Cerebral and somatic NIRS-determined oxygenation in IUGR preterm infants during transition

Background: Fetal growth restriction (intra-uterine growth restriction [IUGR]) has a considerable impact on perinatal morbidity. Preterm IUGR infants are prone to impaired intestine function. Near-infrared spectroscopy (NIRS) has been used to monitor oxygenation status of the brain and of the intestine.

Patients and methods: We conducted a prospective case–control study at our NICU in 20 preterm infants of whom 10 infants complicated by compared with 10 non-IUGR preterm infants. Splanchnic and cerebral regional oximetry values were measured with NIRS. Three hours of consecutive recordings were performed in the first 24?h of life, T0, and during the transitional period, T1. The cerebral/splanchnic oxygenation ratio, CSOR, (cerebral regional saturations [rScO_2]/splanchnic regional saturations [rSsO₂]) was also calculated.

Results: Both in the IUGR and the non-IUGR infants, at T0 and T1 monitoring time-points, the rSO₂ values were higher in the cerebral district when compared to those of the splanchnic area. Comparison of the NIRS parameters between the IUGR and non-IUGR infants at T0 showed no difference in rScO₂, while rSsO₂ was significantly lower in the IUGR group. At T1, rScO₂ was significantly lower and rSsO₂ higher in the IUGR group.

Conclusions: Cerebral/splanchnic vascular adaptation of IUGR infants to the extra-uterine environment is characterized by a postnatal persistence of the brain sparing effect with reperfusion in the transitional period.     

Impact of transient period of metabolic adaptation on perinatal asphyxia in neonates with intrauterine growth retardation

Introduction: Temperature, glycemia and respiration make neonatal energy triangle (NET). In growth retardation (IUGR) neonates pathological metabolic adaptation exists in transient neonatal period.

Aim: The of this study was to examine the occurrence of pathological NET and check its impact on perinatal asphyxia during the transient period in IUGR neonates.

Material and methods: One hundred and fifty-nine neonates with IUGR were classified into – early preterm, late preterm and term neonates. By the presence of hypothermia, hypoglycemia and hypoxia in the first hour after birth neonates were classified into: group of pathological NET, group of unstable NET and group of stable NET. We analyzed distribution per body mass, gestational age, type of IUGR, gender and the frequency of perinatal asphyxia between the groups.

Results: The late preterm neonates were the most frequent in the group of pathological NET. Perinatal asphyxia was diagnosed in 52 (32.7%) neonates, with highest frequency in the group of pathological NET. Univariate binary logistic regression analysis showed that pathological NET in neonates with IUGR is significant predictor for perinatal asphyxia occurrence (OR?=?8.57; CI?=?4.05–18.12; p?R²?=?0.27).

Conclusion: Poor metabolic adaptation in neonates with IUGR in the first hour after birth is significant risk factor for the perinatal asphyxia.     

Congenital and perinatal cytomegalovirus lung infection

Abstract

Background: Cytomegalovirus (CMV) pneumonitis may be severe, even lethal, following congenital infection or in premature infants with perinatal infection.

Objective: To review the epidemiological, pathogenetic, clinical and therapeutic features of prenatal and perinatal CMV lung diseases.

Methods: Evaluation of all published papers listed on PubMed describing CMV pneumonitis in infants.

Results: CMV is frequent and severe in immunosuppressed infants but infrequent in full-term neonates and occurs more frequently after perinatal than after congenital infection, particularly in premature infants. In premature infants, CMV infection is often protracted and causes a diffuse interstitial pneumonitis leading to fibrosis and bronchopulmonary dysplasia (BPD). Congenital CMV infection should also be considered in newborns with severe acute respiratory distress syndrome and refractory respiratory failure with progression to early chronic lung disease. The association between breast milk-transmitted CMV and development of cystic lung disease and Wilson–Mikity syndrome has also been reported. Data on the efficacy of antiviral therapy for infants with respiratory CMV diseases are lacking and only anecdotal case reports are available.

Conclusions: Persistent CMV infection appears to cause a diffuse necrotizing pneumonitis with fibrosis leading to BPD, in both immunocompromised or preterm infants and, less frequently in immunocompetent infants. The role of antiviral therapy remains to be elucidated.     

