Band 38, Heft 4

In preterm infants, feeding with human milk (HM) is a very effective intervention for the prevention of infections and necrotizing enterocolitis (NEC), and for potentially improved neurocognitive and cardiovascular outcomes in the long-term. Hospitals and physicians are advised to recommend HM for preterm and other high-risk infants either by direct breastfeeding and/or using the mother's own expressed milk. Donor HM is the preferred feeding when the mother's own milk is not available in sufficient quantity. While in some countries donor HM has been considered an effective tool in the delivery of health care to infants, skepticism regarding its nutritional and immunological quality has limited its distribution in other countries. The purpose of this paper is to summarize the clinical benefits of donor HM in preterm infants, and to discuss common concerns limiting its distribution as standard care. Clinically, the use of donor HM has been shown to prevent NEC, reduce feeding intolerance and improve long-term outcomes in premature infants. Common concerns, such as slow growth and loss of important biological components of donor HM due to storage and pasteurization, should not be a reason for denial of donor milk. Optimization of banking procedures and of HM fortification is available and should be applied. Banked donor milk should be promoted as standard component of health care for premature infants.

Objective: Rates of vertical HIV transmission between mother and child are low, allowing many HIV positive women to have children with near impunity. In this study, data from the Swiss Mother and Child HIV Cohort Study were used to describe maternal characteristics and their association with pregnancy outcomes in HIV positive women. Study design: HIV positive women were followed prospectively during their pregnancies and deliveries by anonymous questionnaires between January 2003 and October 2008. Adverse pregnancy outcomes included preterm delivery, preeclampsia and gestational diabetes mellitus. Results: This study included 266 HIV positive women, of which 67 (25.2%) were first diagnosed with HIV during pregnancy. Thirty percent (n=80) of the women had pregnancy complications after 24 weeks of gestation. Preterm delivery was noted in 72 (27%) patients. Other complications included preeclampsia (n=7; 2.6%) and gestational diabetes (n=7; 2.6%). Older maternal age was the only risk factor associated with adverse pregnancy outcomes (adjusted odds ratio: 1.06, 95% confidence interval 1.01–1.12, P=0.02). Conclusions: HIV positive women, especially with advanced maternal age, have high-risk pregnancies and should be monitored as in an interdisciplinary setting. The preponderance of initial HIV diagnosis during pregnancy confirms the importance of HIV screening in pregnant women.

Objective: Adipokines have been implicated in metabolic regulation and the immune response thus providing a molecular mechanism for the interaction between these two systems. Retinol binding protein 4 (RBP4) is a novel adipokine that plays a role in the pathophysiology of obesity-induced insulin resistance, as well as in the modulation of inflammation. The aim of this study was to determine whether there are changes in maternal plasma concentrations of RBP4 in pregnant women with acute pyelonephritis. Study design: This cross-sectional study included pregnant women in the following groups: 1) normal pregnancy (n=80); 2) pyelonephritis (n=39). Maternal plasma RBP4 concentrations were determined by enzyme-linked immunoassays. Non-parametric statistics were used for analyses. Results: 1) The median maternal plasma RBP4 concentration was lower in patients with acute pyelonephritis than in those with a normal pregnancy (3709.6 ng/mL, interquartile range (IQR) 2917.7–5484.2 vs. 9167.6 ng/mL, IQR 7496.1– 10,384.1, P<0.001; 2) the median maternal plasma RBP4 concentration did not differ significantly between patients with acute pyelonephritis who had a positive blood culture and those with a negative culture (3285.3 ng/mL, IQR 2274.1–4741.1 vs. 3922.6 ng/mL, IQR 3126.8–5547.1, respectively, P=0.2); and 3) lower maternal plasma RBP4 concentrations were independently associated with pyelonephritis after adjustment for confounding factors. Conclusions: In contrast to what has been reported in preeclampsia, acute pyelonephritis during pregnancy is associated with lower maternal plasma RBP4 concentrations than in normal pregnancy. This finding suggests that the acute maternal inflammatory process associated with pyelonephritis is fundamentally different from that of the chronic systemic inflammatory process suggested in preeclampsia, in which RBP4 concentrations were found to be elevated.

