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Does extracorporeal membrane oxygenation improve survival in neonates with congenital diaphragmatic hernia? The Congenital Diaphragmatic Hernia Study Group.

BACKGROUND/PURPOSE: The benefit of extracorporeal membrane oxygenation (ECMO) in improving survival of neonates with congenital diaphragmatic hernia (CDH) has never been clearly demonstrated. This may be due to comparisons made between treatment groups of unequal illness severity and the low statistical power of analyses from previous studies. The authors analyzed the data from the multicenter CDH registry to determine if ECMO improves survival in CDH neonates with a high risk of mortality. METHODS: A total of 730 neonates were enrolled in the CDH Registry from January 1995 to November 1997. Of these, 632 neonates had a complete data set and were eligible for ECMO by the weight criterion of greater than 2.0 kg. Multivariate logistic regression analysis was used to assess mortality risk for each neonate based on previously validated independent predictors of survival: birth weight and 5-minute Apgar. Five quintile groups were defined based on increasing predictive mortality risk. Multivariate logistic regression and chi2 analyses with birth weight, Apgar score at 5 minutes, and predictive mortality risk as covariates were then performed to assess survival benefit of ECMO compared with conventional therapy alone. Patient survival rate was defined as survival to discharge from hospital. RESULTS: When analyzing all 632 neonates, ECMO neonates (n = 289) had a decidedly lower survival rate (52.9% v 77.3%, P< .001) than non-ECMO neonates (n = 343) without standardizing for the degree of illness. However, when taking into account the patients' predictive mortality risk, ECMO was associated with improved survival in the neonates with mortality risk < or = 80% (P < .05). Furthermore, ECMO was shown to be a positive independent predictor of survival when accounting for the covariates of birth weight, 5-minute Apgar, and mortality risk (P < .05). CONCLUSIONS: ECMO significantly improves survival rates for those CDH neonates with a predictive mortality risk > or = 80%. Generally, the more critically ill the patient with CDH, the more marked the survival benefit obtained.

Extracorporeal Membrane Oxygenation↗

Increased nasal potential difference and amiloride sensitivity in neonates with cystic fibrosis.

Patients with cystic fibrosis (CF) have an increased nasal transepithelial potential difference (PD) which reflects increased sodium absorption across epithelium relatively impermeable to chloride. To evaluate nasal epithelial function in neonates with CF, the PD was recorded and the voltage response to superfusion of 10(-5M) amiloride, an inhibitor of sodium transport, measured between a Ringer perfused bridge on the nasal mucosa and a reference electrode in the subcutaneous space. We studied three neonates with CF with meconium ileus and compared the results with those in 24 term healthy neonates, including one obligate heterozygote for CF, and 27 control neonates with disease. All three CF neonates had raised sweat chloride values (mean 100 mEq/L) at 2 months. The CF neonates had higher PDs (-64.0 +/- 8.4 mV) than those in normal (-24.4 +/- 2.0 mV) or control (-25.8 +/- 2.0 mV) neonates. Superfusion with amiloride induced a 72% reduction in PD in the CF neonates as compared with healthy (37.5 +/- 1.0%) and diseased (36.0 +/- 1.3%) neonates. The PD and amiloride response in CF neonates are similar to those in CF infants (2.24 months), older CF children (greater than 6 years), and CF adults (-64.9 +/- 9.3 mV; 77.7 +/- 1.8%, n = 51). These results suggest that (1) nasal epithelial dysfunction is present in patients with CF shortly after birth, and (2) the nasal PD may be a diagnostic adjunct to the sweat test in the early diagnosis of CF.

Adult↗

In vitro rat bladder function after neonatal estrogenization.