Intervention for promoting breast milk use in neonatal intensive care unit: a pilot study

Abstract

Objective: The health benefits provided by breast milk are significant in preterm infants. Despite recommendations, rates of breastfeeding in preterm infants are lower than in term infants. The aim of this study was to evaluate the efficacy of a multidisciplinary intervention in promoting any breastfeeding in preterm infants at discharge.

Methods: A prospective non-randomized interventional cohort study was conducted. One hundred and twenty-two preterm infants constituted the historical group. A multidisciplinary intervention was performed including staff training and setting up and implementation of a written breastfeeding procedure.

Results: One hundred and ten preterm infants were enrolled in the intervention group. The percentage of infants fed human milk at discharge was 69 and 62 in the intervention group and in the historical group, respectively. The percentage change from any breastfeeding at full enteral feeding attainment to formula feeding at discharge was lower in the intervention group than in the historical group (?9 versus ?23). Belonging to the intervention group and having at least one stress factor during pregnancy were independently associated with any breast milk feeding at discharge.

Conclusions: The multidisciplinary intervention performed appears to be effective in promoting any breastfeeding in preterm infants at discharge.     

Placental histologic patterns and neonatal seizure,in preterm premature rupture of membrane

Objective: To investigate the relationship between placenta and perinatal outcomes, in preterm infants born to mothers with preterm premature rupture of fetal membrane (PPROM).

Methods: We report detailed histology of placentas and perinatal outcomes of infants from 79 PPROM pregnancies. Placental histologic pattern and adverse perinatal outcomes were assessed by logistic regression, adjusting for gestational age at birth, birth weight and interval from rupture of membrane to delivery.

Results: Mean gestational age at membrane rupture was 29.5?±?3.4 weeks. The incidence of histologic chorioamnionitis (HCA), fetal inflammatory response (FIR) and vascular thrombotic abnormalities in placental histologic examination were 63.3, 25.3 and 78.5%, respectively. Neonates with FIR showed significantly higher incidence of periventricular leukomalacia (PVL) (85% versus 59.3%, p?=?0.0364) at brain ultrasonography, than neonates without FIR, in univariate analysis, but not in logistic regression analysis. In logistic regression analysis, the odds ratio of low Apgar score at 1?min in the neonates with clinical chorioamnionitis was 5.009 (95% CI, 1.242–20.195). The odds ratio of neonatal seizure in the neonates with FIR and vascular thrombotic problem was 7.486 (95% CI, 1.617–34.653).

Conclusions: Our findings support the association between FIR with vascular thrombotic problem in placenta and neonatal seizure, in pregnancies with PPROM.     

Risk factors associated with respiratory disorders in late preterm infants

Objective: Late preterm infants are still high risk for respiratory problems. The aim of this study was to identify risk factors associated with respiratory problems in Japanese late preterm infants.

Methods: In this retrospective multicenter study, we included singleton late preterm deliveries at 34+^0/7–36+^6/7 weeks of gestation. We excluded cases with congenital anomalies. We defined neonatal respiratory disorders (NRD) as the combination of the need for mechanical ventilation or the use of nasal continuous positive airway pressure. We examined the perinatal risk factors associated with NRD.

Results: We included 683 late preterm infants. We found that 13.7%, 6.8% and 2.6% of the infants with NRD were born at 34, 35 and 36 weeks of gestation, respectively. In a multivariate logistic regression analysis adjusting for confounders, the gestational age (GA) at birth (adjusted odds ratio 0.40 per week [95% confidence interval, 0.25–0.61]), cesarean birth (4.18 [2.11–8.84]), and a low Apgar score (33.3 [9.93–121.3]) were independent risk factors associated with NRD.

Conclusions: An earlier GA, cesarean delivery, and a low Apgar score are independent risk factors associated with NRD in singleton late preterm infants. Patients with late preterm deliveries exhibiting these risk factors should be managed in the intensive delivery setting.     

Brain growth in preterm infants is affected by the degree of growth restriction at birth

Abstract

Objective: Documentation of examination of brain structural development by magnetic resonance imaging (MRI) beyond the neonatal period is scarce for both preterm and small for gestational age (SGA) infants.

Aim: To investigate structural brain development during infancy in preterm children born SGA by MRI.

