Serial measurements of C-reactive protein and interleukin-6 in the immediate postnatal period: reference intervals and analysis of maternal and perinatal confounders

BACKGROUND: There is a wide range of reported sensitivities and specificities for C-reactive protein (CRP) and interleukin-6 (IL-6) in the detection of early-onset neonatal infection. This prompted us to assess reference intervals for CRP and IL-6 during the 48-h period immediately after birth and to identify maternal and perinatal factors that may affect them. METHODS: CRP and IL-6 values were prospectively obtained for 148 healthy babies (113 term, 35 near-term) at birth and at 24 and 48 h of life, and from their mothers at delivery. RESULTS: Upper reference limits for CRP at each neonatal age were established. At birth, CRP was significantly lower than at 24 and 48 h of life. Rupture of membranes > or =18 h, perinatal distress, and gestational hypertension significantly affected the neonatal CRP dynamics, but at specific ages. There was no correlation between CRP concentrations in mothers and their offspring at birth. The IL-6 values observed in the delivering mothers and in their babies at all three neonatal ages were negatively associated with gestational age. In the immediate postnatal period, IL-6 dynamics for term babies were significantly different from those for near-term babies. Maternal IL-6 concentrations correlated with babies' IL-6 concentrations only for term deliveries. Apgar score had a significant effect on babies' IL-6 values at birth. CONCLUSIONS: The patterns of CRP and IL-6 responses in the healthy neonate should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis.     

新生儿出生早期血清降钙素原浓度变化规律及其影响因素分析

目的探讨新生儿出生早期血清降钙素原(PCT)变化规律及常见围产因素对PCT水平的影响。方法分析2012年1月至2014年12月该院收治的无感染健康新生儿470例,其中足月儿240例,早产儿230例,分析其出生一周内血清PCT水平,采用多元线性回归分析胎龄等常见围产因素对PCT水平的影响。结果足月儿及早产儿PCT水平在出生时极低,出生后12h内均略上升,并分别于出生后≥12~24h及≥24~48h达峰值,随后均逐步下降,最后两者分别在出生后约72h后及96h后降至正常婴儿水平。多元回归分析提示早产儿的PCT水平与样本检测时间(出生日龄)及其胎龄大小相关,足月儿PCT水平仅与出生日龄相关。结论足月儿及早产儿在出生早期PCT生理波动规律有所不同,且早产儿胎龄与PCT水平相关,该发现对于新生儿早发细菌感染的诊断与鉴别诊断、指导临床合理使用抗菌药物有重要临床意义。     

C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period

BackgroundThere is still no study evaluating the influence of gestational age (GA) per se on C reactive protein (CRP) and procalcitonin (PCT) reference intervals. We therefore investigated how length of gestation, age (hours), and prenatal and perinatal variables might influence the levels of CRP and PCT. We also determined 95% age-specific reference intervals for CRP and PCT in healthy preterm and term babies during the early neonatal period.MethodsOne blood sample (one observation per neonate) was taken for CRP and PCT from each newborn between birth and the first 4 (for term), or 5 days (for preterm newborns) of life by using a high-sensitive CRP and PCT assays.ResultsIndependently of gender and sampling time, GA had a significantly positive effect on CRP, and a significantly negative effect on PCT. Compared with healthy term babies, healthy preterm babies had a lower and shorter CRP response, and, conversely, an earlier, higher, and longer PCT response. CRP reference intervals were affected by a number of pro-inflammatory risk factors.ConclusionsAge- and GA-specific reference ranges for both CRP and PCT should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis.     

Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia

BACKGROUND: A correlation between elevation of pro-inflammatory cytokines and white matter injury or abnormal neurologic outcome has been established in the preterm infant. In the full-term neonate, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. Our aims were to investigate if serum interleukin-6 concentrations in delivering mothers and their offspring at birth are associated with perinatal asphyxia, and to examine the relation of interleukin-6 levels to the severity of hypoxic-ischemic encephalopathy and to the neurological outcome. DESIGN AND METHODS: Serum interleukin-6 levels were measured at birth, 24 and 48 h of life in 50 consecutive term uninfected newborns with perinatal asphyxia and 113 randomly selected healthy term newborns, and at delivery in their mothers. RESULTS: The median cord interleukin-6 concentrations in the infants who developed hypoxic-ischemic encephalopathy was 376-fold as high as the values in the normal infants (P < 0.0001) and 5.5-fold as high as those in the infants with asphyxia who did not develop hypoxic-ischemic encephalopathy (P < 0.05). There was also a significant relationship between interleukin-6 and the degree of hypoxic-ischemic encephalopathy, and between interleukin-6 and neurodevelopmental outcome at 2 years of age. Regardless of outcome, in the asphyxiated infants the interleukin-6 values were significantly lower at both 24 and 48 h of life than at birth, with a significant decline from 24 to 48 h of life. Among mothers of the asphyxiated neonates, there were no significant differences in interleukin-6 concentrations between those delivering neonates with and without hypoxic-ischemic encephalopathy. CONCLUSIONS: Measurement of IL-6 concentrations in the umbilical cord of neonates with perinatal asphyxia may be useful to identify early, and in a relatively simple way, those who are most likely to have subsequent brain injury and adverse outcome.     

C-reactive protein,interleukin-6, and procalcitonin in the immediate postnatal period: influence of illness severity,risk status,antenatal and perinatal complications,and infection

BACKGROUND: Studies of the diagnostic accuracy of most laboratory tests for early-onset neonatal sepsis have yielded variable results. We investigated whether some of this variation might be attributable to differences in population baseline severity and risk status as well as to specific ante- and perinatal variables, independent of the presence of neonatal infection. METHODS: The Score for Neonatal Acute Physiology (SNAP) was used to define illness severity, with SNAP Perinatal Extension (SNAP-PE) used to define the combined physiologic and perinatal mortality risk. A total of 134 ill newborns (19 with early-onset infection and 115 with no infection) were available for simultaneous analysis of the association of SNAP, SNAP-PE, and maternal and perinatal variables with C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) concentrations at birth and at 24 and 48 h of life. RESULTS: Early-onset neonatal infection was associated with significant increases in CRP, IL-6, and PCT concentrations at all three time points, independent of illness severity. However, among babies without infection, higher SNAP and SNAP-PE scores were associated with higher IL-6 concentrations at birth. Certain maternal or perinatal variables altered IL-6 and PCT values in the infected as well as in the uninfected neonates. However, if different cutoff points were used at any of the three neonatal ages, PCT sensitivity and specificity were greater than those of CRP or IL-6. CONCLUSIONS: Illness severity and risk status are unlikely to interfere with the use of CRP and PCT for detection of early-onset neonatal sepsis. In contrast, the diagnostic value of IL-6 at birth may be altered by physiologic severity and risk indexes. The reliability of CRP, IL-6, and PCT for the diagnosis of early-onset neonatal infection requires specific cutoff values for each evaluation time point over the first 48 h of life.     

出生24 h内外周血炎性标志物在NEOS中的水平及NEOS病原菌分布

目的分析外周血炎性标志物在新生儿早发型败血症(NEOS)患儿出生24 h内的水平,并调查该院NEOS病原菌分布。方法回顾性分析该院2014年7月至2017年12月收治的451例新生儿,分为NEOS组(363例)和对照组(88例),比较两组一般资料,围生期影响因素,外周血炎性标志物超敏C反应蛋白(hs-CRP)、血清降钙素原(PCT)、白细胞计数(WBC)及中性粒细胞/淋巴细胞比值(NLR)水平,评估新生儿出生24 h内外周血炎性标志物对NEOS的诊断效能。结果两组的胎龄、体质量、低出生体质量患儿比例、住院时间、5 min Apgar评分比较,差异有统计学意义(P<0.05)。两组患儿母亲在孕次、产次、胎膜早破、产前发热、羊水异常方面比较,差异无统计学意义(P>0.05),而生产方式差异有统计学意义(P<0.05)。NEOS患儿病原菌培养出革兰阳性菌177例,以凝固酶阴性葡萄球菌为主;革兰阴性菌168例,以大肠埃希菌和肺炎克雷伯菌为主。血清PCT对NEOS具有较高的诊断效能。动态分析两组血清PCT变化趋势,NEOS组24~<48 h达到高峰,72 h后下降,而对照组在24 h内达到峰值。结论引起NEOS的革兰阳性菌以凝固酶阴性葡萄球菌为主,革兰阴性菌以大肠埃希菌和肺炎克雷伯菌为主。血清PCT水平在出生24 h内即可预测NEOS,动态监测血清PCT水平有助于早期诊断NEOS及监测疗效。     