PURPOSE: Experiments were done to evaluate the functional effects of neonatal diethylstilbestrol (DES) treatment on bladder function in male and female Noble rats. MATERIALS AND METHODS: At 5 months after neonatal DES bladders were removed and weighed. Ventral and dorsal bladder strips were prepared to evaluate the effects of neonatal DES on contractile responses to electrical field stimulation, carbachol, adenosine triphosphate, phenylephrine and KCl. Relaxant responses to the catecholamines arterenol (norepinephrine), epinephrine and isoproterenol were also monitored. RESULTS: Neonatal DES resulted in significant increases in bladder mass in males and females. Contractile and relaxant responses were largely unchanged by neonatal DES treatment and the only change observed was a decreased response of ventral strips from male neonatal DES rats to 4 and 8 Hz. stimulation. Ventral strips from male control and neonatal DES rats responded to field stimulation and carbachol with significantly greater responses than dorsal strips and were more sensitive to the relaxant actions of norepinephrine and epinephrine. CONCLUSIONS: The data confirm that neonatal DES causes infravesical obstruction. However, in contrast to published reports of the effects of surgically induced mild outlet obstruction, neonatal DES treatment has little effect on in vitro bladder strip contractile or relaxant function. Thus, the neonatal DES treated rat does not seem to be a useful model in which to study the in vitro effects of partial outlet obstruction on the bladder.

Adenosine Triphosphate↗

Neonatal skin care.

The relative importance of neonatal health and neonatal skin care has been highlighted in recent years as infant mortality rates have decreased while death rates during the neonatal period remain unacceptably high in many areas of the world. During the neonatal period, many newborns develop preventable, clinically apparent skin problems, and many more, especially preterm neonates, experience morbidity caused by compromised skin barrier integrity. Several strategies are available for protecting the integrity and promoting the hygiene of the skin and augmenting its function as a barrier to TEWL and heat loss and the entrance of infectious or toxic agents. Research defining optimal applications of many of these strategies, however, and the development of new approaches in skin care is one of the greatest challenges in pediatric dermatology and holds promise for improving neonatal outcome in the future. The ability to modulate epidermal barrier function and integrity relies largely on the topical use of protective materials and substances and manipulation of the external environment. As understanding of epidermal barrier development advances, perhaps pharmacologic manipulation of barrier development, as now practiced for augmentation of neonatal lung maturity, will become a reality. In the meantime, greater awareness among neonatal health care practitioners of state-of-the-art strategies for optimizing skin integrity in neonates is an important step toward improving neonatal health.

Baths↗

An imbalance between prostacyclin and thromboxane in relation to cerebral blood flow in neonates with maternal preeclampsia.

OBJECTIVE: A disturbance of prostacyclin (PGI2) and thromboxane A2 (TXA2) balance has been reported in preeclampsia. However, little is known about the concentrations of these prostanoids in neonates born to preeclamptic pregnant women. The purpose of this study is to determine whether the PGI2 and TXA2 concentrations are altered and whether the prostanoid balance correlates to the cerebral blood flow in neonates born to preeclampsia. METHODS: Spontaneously voided urine samples were collected from 20 neonates of normotensive and 16 neonates of preeclamptic women during the first 24 h after birth. We measured by radioimmunoassay the concentrations of urinary 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and 11-dehydro-thromboxane B2 (11-dehydro-TXB2), respectively. Blood flow velocity in the middle cerebral artery was studied by pulsed Doppler ultrasonography in the neonates between 17 and 38 h after birth. RESULTS: There was no significant difference between the urinary 6-keto-PGF1alpha in the neonates of mothers with and without preeclampsia (median, 5.3 vs. 3.6 ng/mg of creatinine). In contrast, the urinary 11-dehydro-TXB2 and the ratio of 11-dehydro-TXB2 to 6-keto-PGF1alpha in the neonates of mothers with preeclampsia were significantly lower as compared with the neonates without preeclampsia, respectively (13.7 vs. 20.6 ng/mg of creatinine and 3.0 vs. 5.2, median). The resistance index in the middle cerebral artery was significantly reduced in the neonates with preeclampsia than without preeclampsia (0.67 +/- 0.01 vs. 0.74 +/- 0.02, mean +/- SEM). CONCLUSIONS: There was an association between maternal preeclampsia and the imbalance in the neonatal urinary excretion of PGI2 and TXA2 metabolites. This imbalance may contribute to the regulation of cerebral blood flow.

6-Ketoprostaglandin F1 alpha↗

[Time-course of neonatal precocious mortality between 1994 and 2003 at the Dakar University Teaching Hospital].