Methods: A total of 205 preterm infants, 139 appropriate for gestational age (AGA) and 66 SGA, of which 33 had birth weight (BW)?<?3rd percentile and 33 had BW 3rd–10th percentile, were examined prospectively by brain MRI at the corrected age of 5 months. The total volume of the brain, ventricles and cerebellum, the area of vermis and corpus callosum, and the height of the pituitary, mesencephalon and pons were estimated on MRI.

Results: Brain volume was smaller in the SGA?<?3rd percentile infants, independent of other perinatal factors. Chronic lung disease was an independent predictor of low brain volume. Pituitary height was greater in SGA?<?3rd percentile than in AGA infants. The corpus callosum area was less in SGA?<?3rd percentile than in SGA of 3rd–10th percentile infants.

Conclusions: Preterm infants born SGA with BW?<?3rd percentile had differences in brain structural measurements at the corrected age of 5 months, compared with preterm AGA infants, which could have implications for their neurocognitive development.     

Asymmetric intrauterine growth restriction is a risk factor for respiratory inhibition after crying in infants

Objective: We investigated whether intrauterine growth restriction (IUGR) correlated with respiratory inhibition after crying (RIAC) and feeding hypoxemia.

Methods: We screened for RIAC among 1248 infants with a gestational age ≥36 weeks using our established method with cranial ultrasound, SpO₂ monitoring, and polygraphy. We classified the infants into three groups: symmetric IUGR, asymmetric IUGR, and control. We compared the perinatal factors with the incidence of RIAC and feeding hypoxemia among the three groups.

Results: Overall, 26 infants had symmetric IUGR, 143 infants had asymmetric IUGR, and 1079 infants were in the control group. RIAC was observed in 10 (6.9%) infants in the asymmetric IUGR group and in 37 (3.4%) infants in the control group. Feeding hypoxemia was observed in 15 (10.5%) infants in the asymmetric IUGR group and in 52 (4.8%) infants in the control group. The incidence of RIAC and feeding hypoxemia in the asymmetric IUGR group was significantly more than that in the control group. None of the infants with symmetric IUGR exhibited RIAC or feeding hypoxemia.

Conclusions: The results indicate that asymmetric IUGR is a risk factor for RIAC and feeding hypoxemia. These infants should be aggressively screened for RIAC.     

Improved outcomes of feeding low birth weight infants with predominantly raw human milk versus donor banked milk and formula

Objectives: To investigate the benefits of treating low birth weight infants predominantly with mother’s own raw milk and early initiation of breastfeeding (raw human milk/breast-fed infants), in comparison to feeding only with donor banked milk (until the third week of life) and afterwards a preterm formula until hospital discharge (donor banked/formula-fed infants).

Methods: One hundred and ninety-two predominantly raw human milk-fed infants (70% of raw and 30% of donor milk) were matched to 192 donor/formula-fed ones (on 1:1 ratio). Aggressive nutrition policy and targeted fortification of human milk were implemented in both groups.

Results: The two groups show similar demographic and perinatal characteristics. Predominantly raw milk-fed infants regained earlier their birth weight, suffered less episodes of feeding intolerance and presented a higher body length and head circumference at discharge (p?<?0.001). Those treated mainly with their mothers’ milk were able to initiate breastfeeding almost 2 weeks earlier compared to those fed with donor milk who achieved to be bottle-fed later on post-conceptual age (p?<?0.001). Infants being breastfed until the 8th month of life conducted less visits for a viral infection to a pediatrician compared to those in the other group (p?<?0.001).

Conclusions: Feeding predominantly with mother’s raw milk seems to result in optimal neonatal outcomes.     

Plasma copeptin may not be a sensitive marker of perinatal stress in healthy full-term growth-restricted fetuses

Objective: Intrauterine-growth-restriction-(IUGR) is associated with chronic fetal stress, as well as a phase of enhanced fetal/early postnatal insulin sensitivity, followed by a later emergence of insulin resistance. We aimed to prospectively investigate concentrations of copeptin, a sensitive marker of stress and insulin resistance, in IUGR versus appropriate-for-gestational-age-(AGA) fetuses.

Methods: Cord blood copeptin concentrations were determined by ELISA in well-defined, non-distressed at birth, asymmetric IUGR (n?=?30) and AGA (n?=?20) full-term pregnancies. Doppler studies were indicative of placental insufficiency.