Objective: To determine the possible underlying cause of a false-positive first or second trimester biochemical Down syndrome screening test result by means of second trimester amniotic fluid cytokine level analysis. Methods: A total of 74 consecutive patients undergoing amniocentesis for karyotype analysis at 16–20 weeks' gestation were included in this prospective age-matched case-control study. The study group (n=38) had abnormal first or second trimester screening test results and normal karyotype results, while controls (n=36) included those admitted for genetic amniocentesis for other reasons who had normal first or second trimester screening test and normal karyotype results. Four markers [interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and ischemia-modified albumin (IMA)] were studied in amniotic fluid. Results: The mean age of the women in the study and control groups was 34.0±5.6 and 33.6±7.2 years, respectively. The women in the study and control groups had similar clinical and laboratory characteristics. The mean amniotic fluid IL-6 (414.84±83.96 vs. 343.02±110.59, p=0.002) and IL-8 (377.61±243.31 vs. 261.90±201.29, p=0.029), TNF-α (24.91±5.78 vs. 21.60±5.55, p=0.014), and IMA (1.19± 0.10 vs. 1.05±0.12, p<0.001) values were significantly increased in the study group when compared to controls. Conclusion: The higher amniotic fluid cytokine and ischemia-modified albumin levels in patients with false-positive first or second trimester biochemical Down syndrome screening test may result from subclinical fetal membrane inflammation and/or ischemia.

Aims: We investigated the genital group B streptococcus (GBS) carrier rate in Korean pregnant women and the serotype distribution in face of the recent increase of late-onset GBS disease in Korea. Methods: GBS screening was performed on 4045 healthy pregnant women at 35–37 weeks' gestation. In case of positive GBS culture, serotyping was performed by using GBS typing antisera. Results: When both vaginal and anorectal culture were performed, the GBS carrier rate was 10.0% (n=121/1205), which is the highest rate ever reported in Korea. Type III was more common (36%), and type Ia (13%) and Ib (7%) were less prevalent. Conclusions: Increased maternal genital GBS carrier rate and difference in serotype distribution pattern of GBS may be related to the recent increase of late-onset GBS disease in Korea.

Objective: This retrospective study was performed to characterize the laboratory features and water metabolism of women with pregnancy-induced antithrombin deficiency (PIATD). Methods: Among 1493 women who gave birth to a singleton infant at our institution, 114 women who developed PIATD and/or pregnancy-induced hypertension (PIH) were reviewed with respect to perinatal changes in laboratory variables (hematocrit value, fibrinogen, fibrinogen degradation product, D-dimer, uric acid, aspartate aminotransferase, lactate dehydrogenase) and body weight. PIATD was defined as a gradual decline in antithrombin (AT) activity to ≤65% of normal activity levels. One hundred and fourteen women with neither PIATD nor PIH and matched for the cesarean delivery rate were selected as a control group. Results: Of the 81 women who developed PIH, 19 (23.4%) also developed PIATD. Thirty-three women developed PIATD in the absence of PIH. Coagulation-fibrinolysis was significantly more enhanced and the postpartum reduction in the hematocrit value was significantly larger in women with PIATD, irrespective of the presence or absence of hypertension, than in women without PIATD. The postpartum decrease in body weight was significantly smaller in women with PIATD, irrespective of the presence or absence of hypertension. Conclusions: A decrease in AT activity may occur in the absence of hypertension. Even in the absence of hypertension, a decreased plasma volume and enhanced coagulation-fibrinolysis seem to characterize women with PIATD. The monitoring of AT activity may help in distinguishing pregnant women with these insidious risks.

Objective: Acute hypoxia is one of the main causes of poor neonatal outcome. The aim of this study was the investigation of cardiac output (CO) and blood flow redistribution following induction of acute hypoxia in a fetal sheep model. Method: We investigated 10 fetal sheep between 108 and 130 days of gestation. Acute hypoxia was induced by reducing the O 2 saturation in the ventilated gas mixture of the maternal sheep to ∼75%. The CO, placental fraction of CO, Doppler parameters in the ductus venosus (DV), umbilical artery (UA) and vein (UV) were measured. Results: The fetal pO 2 decreased from 47.1 (7.19; 7.35) to 6.89 (6.78; 7.11) mm Hg [P=0.01, median, (95% CI)] during hypoxia. Fetal pH and BE were also significantly reduced. The DV/UV fraction increased from 15.3 (11.5; 19.8) to 51.1 (35.9; 62.1) (P=0.0001). The combined cardiac output [1228.1 (1024.3; 1686.4) vs. 987.8 (834, 1261) mL min –1 ], the placental fraction of the CO [31.5 (26; 42.1) vs. 26.9 (20.6; 29.3)%] and the right to left (R/L) heart ratio [1.76 (1.5; 2.2) vs. 1.3 (1.1; 1.6)] significantly decreased during hypoxia. Conclusions: Acute hypoxia significantly increases the proportion of the placental blood passing through the DV and reduces the placental fraction of CO and the R/L heart ratio. These findings could be used as early signs of acute fetal hypoxia.