OBJECTIVE: To evaluate early neonatal mortality at the University Teaching Hospital and assess changes in the rate and causes during the last ten years. MATERIAL AND METHOD: We performed a retrospective analysis of neonatal deaths recorded at the Neonatal and Premature Unit (NPU) in 2003. The results were compared with earlier evaluations. Comparison of proportions was used for statistical analysis to eliminate the random element in rate variations. The significance threshold was < or =5%. RESULTS: We registered 364 neonatal deaths: 243 among 4853 newborns in our maternity ward and 121 among 213 newborns transferred from a referring maternity. Early neonatal mortality rate 45.5 per 1,000 live births. Mortality particularly concerned newborns with a birth weight < or =2,500 grams (66%) and Apgar scores < or =6. Early neonatal mortality fell significantly since 1994, while overall mortality remained high among newborns transferred from referring maternities. The most frequent causes were premature birth (49%), acute fetal distress (23%) and neonatal infection (18%). CONCLUSION: Early neonatal mortality has decreased remains at a high level. It could be improved by limiting the number of premature births, neonatal suffering and neonatal infection. In a parallel direction we recommend organizing a perinatal network in Dakar.

Apgar Score↗

Determinants of blood pressure in very low birth weight neonates: lack of effect of antenatal steroids.

OBJECTIVES: To define the range of normal blood pressures (BP) for very low birth weight (VLBW;</=1500 g) neonates and to study perinatal variables affecting BP measurements after birth, including the effects of antenatal steroids. STUDY DESIGN: Antenatal steroids were rarely administered at Parkland Memorial Hospital before May 1994, permitting us to establish a cohort of VLBW neonates exposed to antenatal steroids [n=70, 1166+/-253 (S.D.) g, and 28.7+/-2.1 weeks] who were matched with neonates delivered during the prior year (n=46, 1100+/-241 g, 28.9+/-1.8 weeks). Maternal and neonatal charts were abstracted for pertinent data, and neonatal BP measurements (determined directly when an arterial catheter was available or indirectly by the oscillometric method) were extracted every 3 h for the first 12 h and every 6 h until 72 h postnatal. RESULTS: Antenatal steroids did not affect BP immediately after birth or for the subsequent 72 h postnatal. Therefore, data from all neonates </=1500 g were combined and the pattern of BP change over 72 h postnatal assessed. Systolic, diastolic and mean BP increased (P<0.001) 33%, 44% and 38%, respectively, during the first 72 h. Although neonates weighing </=1000 g and 1001-1500 g demonstrated gradual increases (P<0.001) in systolic, diastolic and mean BP by 72 h, values were consistently lower (P<0.01) in neonates </=1000 g. Of interest, only 11 neonates (9.5%) were treated for clinical hypotension. CONCLUSIONS: In VLBW neonates antenatal steroids do not modify BP measurements either immediately after birth or the 30-40% rise occurring in the first 72 h postnatal. Further, BP is developmentally regulated and is gestationally and birth weight dependent. These data provide additional insight into assessing the need for treating hypotension.

Blood Pressure↗

Soluble L-selectin, a marker of immune activation, in neonatal infection.

L-Selectin is an adhesion molecule shed from the surface of lymphocytes and granulocytes upon activation. Soluble L-selectin in the plasma can thus reflect immune activation and is elevated in several pathological states. Our objective was to evaluate plasma levels of L-selectin as an immune activation marker in neonates and to determine whether it can serve as a marker of infection, either neonatal or congenital, or if it is affected by the mode of delivery and obstetrical or perinatal complications. A solid-phase ELISA was used on 89 sera from neonates less than 2 days of age, according to the manufacturer's instructions. Levels of soluble L-selectin in the neonate were lower than those of older infants and children and comparable to the levels seen in adults. There was no difference between levels of soluble L-selectin of premature (median, 1172 ng/ml) and full-term babies (median, 1151 ng/ml) or between babies born via vaginal (median, 1233 ng/ml) or cesarean delivery (median, 1146 ng/ml). Conditions such as preeclampsia or administration of steroids to the mother did not affect the levels of L-selectin in the neonate. In contrast, the presence of maternal clinical chorioamnionitis resulted in an increase in levels of L-selectin in the neonate (median, 1377 vs 1072 ng/ml, p = 0.02), as did neonatal sepsis (median, 1331 vs 1149 ng/ml, p = 0.026). Soluble L-selectin, and thus immune activation level, is highest in neonates with neonatal infection and needs to be further evaluated as a surrogate marker for diagnosing sepsis in the neonate.

Biomarkers↗

[Serum selenium levels in neonates].