新生儿高胆红素血症围产期危险因素分析

目的 探讨新生儿高胆红素血症的围产期因素及其危险因素.方法 回顾分析住院治疗的1983 例新生儿临床资料,探讨高胆红素血症围产期因素,并采用多因素Logistic 回归方法分析新生儿胆红素血症围产期的危险因素.结果 新生儿高胆红素血症与新生儿性别、胎次、产妇年龄和分娩方式无明显相关性,而与新生儿胎龄、出生时体重、围产并发症、开始喂奶时间和胎粪排出时间相关;Logistic 回归分析以高胆红素血症为应变量、危险因素为待选变量,结果显示胎龄<37 周、低出生体重、围产窒息、宫内窘迫、感染、出血、开始喂奶时间＞24h 和胎粪排出时间＞24h 为新生儿高胆红素血症围产期危险因素(P<0.05 ).结论 新生儿高胆红素血症围产期危险因素为胎龄<37 周、低出生体重、围产窒息、宫内窘迫、感染、出血、开时喂奶时间＞24h 和胎粪排出时间＞24h.     

Early growth in offspring of diabetic mothers

OBJECTIVE: By age 5 years, offspring of diabetic mothers (ODMs) are heavier and have altered glucose metabolism compared with offspring of mothers without diabetes (non-DMs). This study evaluates the growth pattern of ODMs before the age of 5 years. RESEARCH DESIGN AND METHODS: Anthropometric measures (z scores) from birth, 1.5 years, and 7.7 years in Pima Indian children were compared by maternal diabetes status. RESULTS: After adjustment for earlier gestational age at delivery (37.8 vs. 39.3 weeks, P < 0.01), ODMs were heavier at birth (z score birth weight 0.49 vs. -0.04, P < 0.01) than non-DMs. At age 1.5 years, ODMs were shorter than the non-DMs (z score = -0.24 vs. 0.12, P < 0.01) but their weight and relative weight (RW; weight adjusted for age, sex, and length or height) were similar. From birth to 1.5 years, ODMs showed significant "catch down" of weight compared with non-DMs (change in weight z score from birth to 1.5 years of ODMs and non-DMs was -0.56 and 0.12, respectively, P < 0.01). By age 7.7 years, ODMs were heavier (weight z score 0.89 vs. -0.07, P < 0.01) but had similar height as non-DMs. Differences in glucose and insulin concentrations at age 7.7 years were dependent on RW. CONCLUSIONS: ODMs had a dramatically different growth pattern from that of non-DMs. Gestational age-adjusted birth weight was higher. During the first 1.5 postnatal years, the change in weight z score and attained height were reduced. Subsequently, height caught up to that of non-DMs, while weight gain greatly exceeded that of non-DMs.     

Maternal zinc and intrauterine growth retardation

The levels of zinc in plasma, erythrocytes, polymorphonuclear (PMN) and mononuclear (MN) white cells were measured after delivery in women giving birth to appropriate-for-gestational-age (AGA) babies (group I mothers), or small-for-gestational-age (SGA) babies (group II mothers) and in non-pregnant controls. Mean maternal plasma zinc and albumin levels 24-48 h after delivery were lower than in controls, but PMN and MN zinc levels were unchanged. PMN zinc levels were lower than those of MN cells. PMN and MN zinc levels were significantly lower in group II mothers than in group I, irrespective of smoking habits. There were no racial differences in peripheral white cell zinc levels. PMN, and to a lesser degree MN, zinc levels were lower in smoking than in non-smoking mothers. Erythrocyte zinc did not correlate with other zinc measurements nor with the size of the babies. Fetal erythrocyte zinc levels were one-third of maternal levels. A combination of smoking and/or low PMN zinc levels selects 85% of mothers having small-for-gestational-age babies.     