Aim: Prenatal and neonatal overfeeding programs a permanent obesity and diabetes disposition, e.g., due to induction of hypothalamic insulin resistance. We investigated acquired alterations of the DNA methylation pattern of the hypothalamic insulin receptor promoter (IRP) which might be an underlying molecular mechanism. Methods: Neonatal overfeeding was induced by rearing Wistar rats in small litters (SL). Methylation of CpG-dinucleotides of the hypothalamic IRP was mapped using bisulfite sequencing. Results: Neonatal overfeeding led to rapid early weight gain, resulting in a metabolic syndrome phenotype, i.e., obesity, hyperleptinemia, hyperglycemia, hyperinsulinemia, and increased insulin/glucose-ratio. The proportion of animals carrying any methylated CpG residue in the 322 bp CpG island of the IRP was increased in neonatally overfed SL rats (n=8), as compared to controls (n=8; P=0.04). Moreover, the mean percentage of methylated CpG positions was also higher in SL rats (P=0.01). Over both groups, neonatal blood glucose levels were positively correlated to the extent of promoter methylation (r=0.52; P=0.04). Conclusions: This study characterizes for the first time the IRP epigenomically in any species and tissue. Our data reveal that the IRP is vulnerable to hypermethylation due to overnutrition, probably especially glucose-dependent in a dose-response manner. This paradigmatically indicates the impact of nutrient-dependent epigenetic malprogramming, leading to a “diabesity” disposition which may become pathogenic throughout life.

Aims: To ascertain risk of aneuploidy, infection and neurological abnormality for the fetus diagnosed with isolated mild (10.1–12.0 mm) to moderate (12.1–15.0 mm) cerebral ventriculomegaly and to compare the neurological outcome between symmetrical vs. asymmetrical and stable vs. progressive ventriculomegaly. Methods: A systematic review was conducted. Literature was identified by searching two bibliographical databases between 1980 and 2009 without language restrictions. The data extracted were inspected for heterogeneity. Overall rates and confidence intervals (CIs) for each prognostic factor were calculated. When comparative data existed, the odds ratio (OR) was calculated. Results: The search strategy yielded 2150 relevant citations of which 28 studies were included in the review. The overall rate of infection and chromosomal abnormality was 1.5 and 5% (95% CI 3, 7), respectively. The risk of neurological abnormality regardless of karyotype or infection screen was 14% (95% CI 10, 18) and this reduced to 12% (95% CI 9, 15) when both chromosomes and infection screen were normal. The risk of neurological abnormality was significantly lower in stable compared to progressive ventriculomegaly [OR 0.29 (95% CI 0.15, 0.58)]. No significant differences were detected when symmetrical vs. asymmetrical ventriculomegaly were compared [OR 0.91 (95% CI 0.34, 2.41)]. Conclusion: This systematic review provides the physician with some estimates of prognosis in cases of isolated mild to moderate ventriculomegaly.

Background: A model to predict hospitalization due to respiratory syncytial virus (RSV) of infants born at 33– 35 weeks' gestation was developed using seven risk factors from the Spanish FLIP study “birth ±10 weeks from the beginning of the RSV season”, “birth weight”, “breast fed ≤2 months”, “number of siblings ≥2 years”, “number of family members with atopy”, “number of family members with wheezing”, and “gender”. The aim of this study was to validate the model using French data. Methods: The FLIP model [predictive accuracy 71%, receiver operating characteristic (ROC) 0.791] was tested against the French data (77 hospitalized infants with RSV born at 33–35 weeks and 154 age-matched controls) using discriminatory function analysis by applying the FLIP coefficients to the French data and by generating the seven variable model from the French data. Results: Applying the FLIP coefficients to the French dataset, the model correctly classified 69% of cases (ROC 0.627). The predictive power increased to 73% (ROC 0.654) when “number of siblings ≥2 years” was substituted for “number of children at school”. The number needed to treat (NNT) in order to prevent 70% of hospitalizations was 18. The model derived using French data could correctly classify 62% of cases in the French data (ROC 0.658). Conclusions: The model was successfully validated and may potentially optimize immunoprophylaxis in French infants born at 33–35 week's gestation.