BACKGROUND: Despite their increasing importance in children's nutrition, studies on selenium levels in neonates in Spain are scarce and often contradictory. OBJECTIVES: To establish the standard serum levels of selenium in healthy full term neonates in our area and to contribute knowledge of the perinatal factors that influence these levels. METHODS: We determined selenium levels in serum by atomic absorption spectrophotometry in 247 neonates: 70 healthy full term neonates, 60 sick full term neonates, 18 neonates with intrauterine growth retardation (> 37 weeks; birthweight < 2500 g), 44 healthy preterm neonates and 55 sick preterm neonates. RESULTS: Healthy full term newborns showed higher serum selenium levels than healthy preterm neonates (35.11 6.94 g/l, range: 18.4-48 g/l versus 28.65 5.95 g/l, range: 15-44.4 g/l, p < 0.001). In the group with intrauterine growth retardation, serum selenium levels were higher than in the healthy preterm group (30.80 6.97 g/l, range: 20-45.6 g/l versus 28.65 5.95 g /L, range: 15-44.4 g/l) but lower than in the full term and normal birthweight group (idem versus 35.11 6.94 g/l, range 18.4-48 g/l). Likewise, the low birthweight group (< 2500 g) showed lower mean serum selenium levels than the normal birthweight group (27.98 6.75 g/l, range 15-48 g/l versus 33.09 7.52 g/l, range 14.4-48 g/l; p < 0.001). CONCLUSIONS: Prematurity and low birthweight are the best predictors for risk of neonatal hyposeleniemia.

Humans↗

Determinants of weight and length of Indonesian neonates.

OBJECTIVE: To investigate the determinants of neonatal weight and length. DESIGN: From 16-20 week of pregnancy, 366 mothers of the neonates had participated in the community-based study to investigate the effect of weekly supplementation during pregnancy with iron and vitamin A on infant growth. Women from five villages were allocated randomly to receive two tablets each containing 60 mg iron as ferrous sulphate and 250 micro g folic acid (n=121) or two tablets each containing 2400 RE vitamin A in addition to the same amount of ferrous sulphate and folic acid (n=122). A third ('daily') group (n=123) participating in the national iron supplementation programme was recruited from four neighbouring villages. RESULTS: Neonatal weight and length did not differ between the two weekly groups and between the weekly iron group and the 'daily' group. Iron and vitamin A status during pregnancy did not influence neonatal weight and length significantly. Boys were 100 g heavier and 0.53 cm longer than girls (P<0.05). First born neonates were lighter (P<0.01) and tended to be shorter (P=0.070) than neonates of higher birth order. Maternal age and education as well as other socioeconomic determinants were not associated with neonatal weight and length. Neonatal weight was 32% explained by gestational age, maternal weight, postnatal measurement, gender and parity, while neonatal length was 28% explained by gestational age, maternal weight, postnatal measurement, gender and maternal height. CONCLUSIONS: Gestational age, maternal weight at second trimester and infant gender were the main predictors of neonatal weight and length. SPONSORSHIP: The study was supported by The Netherlands Organization for Scientific Research-Netherlands Foundation for the Advancement of Tropical Research (NWO-WOTRO; WV 93-280) and Neys-van Hoogstraten Foundation (IN 114), The Netherlands, and German Agency for Technical Cooperation (GTZ)/South East Asian Ministers of Education Organization (SEAMEO), Indonesia.

Adolescent↗

Neutrophil function in neonates born to gestational diabetic mothers.