Procalcitonin for the diagnosis of early-onset neonatal sepsis: a multilevel probabilistic approach

ObjectivesTo compare the accuracy of procalcitonin (PCT) in early-onset neonatal sepsis (EOS) using standard cut-off values and a multilevel probabilistic approach.Design and methodsA retrospective study of PCT was performed in 149 newborns at risk of EOS, including preterm or prolonged rupture of membranes, chorioamnionitis or maternal infection, GBS colonization and signs of fetal distress. PCT values were analysed according to time of assay, i.e. at birth and at 24 and 48 h. We estimated sensitivity, specificity, positive (LR+) and negative likelihood ratio (LR?), diagnostic odds ratio (DOR) and number needed to diagnose (NND) using traditional and optimal (derived from ROC analysis) PCT cut-off values.ResultsUsing optimal cut-off, the LR+, DOR and NND at birth were 10, 18.9 and 2.2, at 24 h they were 5.3, 11.2 and 2.1, and at 48 h they were 5.6, 18.1 and 1.7, respectively. The multilevel analysis generated three post-test probabilities for each time of assay. At 24 h post-test probabilities of EOS were 78% for PCT >90, 11% for PCT 10.1–90 and 3% for PCT <10.1 mg/L, respectively. Similar results were found in the other time points, with a wide range of intermediate PCT concentrations that did not change the post-test probability.ConclusionsThe multilevel probabilistic approach was more effective in assessing the diagnostic power of PCT in EOS, showing that a wide range of intermediate PCT values was not able to discriminate between presence and absence of infection.     

Impact of Prematurity on Perinatal Mortality and Morbidity

Severe prematurity is a prime factor causing perinatal mortality or morbidity. In Finland 1 % of babies are born before 32 completed weeks of pregnancy and 0.9 % are delivered with a birth weight of 1500 g or less. Since transport of a baby in utero is preferable to transporting a neonate, approximately 85 % of infants below 1000 g and 90 % of infants between 1000 to 1499 g are delivered in departments with facilities for neonatal intensive care. The rate of caesarean delivery is approximately 50 % in pregnancies between 26 and 28 weeks, while the overall caesarean section rate is 15 %. Deaths of low birth weight babies account for 66 % of the total perinatal mortality and those of very low birth weight babies 46 %. Intrauterine deaths constitute two thirds and neonatal deaths one third of perinatal mortality among very low birth weight babies. In Turku, neonatal survival rate for infants of 500 to 749 g was 61.5 % and for infants of 750 to 999 g, 77.3 %. In Turku respiratory distress syndrome is one of main complications of prematurity that has led to death in 11.2 % of infants in recent years. Of the survivors, 85 % have been healthy at the age of two years. The incidence of the bronchopulmonary dysplasia among very low birth weight infants has been 19.7 %. In recent years, the incidence of severe brain haemorrhage has been 32 % among infants with a birth weight below 1000 g.     

High urinary concentrations of activin A in asphyxiated full-term newborns with moderate or severe hypoxic ischemic encephalopathy

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) is a major cause of permanent neurological disabilities in full-term newborns. We measured activin A in urine collected immediately after birth in asphyxiated full-term newborns, and assessed the ability of the measurements to predict the occurrence of perinatal encephalopathy. METHODS: We studied 30 infants with perinatal asphyxia and 30 healthy term neonates at the same gestational age. We recorded routine laboratory variables, cranial assessments by standard cerebral ultrasound, and the presence or absence of neurological abnormalities during the first 7 days after birth. Urinary activin A concentrations were measured at first urination and 12, 24, 48, and 72 h after birth. RESULTS: Asphyxiated infants were subdivided as follows: group A (n = 18): no or mild HIE with good prognosis and group B (n = 12): moderate or severe HIE with a greater risk of neurological handicap. Activin A concentrations in urine collected at birth (median collection time at first urination <2 h) and at 12, 24, 48, and 72 h from birth were significantly (P <0.0001) higher in asphyxiated newborns with moderate or severe HIE (Group B) than in those with absent of mild HIE (group A) and controls. Concentrations did not differ between group A and controls. Activin A concentrations were >0.08 mug/L at first urination in 10 of 12 patients with moderate or severe HIE but in none of 18 patients with no or mild HIE. CONCLUSIONS: Activin A measurements in urine soon after birth may be a promising tool to identify which asphyxiated infants are at risk of neurological sequelae.     