Results: Cord blood copeptin concentrations were similar in IUGR cases and AGA controls, after controlling for delivery mode. Copeptin concentrations were markedly elevated in vaginally delivered fetuses (p?=?0.001). No association was recorded between fetal copeptin concentrations and maternal age, parity, gestational age, or fetal gender.

Conclusions: Cord blood copeptin concentrations are probably not affected by IUGR at term, in the absence of fetal distress, possibly due to a balance between copeptin up-regulation by chronic fetal stress, on one hand, and copeptin down-regulation in the presence of increased insulin sensitivity, on the other hand; thus, copeptin may not be a sensitive marker of chronic perinatal stress in healthy asymmetric IUGR infants. Cord blood copeptin seems to primarily reflect perinatal stress associated with delivery mode.     

Serum levels and ApaI polymorphism of insulin-like growth factor 2 on intrauterine growth restriction infants

Purpose: The aim of our study was to evaluate the IGF2 and IGF2R plasmatic level and IGF2-ApaI polymorphism on infants with intrauterine growth restriction (IUGR).

Materials and methods: A transversal study was conducted at the Neonatology Ward of the Gynecology Clinic I, Emergency Hospital Cluj-Napoca on neonates with IUGR who were discharged during June 2014 and June 2015. The serum levels of IGF2 and IGF2R were obtained by using ELISA method and IGF2-ApaI polymorphism by taking PCR-RFLP analysis.

Results: Forty infants with IUGR and 21 infants of appropriate gestational age (AGA) were evaluated. The serum levels of IGF2 proved higher on the A/G genotype when the IUGR group was compared with AGA (p value?=?.048). The G allele proved significantly more frequent in both the IUGR and the AGA group compared with the A allele (p?p value?>?.3). The A/G genotype proved significantly more frequent on term infants compared with preterm infants (p value?=?.039).

Conclusions: The infant with IUGR has a higher serum level of IGF2 if has A/G IGF2-ApaI genotype and higher values of IGF2R if it has the A/A genotype.     

Adverse perinatal outcomes after the February 27th 2010 Chilean earthquake

Objective: To investigate whether the February 27th earthquake exposition was associated to adverse perinatal outcomes in Chilean pregnant women.Methods: We analyzed all deliveries occurred in 2009 (n = 3,609) and 2010 (n = 3,279) in a reference hospital in the area of the earthquake. Furthermore, we investigated pregnant women who gave birth between March 1st and December 31st 2010 (n = 2,553) and we classified them according to timing of exposition.Results: We found a 9% reduction in birth rate, but an increase in the rate of early preterm deliveries (<34 weeks), premature rupture of membranes (PROM), macrosomia, small for gestational age, and intrauterine growth restriction (IUGR) after the earthquake, in contrast to the previous year. Women exposed to the earthquake during her first trimester delivered smaller newborns (3,340 ± 712 g v/s 3,426 ± 576 g respectively, p = 0.007) and were more likely diagnosed with early preterm delivery, preterm delivery (<37 weeks) and PROM but were less likely diagnosed with IUGR and late delivery (42 weeks, p < 0.05) compared to those exposed at third trimester. Accordingly, IUGR and preterm deliveries presented elevated healthcare costs.Conclusion: Natural disasters such as earthquakes are associated to adverse perinatal outcomes that impact negatively the entire maternal-neonatal healthcare system.     

Outcome of breastfed infants following post-partum methylergonovine treatment

Objective: To evaluate maternal and breastfed infant’s outcome following post-partum maternal use of methylergonovine.

Methods: A prospective, controlled observational study design was used. Mothers who contacted Beilinson Teratology Information Service (BELTIS) were followed by phone interview. Data on lactation, neonatal symptoms and outcomes at the age of 1–3 years were obtained. Mothers’ breastfeeding while treated with methylergonovine and their infants were compared to a matched control group of breastfeeding mothers using a drug known to be safe during lactation (amoxicillin).

Results: Follow-up was obtained for 38 of 42 women (90.5%). Of whom, six stopped breastfeeding because of concerns regarding drug treatment and three refused to participate. The remaining 29 women and infant pairs were compared to a control group of 58 women and their infants. Comparison showed no effect of methylergonovine on lactation and similarly showed no difference in rate of neonatal complications (p?=?1). At time of follow-up there were no differences in growth or in adverse neurodevelopment outcomes (p?=?0.26).