OBJECTIVE: To examine neutrophil functional activity in the cord blood of term neonates born to gestational diabetic mothers, in association with the type of diabetes and the development of neonatal hypoglycemia. METHODS: Neutrophil chemotaxis, random motility, and chemiluminescence was evaluated in the cord blood of 30 healthy term neonates: 12 were born to gestational diabetic mothers who received no-insulin (GDM-NI), eight to gestational diabetic mothers who received insulin (GDM), and 10 to mothers without diabetes (neonatal controls). In addition, the neutrophil functional activity in the peripheral venous blood of 10 healthy adults was analyzed. RESULTS: Neutrophil functional activity in the cord blood of the neonates with and without maternal gestational diabetes was significantly lower than that in adults. As compared to neonatal controls, neonates born to both groups of GDM had decreased chemotaxis, random motility, and chemiluminescence (GDM-NI: 52.8+/-2.1 microm, p<0.001, 42.1+/-4.4 microm, p<0.001, and 140.1+/-6.9 counts per minute (cpm) x 10(3), p<0.01, respectively, and GDM: 53.0+/-1.9 microm, p<0.01, 41.8+/-4.0 microm, p<0.001, and 143.0+/-6.8 cpm x 10(3), p<0.01, respectively). Unlike controls, a tight correlation was identified between the tested neutrophil parameters in the cord blood of neonates born to diabetic mothers (r=0.70 to 0.91). The prevalence of hypoglycemia after birth was almost equal (50.0 to 41.7%) in the two groups of neonates born to diabetic mothers. There were differences in the neutrophil functional activity in the cord blood of the neonates with and without hypoglycemia. CONCLUSION: Maternal gestational diabetes leads to impairment of cord blood neutrophil motility and postphagocytic bactericidal capacity independently from the insulin requirements for the maintenance of normoglycemia during pregnancy.

Cell Movement↗

How to identify neonates at risk of death in rural India: clinical criteria for the risk approach.

OBJECTIVE: Majority of neonates in developing countries are born at home and most neonatal deaths occur without receiving medical care. This retrospective analysis was undertaken to develop simple clinical criteria for use in rural community to identify neonates at risk of death. STUDY DESIGN: By analyzing the observational data on two cohorts of neonates in 39 villages in different years of the Gadchiroli field trial, we selected a minimum set of clinical features. We evaluated this set for its sensitivity, specificity and predictive value to detect eventual neonatal death, the primary study outcome. RESULTS: The cohorts included 763 neonates with 40 deaths in 1995 to 1996, a year with minimum interventions, and 1598 neonates with 38 deaths in 1996 to 1998, the years of intensive interventions. On the day of birth, presence of any one of the three: (1) birth weight <2000 g, (2) preterm birth or (3) baby not taking feeds; or, during the rest of neonatal life, mother's report of reduced or stopped sucking by baby, were identified as the predictors of neonatal deaths. The combined set gave a sensitivity of 95%, specificity, 77.3%; predictive value, 18.8%; and the yield, 26.5% in 1995 to 1996 and, respectively, 86.8, 78, 8.8, and 23.5% in 1996 to 1998. The mean lead time gained was 3.4 to 6.6 days. CONCLUSION: Presence of any one of the four predictors will identify with high sensitivity and moderate specificity nearly a quarter of the neonates in rural community as high risk, 3.4 to 6.6 days in advance, for intensive attention at home or referral.

Home Care Services↗

Is home-based diagnosis and treatment of neonatal sepsis feasible and effective? Seven years of intervention in the Gadchiroli field trial (1996 to 2003).

OBJECTIVES: To further evaluate our earlier findings on the feasibility and effectiveness of home-based management of neonatal sepsis by analysing 7 years data (1996 to 2003) from the field trial in Gadchiroli, India. STUDY DESIGN: Neonates in 39 villages were monitored by trained village health workers (VHWs) from 1995 onwards. In 1996, we trained VHWs to diagnose sepsis by using a clinical algorithm and provide domiciliary treatment using intramuscular gentamicin and oral co-trimoxazole. Health records for all neonates were kept by the VHWs, checked by field supervisors, and computerized. Live births and neonatal deaths were recorded by an independent vital statistics collection system. We evaluated the feasibility and effectiveness of this approach. RESULTS: During September 1996 to March 2003, VHWs monitored 93% of all neonates in 39 villages (N=5268). As compared to 552 cases of sepsis diagnosed by computer algorithm, VHWs correctly diagnosed 492 cases (89%). Parents agreed to home-based treatment for the majority of infants (448, 91%), refused treatment in 31 (6.4%) cases, and hospitalized 13 infants (2.6%). VHWs treated 470 neonates with antibiotics, that is, 8.9% of all neonates in community. Of 552 cases diagnosed by computer, VHWs correctly treated 448 (81.2%) and gave unnecessary treatment to 22/470 (4.7%) of treated neonates. The case fatality (CF) was 6.9% in treated cases vs 22% in untreated or 16.6% in the pre-intervention period (p<0.001). Home-based treatment resulted in 67.2% reduction in %CF among preterm and a 72% reduction among LBW neonates. CONCLUSIONS: Home-based management of neonates with suspected sepsis is acceptable to most parents, safe, and effective in reducing sepsis case fatality by nearly 60%. With proper selection, training, and supervision of health workers, this method may be applicable in areas in developing countries where access to hospital care is limited.