Impact of prematurity on perinatal mortality and morbidity.

Severe prematurity is a prime factor causing perinatal mortality or morbidity. In Finland 1% of babies are born before 32 completed weeks of pregnancy and 0.9% are delivered with a birth weight of 1500 g or less. Since transport of a baby in utero is preferable to transporting a neonate, approximately 85% of infants below 1000 g and 90% of infants between 1000 to 1499 g are delivered in departments with facilities for neonatal intensive care. The rate of caesarean delivery is approximately 50% in pregnancies between 26 and 28 weeks, while the overall caesarean section rate is 15%. Deaths of low birth weight babies account for 66% of the total perinatal mortality and those of very low birth weight babies 46%. Intrauterine deaths constitute two thirds and neonatal deaths one third of perinatal mortality among very low birth weight babies. In Turku, neonatal survival rate for infants of 500 to 749 g was 61.5% and for infants of 750 to 999 g, 77.3%. In Turku respiratory distress syndrome is one of main complications of prematurity that has led to death in 11.2% of infants in recent years. Of the survivors, 85% have been healthy at the age of two years. The incidence of the bronchopulmonary dysplasia among very low birth weight infants has been 19.7%. In recent years, the incidence of severe brain haemorrhage has been 32% among infants with a birth weight below 1000 g.     

Outcome of 60 neonates who had ARED flow prenatally compared with a matched control group of appropriate-for-gestational age preterm neonates.

OBJECTIVE: To describe the course and outcome of fetuses with absent or reversed end-diastolic (ARED) flow in the umbilical artery (UA) and to examine the influence of prematurity according to gestational age at delivery. METHODS: Sixty pregnancies complicated by ARED flow in the UA were monitored by repeat Doppler measurements of arterial and venous vessels, non-stress tests (cardiotocogram (CTG)) and maternal investigations, and were delivered between 24 and 34 weeks. Fetal outcome was investigated and compared to a control group of appropriate-for-gestational age (AGA) preterm neonates, matched for gestational age. Mortality, birth weight, Apgar scores, postnatal cord arterial pH and need for ventilation were all recorded, as were cases of respiratory distress syndrome, bronchopulmonary dysplasia, persistent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, abnormal neurological findings and those requiring surgical intervention. Additionally, the group of fetuses with ARED flow was divided into three subgroups of different degrees of prematurity (delivery between 24 + 0 and 28 + 6 weeks, delivery between 29 + 0 and 31 + 6 weeks, and delivery after 32 weeks) and compared according to the above parameters. RESULTS: Pre- or postnatal death occurred in 16 cases. Comparing the 44 (61%) that were born alive with the AGA neonates, significant differences were found in birth weight (P < 0.001), arterial pH value (P < 0.001), bronchopulmonary dysplasia (P = 0.002) and intestinal complications (P < 0.01). Prematurity-related complications were: need for ventilation (P = 0.001), respiratory distress syndrome (P < 0.0001), periventricular leukomalacia (P = 0.002) and pathological neurological testing (P = 0.005). CONCLUSIONS: Neonates displaying ARED flow before birth are growth restricted, acidemic at delivery and are at high risk of developing bronchopulmonary dysplasia and intestinal complications. While perinatal mortality seems to be related to abnormal fetal Doppler velocimetry, age at delivery has a significant impact on short-term morbidity. After 32 weeks, morbidity is low and delivery should be considered. It could be speculated from our data that prolongation of pregnancy with Doppler velocimetry monitoring could help to reduce morbidity, although prolongation remains limited in most cases.     

