EPI DR-CPR group had favorable outcomes compared with 44% in the VPI DR-CPR group. Significantly higher ORs for mortality, IVH and ROP were found in the VPI compared to the EPI group. CONCLUSION: Preterm VLBW infants requiring DR-CPR were at increased risk of adverse outcomes compared to those not requiring CPR. This effect was more pronounced in the VPI group.

Perinatal factors associated with active intensive treatment at the border of viability: a population-based study.

OBJECTIVE: The aim of this national population-based study was to identify perinatal and neonatal factors associated with active intensive treatment (AIT) of infants born at the periviable period of 22 to 24 weeks of gestation. STUDY DESIGN: Data from the Israel national very low-birth weight infant database on 2207 infants born alive in 1995 to 2010 at gestational age (GA) 22 to 24 weeks were evaluated. AIT was defined as endotracheal intubation in the delivery room or mechanical ventilation in the neonatal intensive care unit. Multivariable logistic regression analyses were used to identify the independent effect of demographic and perinatal factors on AIT for each gestational week. RESULT: Of the 2207 infants born at 22 to 24 weeks GA, 1643 (74.4%) received AIT and 564 (25.6%) received comfort care. AIT increased from 25.5% at 22 weeks to 62.7 and 93.5% at 23 and 24 weeks GA, respectively, reflecting a 4.66 (95% confidence interval (CI) 3.32 to 6.54)- and 29.8 (95% CI 19.9 to 44.6)-fold odds for AIT at 23 and 24 weeks GA, respectively, compared with 22-week GA infants. Perinatal treatments associated with AIT included maternal tocolytic therapy (odds ratio (OR) 1.51, 95% CI 1.04 to 2.20), prenatal steroid therapy, both partial (OR 3.30, 95% CI 2.14 to 5.10) and complete (OR 3.17, 95% CI 1.91 to 5.26) and cesarean delivery (OR 2.68, 95% CI 1.88 to 3.83). Each unit increase in birth weight z-score was associated with an OR of 1.58 (95% CI 1.30 to 1.92) for AIT. At 22 weeks GA, maternal tocolytic treatment was associated with higher odds of AIT. In the 23 and 24-week GA infants, maternal infertility treatment, antenatal steroids, cesarean delivery and higher-birth weight z-scores were significantly associated with AIT. Among 23-week GA infants, AIT decreased significantly in the period 2006 to 2010 compared with 1995 to 2000 (OR 0.51, 95% CI 0.34 to 0.77). CONCLUSION: An active approach in obstetric management of pregnancies appears to impact the neonatologists' decision to undertake AIT treatment in infants born at the border of viability. The higher odds for AIT associated with obstetric interventions might contribute to the reported beneficial effect of antenatal steroids and cesarean delivery on the survival of infants born at the border of viability.

Effects of prone and supine positions on sleep state and stress responses in preterm infants.

AIM: The purpose of the study is to assess the influence of prone or supine position on sleep states and on withdrawal and approach reactions of preterm infants. METHODS: Thirty-two preterm infants from Meir Medical Center, Israel, mean post menstrual age 30.37±2.57, mean birth weight 1250g±313.86, participated in the study. Infants were studied during 48h. Positions (prone and supine) were alternated every 3-4h after feedings. Sleep states were assessed by Actigraph measurement and by two daily 30-min Naturalistic Observations of Newborn Behavior (NONB) to confirm sleep states and for recording the behavioral reactions (approach and withdrawal). RESULTS: In the prone position there were more approach reactions as compared to withdrawal reactions (p<.001) while in the supine position, the approach and withdrawal reactions were comparable. In the prone position more sleep patterns (deep sleep, light sleep, drowsy) were observed as opposed to more awake patterns (quiet awake, active awake and agitated fussy) that were seen in the supine position. CONCLUSIONS: Clinical implications encourage placing the preterm infant in the prone position while in the NICU. This enables important achievements such as longer periods of quality sleep, and production of adaptive self-regulatory reactions.

Iron supplementation for preterm infants receiving restrictive red blood cell transfusions: reassessment of practice safety.