Conclusions: No increase in adverse long-term outcomes was found in infants exposed to methylergonovine through breastfeeding. Our data in conjunction with previous estimates of very low drug exposure support continuation of breastfeeding in women requiring treatment with methylergonovine.     

Waiting for postterm in healthy women,is it an accident waiting to happen?

Abstract

Objective: To establish whether postterm pregnancies are associated with adverse perinatal outcomes in a linear fashion.

Study design: A retrospective cohort study investigating perinatal outcomes in singleton term (≥37 weeks gestation) and postterm pregnancies was conducted. Deliveries occurred between the years 1988 and 2010. Parturients were classified into three groups according to their gestational age: 37–39?+?6, 40–41?+?6 and over 42 weeks’ gestation (postterm). Statistical analysis included multiple logistic regression model to control for possible confounders.

Results: Out of 202?462 deliveries, meeting the inclusion criteria, during the study period, 47.7% occurred at 37–39?+?6 weeks, 47.4% occurred at 40–41?+?6 weeks and 4.9% were postterm. Fertility treatments, diabetes mellitus, hypertensive disorders, intrauterine growth restriction (IUGR) and premature rupture of membranes (PROM) were less likely to be associated with postterm pregnancies. However, postterm was found as a significant risk factor for labor complications and adverse perinatal outcome including perinatal mortality. Using a multivariable logistic regression model, controlling for confounders such as maternal age and macrosomia, postterm was found to be an independent risk factor for perinatal mortality (adjusted OR?=?1.5; 95% CI?=?1.20–2.0; p?<?0.001).

Conclusion: Although postterm pregnancies were less likely to be associated with obstetrical risk factors and complications such as fertility treatments, diabetes mellitus, hypertensive disorders, IUGR and PROM, postterm is an independent risk factor for perinatal mortality.     

Clinical factors that enhance morbidity and mortality in intrauterine growth restricted foetuses delivered between 23 and 30 weeks of gestation

Objective.?To find clinical factors that are associated with poor outcome (death and brain damage) in premature intrauterine growth restricted (IUGR) infants.

Methods.?A retrospective study was performed to compare the incidence of poor outcome between 45 IUGR and 203 appropriate-for-gestational-age (AGA) infants born before 30 weeks of gestation. Foetal tests included foetal heart rate monitoring, Doppler flow, amniotic fluid, and head circumference. Growth for gestational age was categorised as 10th through 3rd, third through first, and below first percentiles.

Results.?In infants below 25 weeks of gestation, the incidence of poor outcome was not different between IUGR and AGA. In infants between 25 and 30 weeks of gestation, the incidence of poor outcome was significantly increased in IUGR compared with AGA (12/40, 30% versus 11/136, 8.1%, p?<?0.01). Univariate analysis showed that abnormality in foetal heart rate monitoring [odds ratio (OR) 8.3, 95% confidence interval (CI) 1.58–43.6], head circumference (OR 7.0, 95%CI 1.42–34.4), and Doppler flow (OR 10.9, 95%CI 1.83–64.6) was significantly associated with poor outcome in IUGR infants. However, no foetal tests were significantly associated with poor outcome after adjusting for the 3-grade birthweight percentiles.

Conclusions.?Immaturity outweighs clinical problem associated with IUGR in infants below 25 weeks of gestation. Between 25 and 30 weeks of gestation, there was a growth threshold below third percentile where foetal tests were not significant predictors of poor outcome, but that was primarily determined by birthweight.     

A new formula for premature infants: effects on growth and nutritional status

Objective: Nutritional management influences immediate survival as well as subsequent growth and development of low birth weight and very low birth weight infants. Preterm infant formula (PTF) is used when there is an inadequate supply of mother’s milk or when the mother is unable to breastfeed and donor breast milk is unavailable. The purpose of this prospective multicenter study was to evaluate short-term effects on nutritional status (auxological and biochemical parameters) in a population of premature infants who received a preterm infant formula.

Methods: Ninety-seven preterm infants with a birth weight between 500?g and 2000?g and a gestational age of 25–34 weeks postmenstrual age were randomly assigned to received a new preterm infant formula (Nutribèn Pre), and their nutritional status were compared to 75 fortified human milk (FHM) fed infants.