Maternal homocysteine before conception and throughout pregnancy predicts fetal homocysteine and birth weight

BACKGROUND: Increased homocysteine has been associated with pregnancy complications. METHODS: We investigated prospectively the effect of maternal homocysteine on normal pregnancy outcome. The study included 93 women and their offspring; 39 of the women took folic acid during the second and/or third trimesters of pregnancy. We measured homocysteine at preconception; at weeks 8, 20, and 32 of pregnancy; during labor; and in the fetal cord; we also recorded birth weight. RESULTS: Geometric mean (SE) maternal total homocysteine (tHcy) increased between 32 weeks of pregnancy and labor [7.98 (1.05) micromol/L in unsupplemented women and 6.26 (1.07) micromol/L in supplemented women; P <0.0001 for both]. Fetal tHcy was lower than maternal tHcy [6.39 (1.06) micromol/L in unsupplemented pregnancies (P <0.0001), and 5.18 (1.06) micromol/L in supplemented pregnancies (P <0.05)]. Maternal tHcy was correlated from preconception throughout pregnancy (8 weeks, r = 0.708; 20 weeks, r = 0.637; 32 weeks, r = 0.537; labor, r = 0.502; P <0.0001 for all time points) and with fetal tHcy [preconception, r = 0.255 (P <0.05); 8 weeks, r = 0.321 (P <0.01); 20 weeks, r = 0.469; 32 weeks, r = 0.550; labor, r = 0.624 (P <0.0001)]. Mothers in the highest tHcy tertile at 8 weeks of pregnancy were three times [odds ratio, 3.26 (95% confidence interval, 1.05-10.13); P <0.05] and at labor were four times [3.65 (1.15-11.56); P <0.05] more likely to give birth to a neonate in the lowest birth weight tertile. Neonates of mothers in the highest tHcy tertile at labor weighed, on average, 227.98 g less than those of mothers in the low and medium tertiles (P = 0.014). CONCLUSIONS: Supplemented mothers had lower tHcy at labor than unsupplemented mothers, as did their neonates. Maternal and fetal tHcy was significantly correlated throughout the study. Neonates of mothers in the highest tertile of homocysteine weighed less.     

92例前置胎盘的高危因素及围生儿结局观察

目的探讨前置胎盘发生的高危因素及其对妊娠结局的不良影响。方法回顾性分析9年间分娩的92例单胎前置胎盘病例(前置胎盘组)和186例单胎非前置胎盘对照产妇(对照组)的临床资料。结果前置胎盘发生率为0.93%(92/9 620)。前置胎盘组产妇年龄大于对照组(≥35岁,OR=8.75,P<0.01),胎次(≥3次,OR=5.70,P<0.01)产次(≥2次,OR=6.77,P<0.01)、流产次数(≥3次,OR=7.03,P<0.01)、前次剖宫产史(P<0.01)均多于对照组。前置胎盘组新生儿早产发生率高于对照组(47.83%比7.07%,P<0.01),早产儿1min Ap-gar评分低于对照组[(7.04±2.06)分比(9.09±0.81)分,P<0.01],新生儿出生体质量低于对照组(P<0.01);两组新生儿出生性别的差异无统计学意义。结论高龄(≥35岁)、多产(≥2次)、多胎(≥3次)、多次流产(≥3次)及前次剖宫产史的孕妇前置胎盘发生率高,且易导致早产和新生儿窒息,是产前重点监护的对象。     

Evaluation of Depression and Anxiety Levels in Mothers of Babies' Following Due to Premature Retinopathy

AIM

There are significant increases in the survival rates of premature babies owing to rapid developments in medical technology. As the number of premature babies that can survive in neonatal intensive care increases, so does the frequency of complications due to prematurity. The aim of this study was to investigate the depressive and anxiety symptom levels, and factors affecting these, in mothers of infants who were followed up owing to a diagnosis of premature retinopathy (ROP).

Customized fetal weight limits for antenatal detection of fetal growth restriction.