OBJECTIVE: To reassess iron supplementation practice safety in very low birth weight (VLBW) preterm infants receiving restrictive red blood cell transfusions during initial hospitalization. STUDY DESIGN: Iron status, including hemoglobin (Hb), serum iron, ferritin, and soluble transferrin receptor (sTfR) levels and reticulocyte count of transfused (n=236) and non-transfused (n=166) preterm infants at ≤24 h and 2, 4 and 8 weeks were recorded. As per protocol, a restrictive blood transfusion policy and supplementation of 5 mg kg(-1) per day of iron polymaltose complex from 4 weeks and 25 mg(-1) per day of vitamin E from 2 weeks were imposed for all infants. Normative reference cord-blood ferritin value of preterm infants was used for comparison. Vitamin E levels and incidence of morbidities associated with prematurity were recorded. RESULT: At ≤24 h, the characteristics and iron status of both groups were similar. At 2, 4 and 8 weeks, the transfused group had significantly higher Hb, iron and ferritin levels; sTfR levels were lower at 4 and 8 weeks (all indices, P<0.05). At 8 weeks, the median ferritin levels of our transfused group were lower than that of normative reference cord-blood value (115 (50th percentile) vs 79 (43 to 107) µg l(-1), respectively). Vitamin E levels and the incidence of morbidities associated with prematurity of the transfused and non-transfused groups were not different (both indices, P>0.18). CONCLUSION: Adding iron supplementation to preterm infants receiving restrictive blood transfusions has shown to be a judicious and safe practice in terms of iron status for VLBW preterm infants.

Meconium periorchitis: intrauterine diagnosis and neonatal outcome: case reports and review of the literature.

Meconium periorchitis (MP) is a rare disorder caused by fetal meconium peritonitis with subsequent spillage of meconium into the scrotal sac. The condition is seldom diagnosed correctly during fetal life and the ultrasonographic diagnoses reported vary from no diagnosis to hematoma or hydrocele. It is usually diagnosed clinically during the first year of life when a scrotal mass is an incidental finding. Here, we describe two cases of MP that were diagnosed during routine intrauterine ultrasound examination for fetal growth assessment, and confirmed after birth. One infant underwent a surgical excision of the scrotal mass, confirming the histological diagnosis of meconium periorchitis. The other was managed conservatively. Neither had cystic fibrosis. Thus, we believe that a diagnosis of MP should be considered when prenatal ultrasonographic findings are suspicious for the problem. The awareness of the ultrasonographer and the neonatologist are important for immediate postnatal management, as congenital scrotal masses may have other etiologies.

Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation.

Three patients born to the same set of consanguineous parents presented with antenatal skin oedema, hypotonia, cardiomyopathy and tubulopathy. The enzymatic activities of multiple mitochondrial respiratory chain complexes were reduced in muscle. Marked reduction of 12s rRNA, the core of the mitochondrial small ribosomal subunit, was found in fibroblasts. Homozygosity mapping led to the identification of a mutation in the MRPS22 gene, which encodes a mitochondrial ribosomal protein. Transfection of the patient cells with wild-type MRPS22 cDNA increased the 12s rRNA content and normalised the enzymatic activities. Quantification of mitochondrial transcripts is advisable in patients with multiple defects of the mitochondrial respiratory chain.

Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis.

OBJECTIVES: To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit. STUDY DESIGN: Full-term infants <72 h of age, who had risk factors and/or were suspected of having sepsis, were eligible for study. The levels of SAA were taken at 0, 24 and 48 h post sepsis evaluation. Thirty matched infants served as a control group for comparing SAA concentrations. RESULTS: Of 104 infants eligible for entry to the study, 23 had sepsis and 81 had not sepsis. The SAA levels of the septic group were significantly higher than those of the nonseptic group at 0, 24 and 48 h (P<0.01 for all time points). In comparison with C-reactive protein (CRP), SAA levels rose earlier and in a sharper manner, had higher levels and returned faster to normal values in infants with early onset sepsis. At 0 h post-sepsis evaluation, serum SAA had an overall better diagnostic accuracy for predicting early onset sepsis than CRP (sensitivity (96 vs 30%), specificity (95 vs 98%), positive predictive value (85 vs 78%), negative predictive value (99 vs 83%), positive likelihood ratio (19 vs 12), and negative likelihood ratio (0.05 vs 0.71). CONCLUSIONS: SSA is advocated as an inflammatory marker of neonatal early-onset sepsis.

Assisted exercise and bone strength in preterm infants.

Studies have previously demonstrated that brief (4 weeks) passive range-of-motion exercise is beneficial for bone development in very low birth weight (VLBW) preterm infants. However, the optimal duration of exercise for bone development in preterm infants is yet unknown. The aim of the present study was to examine the effect of 8 weeks of assisted exercise on bone strength and metabolism in VLBW premature infants. Sixteen infants (mean +/- standard error of the mean birth weight 1,009 +/- 55 g and gestational age 27.3 +/- 0.3 weeks) were randomly assigned into exercise (n = 8) and control (n = 8) groups. The intervention started at the first week of life and involved 8 weeks of daily passive extension and flexion range-of-motion exercise of the upper and lower extremities. Biochemical markers of bone turnover were measured at enrollment and after 8 weeks. Bone strength was measured weekly by quantitative ultrasound measurement of tibial bone speed of sound (SOS). Bone SOS decreased significantly in the control group (-108.1 +/- 33.7 m/second, P < 0.0001) during the study period, while remaining stable in the exercise group (11.3 +/- 22.8 m/second). The main beneficial effect of exercise occurred in the first 4 weeks of the intervention. There were no significant differences in the bone turnover marker changes between the groups. There is a significant postnatal decrease in bone SOS in VLBW preterm infants. Eight weeks of assisted range-of-motion exercise attenuates the decrease in bone strength and may decrease the risk of osteopenia in premature infants.