Results: No significant differences were observed between FHM and Nutribèn Pre fed infants in terms of growth, feeding tolerance and biochemical profiles.

Conclusion: Nutribèn Pre is a valid, effective and safe alternative for the nutrition of preterm infants.     

A metabolomic study of preterm and term human and formula milk by proton MRS analysis: preliminary results

Abstract

Objective: To investigate changes in global metabolic profile between: 1 – breast milk and formula milk, 2 – breast milk from mothers delivering at different gestational age (GA) collected within one week from delivery, and then week by week until term equivalent age.

Methods: Proton magnetic resonance spectroscopy (MRS) was used to analyze the water-soluble and lipid fractions extracted from 50 milk samples, 46 human milk at different GA, from 23 weeks of gestation until term equivalent age and four different formula milks.

Results: The formula milk for premature infants was the most similar to breast milk of preterm babies. Breast milk showed higher lactose concentrations than formula milk, that conversely presented higher galactose 1-phosphate and maltose concentrations. Mother’s milk of very preterm babies (23–25?wks of GA) showed a different metabolic profile from preterm infants ≥29?wks of GA with a subsequent trend to similarity around the 30th week of post-natal age. Breast milk from preterm infants of 29–34?wks, collected up to 40?wks of post-natal age showed a temporal change over the first three weeks of lactation, approaching to zero with the achievement of term age.

Conclusions: Metabolome is a promising tool to study human and artificial milk global metabolic profile.     

Oligohydramnios and growth restriction do not portend worse prognosis in gastroschisis pregnancies

Objectives: Gastroschisis is a common abdominal wall defect. While most neonates have an excellent prognosis, complications do occur. Several risk factors for adverse neonatal outcomes have been identified, however, the impact of intrauterine growth restriction (IUGR) and oligohydramnios on neonatal morbidity and mortality has not been fully elucidated.

Methods: In this retrospective cohort study of pregnancies complicated by gastroschisis at two tertiary-care centers during an eight-year period, maternal, fetal and neonatal data were analyzed to estimate the impact of IUGR and oligohydramnios upon neonatal outcomes. Adverse outcomes were defined as five-minute Apgar score <7, umbilical cord pH <7.12, neonatal sepsis, prolonged ventilator support, prolonged total parenteral nutrition, extended NICU stay, death and a composite of the above.

Results: Among the 179 cases of gastroschisis, there were no differences in maternal demographics between cases with and without IUGR or oligohydramnios. Fetuses with oligohydramnios demonstrated a trend toward lower birthweight (p?=?0.06). Small for gestational age infants showed a trend toward prolonged ventilator support (p?=?0.06). Oligohydramnios and IUGR were otherwise not associated with adverse neonatal outcomes.

Conclusions: While risk factors for adverse neonatal outcomes have been identified in pregnancies complicated by gastroschisis, IUGR and oligohydramnios do not appear to be among them.     

Long-term outcome at age 7–10 years after extreme prematurity – a prospective,two centre cohort study of children born before 25 completed weeks of gestation (1999–2003)

Abstract

Objective: We aimed to determine the long-term neurodevelopmental outcome in extremely preterm infants of 22–23 completed weeks’ gestation as compared to infants of 24 weeks with immediate postnatal life support born in two German tertiary perinatal centres between 1999 and 2003.

Methods: Children were assessed for cognitive and neurological outcomes at the age of 7–10 years. The test battery included a neurological examination, the Wechsler Intelligence Scale for children (WISC-IV) and the Frostigs Developmental Test of Visual Perception (DTVP-2). Gross motor function was classified according to the GMFCS and functional activity was assessed with the Lincoln Oseretzky Motor Development Scale (LOS KF 18).

Results: Outcome data were available for 79/105 children. 75.9% of the entire study cohort showed no or mild impairment. There was no difference seen between the two gestational age groups. Risk factors for moderate or severe impairment were an intracerebral haemorrhage >II° and/or periventricular leukomalacia or a retinopathy of prematurity >II°. Neither the gestational age (GA) nor the birth weight was associated with long-term outcome.

Conclusions: Gestational age was not a predictor for long-term impairment of preterm infants born <25 completed weeks’ GA. Other prognostic factors should be taken into account for counselling in the grey zone of viability.