Dror Mandel

Circadian variations in fat content of expressed breast milk from mothers of preterm infants.

Background:Little is known about circadian variations of the fat content in expressed human milk by mothers of preterm infants. Objective: To test the hypothesis that the fat content of expressed preterm human milk is higher in samples expressed in the evening (i.e. after 3 daily meals) than in the morning (after a night-long fast). Methods: We collected samples of expressed human milk obtained from 39 mothers of hospitalized growing preterm infants aged 7–14 days, with a gestational age at birth ranging from 26 to 33 weeks, who routinely expressed all their milk every 3 hours, during the day time, just before bed time, and as soon as they woke up, using a commercial breast pump (Medela AG, Baar, Switzerland). One sample was obtained from the first morning expression (between 0600 and 0900) and the second from the evening expression (between 2100 and 2400). The entire quantity of expressed milk was collected, mixed and measured in a capillary tube after centrifugation at 9000 rpm for 5 minutes. Creamatocrits (CMT) were performed in duplicates. Each sample was read independently by 2 investigators who were not aware of the origin and time of sampling and the results were averaged. Results are expressed as mean ± SD, and analyses were by paired t-test and regression analysis. Results: CMT was significantly higher in evening than in morning samples (7.9 ± 2.9% vs. 6.6 ± 2.8%, P = 0.005). Neither CMT nor the morning-evening difference in CMT correlated with gestational age or birthweight. The morning CMT correlated significantly with the evening CMT (P < 0.001). Conclusions: There are significant circadian variations in the CMT of expressed preterm human milk. We speculate that if higher caloric content of expressed human milk is needed in a specific preterm infant, evening sample, if available, should be used preferentially.

Loeys-Dietz Syndrome in Pregnancy: A Case Description and Report of a Novel Mutation

Loeys-Dietz syndrome is a syndrome caused by heterozygous mutations in the genes encoding type 1 or 2 transforming growth factor-β receptor (TGF-β-R1/2). The obstetrical manifestations are risk of rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period, and damage to the vagina, perineum and the colon. We describe, for the first time, a new TGF-β-R2 gene mutation in a family with several individuals who either had aortic rupture and dissection, sudden death or aortic root dilatation. The pregnancy was followed up and the baby was successfully delivered by a cesarean section at 34 weeks of gestation. The mother’s recovery was uneventful and the baby was negative for the mutation on postnatal molecular testing. With appropriate supervision and early delivery by cesarean section, women with Loeys-Dietz syndrome can tolerate pregnancy and delivery without any adverse effect.

Bone ultrasound velocity of infants born small for gestational age

BACKGROUNDnQuantitative ultrasound is increasingly used to assess bone status. Bone speed of sound (SOS), a biophysical property of bone, has been used to predict bone breakability. While decreased bone mineral content and delayed epiphyseal growth have been reported in small for gestational age (SGA) infants, there are no data on bone SOS in this group of infants.nnnOBJECTIVEnTo test the hypothesis that SGA infants have lower bone SOS than appropriate for gestational age (AGA) infants.nnnMETHODSnBone SOS was measured within the first 96 hours of life at the right tibial midshaft in 22 singleton SGA infants. We compared these data with data obtained in 73 AGA controls. We used the Omnisense instrument which measures axially transmitted SOS. Infants ranged in gestational age (GA) from 25 to 42 weeks and in birth weight (BW) from 500 to 2,585 g. Statistical analyses included paired t-tests between the actual value obtained in every child and the theoretical, computed average normal value for GA, BW, or knee-sole length (KSL) based on our curves for AGA singletons. A p value < 0.05 was considered significant.nnnRESULTSnBone SOS measured in SGA infants was higher than the predicted computed average SOS of AGA singletons with significant differences in all of the parameters studied.nnnCONCLUSIONSnContrary to our hypothesis, SGA infants have higher bone SOS than AGA controls. Since bone mineral density is reported to be low in these infants, we speculate that intrauterine growth restriction may affect bone mineral density and bone protein matrix in opposite directions.