Aspirin treatment for neonatal infectious endocarditis.

We describe a term female neonate with Serratia marcescens endocarditis. Despite adequate antibiotic therapy for 8 days, the bacteremia persisted and there was an increase in vegetation size. Treatment with aspirin was initiated, with resolution of the bacteremia and a gradual decrease in vegetation size. We conclude that in neonatal endocarditis, aspirin may be beneficial additional treatment.

Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions.

We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B6. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.

Evidence for exercise-induced bone formation in premature infants.

We assessed the effect of a four weeks exercise training intervention on bone turnover markers in premature infants. Twenty-four very low birth weight premature infants were matched for gestational age, birth weight, gender, as well as for corrected age and weight at initiation of the study. Then the subjects were randomly divided into an exercise (n = 12) and a control group (n = 12). Exercise consisted of passive range of motion exercise with gentle compression of both the upper and lower extremities lasting 5 - 10 minutes each day, 5 days per week for 4 weeks. This protocol has been shown to increase bone mineral density in premature infants. Bone formation was assessed by measurements of circulating bone specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP). Bone resorption was determined by serum measurements of C- terminal cross-links telopeptide of type-I collagen (ICTP). Training led to a significant (P < 0.05) increase in weight gain (767 +/- 49 versus 586 +/- 24 gr in trained and control premature infants, respectively); and to a significant increase in BSAP (37.2 +/- 14.6 versus 4.1 +/- 8.4 % in trained and control premature infants, respectively). PICP increased also following exercise (34.6 +/- 18.9 versus 5.4 +/- 9.1 % in trained and control subjects, respectively), however, this increase was not statistically significant. Exercise led to a significant decrease in ICTP (-24.7 +/- 3.1 versus -5.5 +/- 5.4 % in trained and control subjects, respectively). A relatively brief exercise intervention was associated with a biochemical evidence of bone formation in very low birth weight premature infants.

Preterm labour at 34--36 weeks of gestation: should it be arrested?

Currently, preterm labour is treated with tocolytic agents and prenatal steroids until the 34th week of gestation only. Our objective in this study was to assess this practice. Seven-year records of all preterm infants born in our institution at 34--36 weeks of gestation, were evaluated retrospectively. All babies, born in singleton well-dated pregnancies, without maternal, medical or obstetric complications, and by normal vaginal delivery, were included. Their length of hospital stay and perinatal complications were compared across gestational age groups of 34, 35 and 36 weeks. Of the 207 babies included, statistically significant reductions in the rates of respiratory distress syndrome (15.0% vs. 3.2%), nosocomial sepsis (5.0% vs. 0%) and apnoea of prematurity (11.7% vs. 2.2%), and consequently, in length of hospital stay (16 +/- 2.7 vs. 4 +/- 0.3 days) occurred between 34 and 36 weeks of gestation. The severity of respiratory distress syndrome also declined significantly. The changes were most noticeable after 35 weeks of gestation, and it was concluded that neonatal complications are still prevalent at 34 and 35 weeks. Therefore, we propose that labour should not be induced at 34 and 35 weeks of gestation and that tocolytic agents and maternal prenatal steroids may be considered in preterm labour during this period.

Measurements of bone turnover markers in premature infants.

We determined the levels of circulating bone turnover markers in preterm infants during the first weeks of life. Twenty premature infants (mean gestational age 27+/-2.2 weeks, mean birth weight 894+/-231 g) hospitalized in the neonatal intensive care unit (NICU) at the Meir General Hospital, Israel, participated in the study. Measurements of bone turnover markers were performed at birth, and every week thereafter for an average follow-up of 11.2+/-0.7 weeks. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of serum levels of the carboxy-terminal cross-links telopeptide of type I collagen (ICTP). All three markers of osteoblastic activity increased markedly and significantly during the first three weeks of life, and then continued to increase gradually until week 10 (p<0.01). Circulating ICTP levels increased in the first week of life and then decreased gradually throughout the follow-up (p<0.01). The study participants were divided into premature infants born at extremely low birth weight (ELBW: <1000 g, n=12) and very low birth weight (VLBW: 1000-1250 g, n=8). Osteocalcin (in weeks 2-5 of life), PICP (weeks 3-5), and ICTP levels (weeks 2-3) were significantly higher in VLBW preterms. These results suggest increased bone formation in premature infants in the first three months of life. The increased bone turnover in VLBW compared to ELBW premature infants may be the result of a generally higher morbidity in ELBW preterm infants in early stages of life.