Objective: To compare outcomes of extremely low birth weight (ELBW) infants exposed to no antenatal steroids (ANS); incomplete ANS and complete course of ANS at varying intervals prior to delivery. Methods: A retrospective review was performed on 169 ELBW infants with ANS exposure at varied dose-intervals. The odds of mortality, intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD) were compared between Group 1, infants born without ANS exposure, Group 2, infants born after one dose of ANS, Group 3, infants born after two doses of ANS given within a week, and Group 4, infants born after two doses of ANS >7 days prior to delivery. Results: Mortality and IVH were significantly lower in Groups 3 (30% and 10%) and 4 (15% and 30%), compared to Groups 1 (56% and 69%) and 2 (56% and 38%). Increasing gestational age and exposure to complete course of ANS were significantly associated with decrease in mortality, BPD/mortality and IVH. Infants who received one dose of ANS had significantly lower incidence of severe IVH compared to infants without ANS exposure. Conclusions: Beneficial impact of ANS on mortality and composite BPD/mortality is evident only after a complete course and persists even with its administration beyond a week from delivery.

Neonatal anthropometric data reflect intrauterine development and correlate with postnatal outcome. Therefore, classification of neonates by body dimensions, using gestational age-adjusted population percentiles, is clinically practiced. However, neonatal anthropometric variables are also influenced by maternal constitution and the extent of this influence is currently unknown. We analyzed small for gestational age (SGA) and large for gestational age (LGA) rates according to maternal height and weight. We used data of about 2.3 million singleton pregnancies from the German Perinatal Survey of 1995–2000. A close correlation between maternal and neonatal anthropometric data was found; SGA rates were inversely proportional and LGA rates were directly proportional to maternal height, weight, and body mass index. Neonates of small and light mothers (<155 cm, <50 kg) had, according to the presently used classification scheme, an SGA rate of 25.3% and an LGA rate of 1.7%, respectively. Newborns to tall and heavy women (>179 cm, >89 kg) had a much lower SGA rate (3.1%) and a much higher LGA rate (30.6%). Neonatal body length and head circumference depended on maternal stature in a similar way. Some neonates who are “appropriate” for their gestational age in that they achieve their genetically determined growth potential are therefore apparently misclassified as SGA or LGA.

A retrospective cohort study on nosocomial infections (NI) in the neonatal intensive care unit (NICU) was performed in the Children's Hospital of Zhejiang University, Hangzhou district, China. The most common infection site was pneumonia and bloodstream infection. Low admission age, long NICU stay, and mechanical ventilation were significant risk factors for NI. Klebsiella pneumoniae was the most common pathogen, followed by Acinetobacter baumannii , Staphylococcus epidermidi , Pseudomonas aeruginosa , Enterobacter cloacae , and Stenotrophomonas maltophilia . Antibiotic resistance of the isolated bacterium was high. In conclusion, this study described the clinical characteristics of NI in a Chinese NICU, which might contribute to implementation of more effective therapeutic and preventive strategies.

Aims: Fetoscopic laser photocoagulation (FLP) has become standard therapy for severe twin-twin transfusion syndrome. Data on adverse maternal events are rare. We performed a literature review to obtain data on maternal complications of FLP. Methods: Extensive literature review, searching MEDLINE and other databases from 1990 to 2009, using MESH-terms and further keywords. Data extraction was performed using the following criteria: (i) maternal complications reported as primary or secondary outcome parameters; (ii) any comment on adverse maternal events. Results: Of 321 publications found 40 were included, comprising 1785 patients. The overall rate of adverse maternal events was 5.4%. In studies with systematic assessment (n=3, 379 patients) the complication rate was significantly higher (17.4% vs. 2.2%, P<0.0001). Adverse events were classified and the rate was 1.0% (1.8% vs. 0.8%, P=0.12) for severe complications; 2.9% (11.9% vs. 0.5%, P<0.0001) for intermediate/minor adverse events; and 1.5% (3.7% vs. 0.9%, P<0.0001) for complications with undetermined relevance. Conclusions: High-quality data on maternal complications of FLP are rare. With systematic assessment, the rate of adverse events is significantly higher. Underreporting has to be assumed. Further studies are required to confirm these data.

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