OBJECTIVE: To define cut-off limits for individually adjustable fetal weight standards for the detection of intrauterine growth restriction. DESIGN: Retrospective study, with the outcome measures small-for-gestational age (SGA) birth weight, operative delivery for fetal distress, umbilical artery pH < 7.15, and admission to the neonatal intensive care unit. SUBJECTS AND METHODS: Two hundred and fifteen women considered to be at increased risk of uteroplacental insufficiency were recruited to a study of serial ultrasound scans. Fetal weights were derived using standard formulae and, retrospectively, weight percentiles were calculated after individual adjustment for maternal height, weight in early pregnancy, ethnic group, parity and fetal sex. INTRODUCTION: One or more antenatal scans indicative of fetal weight below the 10th customized percentile were predictive for a SGA neonate at birth (P < 0.001), operative delivery for fetal distress (P < 0.01) and admission to neonatal intensive care (P < 0.01) but not for a low umbilical artery pH (P = 0.6). Receiver-operator curves showed the optimal customized fetal weight percentile limit for predicting an SGA neonate to be the 18th percentile (sensitivity 83%, specificity 79%, positive predictive value 63% and negative predictive value 92%). For the prediction of operative delivery for fetal distress and admission to neonatal intensive care, the optional customized cut-off value was the 8th percentile. CONCLUSIONS: The assessment of fetal weight using ultrasound and an individually-adjusted standard is predictive of growth restriction and perinatal events associated with hypoxia or diminished reserve. The optimal cut-off value for predicting operative delivery for fetal distress or admission to the neonatal intensive care unit suggests that the 10th customized percentile is a good limit for clinical use.     

Morphine clearance and effects in newborn infants in relation to gestational age

OBJECTIVE: We sought to provide a rational basis for morphine administration in preterm infants in the immediate postnatal period by determining the clearance and evaluating the efficacy and adverse effects of a continuous infusion. STUDY DESIGN: Morphine was infused for 2 to 4 days (140 microg/kg over 1 hour followed by 20 microg/kg/h) to 31 ventilator-treated newborn infants (gestational age, 24 to 41 weeks; birth weight, 765 to 4,015 g). Morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations in serum were determined from arterial blood obtained at 2, 12, 24, 48, and 60 hours after the start of morphine infusion at a median postnatal age of 10 hours. RESULTS: The mean +/- SD steady-state morphine concentration, 167 +/- 77 ng/mL, was achieved between 24 and 48 hours of infusion, and morphine-6-glucuronide and morphine-3-glucuronide concentrations did not reach steady state within 60 hours. Morphine clearance (range, 0.8 to 6.5 mL/min/kg) correlated significantly with gestational age (r = 0.60; P < .01) and birth weight (r = 0.55; P < .01). Pain relief did not correlate with the steady-state morphine concentration. However, significantly higher morphine concentrations were found in infants with decreased gastrointestinal motility (187 +/- 82 ng/mL) compared with those without (128 +/- 51 ng/mL; P < .05). CONCLUSIONS: Morphine should be used with caution in prematurely born infants because of its low clearance, which correlates with gestational age.     

Hepatitis B mother-to-child transmission

Approximately 350 million people are estimated to be chronically infected with hepatitis B virus, leading to an important public health problem. In highly endemic areas where 8 to 15% of people are chronically infected with hepatitis B virus, the risk for the neonate to be perinatally infected by the chronically infected mother, then to become chronically infected themselves, is very high. In those countries, the World Health Organization recommends hepatitis B vaccination systematically at birth, independent of hepatitis B virus maternal status. This vaccination program has begun to induce a rapid decrease in the number of acute hepatitis B virus infections and has also had a secondary effect of a decrease in related sequels. Lamivudine (Zeffix^®, GlaxoSmithKline), when associated with the immunization of the neonate, was recently demonstrated to dramatically reduce the residual risk of perinatal transmission. In intermediate and low endemicity areas, a systematic hepatitis B surface antigen screening is recommended during pregnancy, allowing, in the case of positivity, a selective hepatitis B virus neonate immunization during the first 12 h of life. Hepatitis B virus vaccination of children born to hepatitis B surface antigen-positive mothers confers long-term immunity.