Dichloroacetate treatment for severe refractory metabolic acidosis during neonatal sepsis.

We describe a preterm neonate with documented group B Streptococcus sepsis and associated metabolic acidosis whose lactic acidemia was refractory to conventional sodium bicarbonate therapy but responded well to dichloroacetate treatment.

Quantitative ultrasound measurements of bone speed of sound in premature infants.

UNLABELLED: We measured bone speed of sound in premature infants by quantitative ultrasound. A total of 44 neonates participated in the study including 29 premature infants (median birth weight 1264 g, range 578-2420 g; median gestational age 31 weeks, range 24-36 weeks) and 15 full-term infants (median birth weight 3360 g, range 2700-3730 g; median gestational age 40 weeks, range 37-41 weeks). The left tibial speed of sound (SOS) was measured by quantitative ultrasound. Bone SOS was successfully measured in all infants. We found a significant correlation between tibial SOS and gestational age (r = 0.78, P < 0.0005), but a significant inverse correlation between tibial SOS and post-natal age (r = -0.78, P < 0.0005). Bone SOS was significantly (P < 0.05) higher in full-term infants (3101 m/s, range 2899-3314 m/s) compared to premature infants (2821 m/s, range 2516-3139 m/s), and compared to a subgroup of the premature infants who reached corrected age of full-term infants (2706 m/s, range 2516-2892 m/s, n = 13). Bone SOS was lower (2745 m/s, range 2533-3036 m/s, n = 16) in very low birth weight premature infants (birth weight < 1500 g). CONCLUSION: The results indicate that tibial speed of sound was reduced in premature infants (in particular very low birth weight) compared to full-term infants even when premature infants reached the corrected age of their full-term peers. The potential role of this technique in assessing osteopenia in premature infants warrants further exploration.

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Prenatal diagnosis for detecting congenital malformations: acceptance among Israeli Arab women.

BACKGROUND: A high rate of consanguineous marriages exists within the Israeli Arab community, with approximately half occurring between first cousins. This contributes towards a high incidence of congenital malformations and autosomal recessive diseases, many of which are detectable at prenatal diagnosis. OBJECTIVES: To assess the levels of both awareness and acceptance regarding prenatal diagnosis and termination of pregnancy among a group of Arab women in order to devise the optimal means of providing genetic counseling and general health services. METHODS: A total of 231 Arab women of childbearing age were interviewed 3 days postpartum to assess their knowledge of prenatal diagnosis and termination of pregnancy, their willingness to undergo prenatal diagnosis, and their opinions on termination of pregnancy in the event of a severely affected fetus. RESULTS: Half the women believed that prenatal testing is not an effective (or accurate) tool for diagnosing an affected fetus. A quarter had poor knowledge on prenatal diagnosis, and a quarter believed that prenatal diagnosis does provide the correct diagnosis. Ninety-five percent said they would agree to undergo prenatal diagnosis; and in the event of a severely affected fetus, 36% said they would agree to a termination of pregnancy, 57% said they would not, and 7% were undecided. CONCLUSIONS: There is a need for special intervention programs, with guidance by health professionals, geneticists and religious authorities, that will inform this population on the increased risk associated with consanguinity, stress the importance and effectiveness of prenatal testing to identify severe congenital malformations, and help them to accept prenatal diagnosis and termination of pregnancy if indicated.

Fetal intrathoracic injuries following mild maternal motor vehicle accident.

Reported herein are the cases of three infants who were born with serious intrathoracic injuries, apparently sustained at the time of the mother's involvement in a motor vehicle accident. The accidents occurred at 26th, 29th and 36th weeks of pregnancy and resulted in minimal injuries to the mothers themselves. The infants were born four weeks, three hours and two days later, respectively. Their injuries were manifested (singly) by hemothorax, pneumothorax and contusion of lung, the latter in a setting of multi-organ trauma. We suggest that chest x-ray, in addition to brain ultrasound, be routinely included in the evaluation of neonates whose mothers were involved in a motor vehicle accident during pregnancy, not excluding cases wherein the mother's injuries were negligible or inapparent and regardless of the time elapsed between accident and delivery.

Progressive liver calcifications in neonatal coxsackievirus infection.

Coxsackievirus group B can cause a severe systemic disease in the perinatal period. Severe manifestations like meningitis, encephalitis, hepatitis, and myocarditis have been previously reported. A case of a twin neonate infected by coxsackievirus group B is described, who developed progressive extensive hepatic calcifications demonstrated by ultrasound and computed tomography with follow-up. Hepatic calcifications in coxsackievirus infection have not been previously reported.