Conclusiveness of the Cochrane Neonatal Reviews: A systematic analysis

Aim: To assess the conclusiveness of the Cochrane Neonatal Reviews (CNRs). We tested the hypotheses that: 1) the majority of the reviews is inconclusive; 2) the majority of reviews recognizes the need for further studies; 3) the ability to reach a conclusion is dependent upon both the number of studies and the number of patients. We also aimed to determine whether the conclusiveness of the CNRs was affected by time.

Electroencephalographic Characteristics in Preterm Infants Born with Intrauterine Growth Restriction

OBJECTIVEnTo determine the impact of fetal growth on postnatal amplitude-integrated electroencephalography (aEEG) and power spectrum electroencephalography (EEG) data in preterm infants born with intrauterine growth restriction (IUGR).nnnSTUDY DESIGNnWe defined IUGR as birth weight <10th percentile, and control as birth weight appropriate for gestational age (GA). We performed single-channel (C3-C4) EEG during the first 48 hours of life and measured the upper and lower margins of the aEEG trace width. EEG readings were analyzed by spectral analysis, and the relative power of the frequency bands was calculated. The Lacey Assessment of the Preterm Infant was administered before discharge.nnnRESULTSnWe enrolled 14 infants with IUGR (mean GA, 34.3 ± 1.8 weeks; mean birth weight 1486 ± 304 g) and 16 appropriate for GA controls (mean GA, 33.7 ± 2 weeks; mean birth weight, 1978 ± 488 g). There were no significant between-group differences in perinatal complications. The mean aEEG trace width was 20.8 ± 1.4 μv in the infants with IUGR versus 17.3 ± 1.6 μv in controls (P < .001). The infants with IUGR also had significantly greater delta frequency activity and decreased theta, alpha, and beta frequency activities compared with controls. Delta frequency activity decreased with increasing GA (r = -0.8; P = .001 for infants with IUGR and r = -0.9; P < .001 for controls). The Lacey Assessment of the Preterm Infant developmental score was significantly lower in the infants with IUGR (P < .02) and was correlated with aEEG trace width (r = -0.6; P = .002) and with delta activity (r = -0.5; P = .02).nnnCONCLUSIONnPreterm infants with IUGR have delayed EEG maturation associated with delayed neuromotor development. The predictive value of these alterations regarding developmental deficits associated with IUGR remains undetermined, however.

Neonatal Nucleated Red Blood Cells in Infants of Overweight and Obese Mothers

Objective: The perinatal outcome of the infant of obese mother is adversely affected and in theory, may involve fetal hypoxia. We hypothesized that an index of fetal hypoxia, the neonatal nucleated red blood cell (NRBC) count, is elevated in infants of overweight and obese mothers. Study Design: Absolute NRBC counts taken during the first 12 hours of life in 41 infants of overweight and obese mothers were compared to 28 controls. Results: Maternal body mass index and infant birthweight were significantly higher in the overweight and obese group (P < 0.01). Hematocrit, corrected white blood cell and lymphocyte counts did not differ between groups. The absolute NRBC count was higher (P = 0.01), and the platelet count lower (P = 0.05) in infants of overweight and obese mothers than in controls. In stepwise regression analysis, the absolute NRBC count in infants of overweight and obese mothers remained significantly higher even after taking into account birthweight or gestational age and Apgar scores (P < 0.02). Conclusion: Infants of overweight and obese mothers have increased nucleated red blood cells at birth compared with controls. We speculate that even apparently healthy fetuses of overweight and obese mothers are exposed to a subtle hypoxemic environment.

Human milk fatty acids composition is affected by maternal age.

Abstract Human colostrums and transition milk were collected from women under the age of 37 years and women aged 37 years and older. Transition milk of the younger group had lower fat content and 10-fold higher concentrations of omega 6u2009FA, eicosadecanoic, and arachdonic acids. Gestational age affected the colostrum concentration of total fat and omega 3 and omega 6u2009FA composition only in the older group. We concluded that age may be a factor in the FA composition of human milk. This should be taken into account when planning diets for pregnant women of different ages.

The influence of prolonged preterm premature rupture of the membranes on neonatal outcome of the presenting and non-presenting twin.

OBJECTIVEnTo compare the neonatal outcome in twin gestations complicated by prolonged preterm premature rupture of membranes (PPROM).nnnSTUDY DESIGNnBetween the years 2000 and 2010 we identified 48 women with twin pregnancies who were diagnosed as having PPROM and a latency period to delivery >24h. We compared the neonatal morbidity and mortality between the presenting and non-presenting twins, assuming that the rupture occurred in the lower sac. Importantly, in 30 women we were able to identify the location of the ruptured sac by ultrasound examination demonstrating oligohydramnion. In these 30 cases, neonatal outcome of fetuses in the ruptured sac and those in the intact sac were compared.nnnRESULTSnThe median gestational age was 31 weeks (range 28-33) with a median latency period between PPROM and delivery of 9 days (range 1-18). Of the identified ruptures 90% (27/30) occurred in the lower sac (presenting twin). There was no significant difference between the presenting and non-presenting twin in terms of neonatal morbidity and mortality. Moreover, no difference was found when fetuses with ruptured sac were compared to those with intact membrane sac. Importantly, the outcomes were not affected by the length of the latency period.nnnCONCLUSIONnThe current study results demonstrated that the outcome of fetuses exposed to prolonged preterm rupture of membranes is similar to that of fetuses with intact membranes. Our data suggest that rupture of membranes per se did not cause any deleterious clinical manifestations or lead to clinical discordant inflammation and poor neonatal outcome, supporting a conservative management of twin pregnancies with PPROM.

The Use of Multinutrient Human Milk Fortifiers in Preterm Infants: A Systematic Review of Unanswered Questions

There is evidence that multinutrient fortification of human milk increases in-hospital growth of preterm infants, but fortification has not been shown to improve long-term growth and neurodevelopmental outcome. We aimed to ascertain whether randomized controlled trials have determined the effect of early versus late introduction of fortifiers on growth and/or other outcomes, and have compared the efficacy/adverse effects of human milk-based versus cow milk-based fortifiers. We conclude that there is little evidence that early introduction of human milk fortification affects important outcomes, and limited evidence that a bovine fortifier places the infant at a higher risk of NEC.

Pulmonary hemorrhage due to Coxsackievirus B infection—A call to raise suspicion of this important complication as an end-stage of enterovirus sepsis in preterm twin neonates

BACKGROUNDnPrematurity is an important risk factor for the fulminate form of neonatal enteroviral infection. Pulmonary hemorrhage is a morbid complication that should be anticipated and managed aggressively due to its fatal outcome.nnnOBJECTIVEnTo emphasize the significance of pulmonary hemorrhage as a complication of severe enterovirus infection in preterm neonates.nnnSTUDY DESIGNnThis report is a description of the clinical history, medical management and clinical outcomes of two pairs of preterm twin newborns (30 weeks and 36 weeks) with fulminant infection due to Coxsackievirus B (CBV) infection.nnnRESULTSnMaternal fever was reported in both deliveries and it was a factor in the decision for urgent cesarean section of the 30-week twins. Three of the four infants failed to survive. Their clinical course involved multiple organ system failure complicated with profound disseminated intravascular coagulopathy and pulmonary hemorrhage. Pulmonary bleeding leading to hypovolemic shock and respiratory failure was the direct cause of death in two cases.nnnCONCLUSIONSnThis small series of preterm neonates with the diagnosis of CBV sepsis highlights the importance of correct diagnosis of maternal enterovirus infection in order to extend pregnancy and allow the fetus time to passively acquire protective antibodies. This report emphasizes the morbid complication of pulmonary hemorrhage as a result of enterovirus infection that should be anticipated and managed aggressively due to its potentially fatal outcome. Moreover, evaluation and observation of the asymptomatic twin is recommended in order to detect early signs of infection and deterioration in that sibling as well.