Anti-Bacterial Agents↗

Reduced primary antigen-specific T-cell precursor frequencies in neonates is associated with deficient interleukin-2 production.

Clinical evidence has indicated that the neonatal cell-mediated immune response to primary infection is delayed when compared to that of adults with the same primary infection. The mechanisms regulating the development of antigen-specific T-cell immunity in neonates remain to be elucidated. We examined the primary immune response to the non-recall antigen, keyhole limpet haemocyanin (KLH) in adults and neonates in vitro. We report here that conventional bulk culture methods show reduced proliferative responses in neonates although statistical significance was not achieved. Using limiting dilution analysis, the frequencies of KLH-specific T lymphocytes were 10-100-fold lower in neonates when compared to adults. Interleukin-2 (IL-2) production was significantly lower in the supernatants of neonatal mononuclear cells (MNC) stimulated with KLH when compared to adults. Addition of exogenous IL-2 increased precursor frequencies twofold in both adult and newborn cultures. In contrast to the secreted IL-2 levels, IL-2 mRNA expression was higher in antigen-stimulated neonatal MNC preparations, even though proliferation was lower. These observations indicate differential in vitro responsiveness in neonates and adults to primary antigenic challenge. Since no IL-2 was detected in cell lysates, the presence of high levels of IL-2 mRNA and low IL-2 production suggests inability by neonatal MNC to translate IL-2. This deficiency in IL-2 production may explain the reduced precursor frequencies, suggesting failure to recruit T lymphocytes in order to expand the KLH-specific T-cell response. These observations are important for the understanding of the development of primary immune responses and immunological maturation in neonates.

Adult↗

Lymphocyte subpopulations in full-term septic neonates.

PURPOSE: To estimate the absolute leukocyte and lymphocyte counts and relative and absolute sizes of CD19+ B lymphocytes, CD3+, CD4+, CD8+ and CD3+/HLA-DR+ T lymphocytes in full-term septic neonates and the influence of some perinatal risk factors on these lymphocyte subsets. METHODS: Twenty-one septic and mechanically ventilated full-term neonates (13 boys and eight girls) and 15 healthy full-term neonates born vaginally with an Apgar score > 9 and without hyperbilirubinemia were investigated. Two-color flow cytometric immunophenotyping with appropriate antibody panels using lysed whole vein blood was performed. RESULTS: The mean relative and absolute sizes of CD19+ B lymphocytes, CD3+/CD8+ and CD3+/HLA-DR+ T lymphocytes in septic neonates did not differ significantly from control. In contrast, the mean relative sizes of CD3+ and CD3+/CD4+ T lymphocytes and the CD4+/CD8+ ratio in septic neonates were significantly higher than in healthy neonates. With regard to the absolute size in septic neonates, only CD4+ T cells were significantly higher compared with the control group. Perinatal risk factors (birth asphyxia, gestation and delivery complications) had no significant effect on the relative and absolute counts of all estimated lymphocyte subpopulations in septic neonates. CONCLUSIONS: Increases in the relative sizes of CD3+ and CD3+/CD4+ T lymphocytes and the CD4+/CD8+ ratio in full-term septic neonates provides important information about changes in cell-mediated immunity during the early neonatal period.

B-Lymphocyte Subsets↗

Active properties of the urinary bladder: in vitro comparative studies between adult and neonatal rats.

OBJECTIVE: To determine, using in vitro comparative studies, developmental aspects associated with the active properties of the urinary bladder in neonatal and adult rats. MATERIALS AND METHODS: Urinary bladders were removed from neonatal (1-3 days old) and adult (15 weeks old) male Sprague-Dawley rats. Anterior longitudinal muscle strips were obtained from each group and isometric tensions recorded. Nerve-mediated contractions elicited by electrical field stimulation (0.8 ms pulse) or carbachol-induced contractile responses in neonatal and adult bladder strips were compared. Contractile tensions were normalized using the wet weight of the bladder strip or by using the percentage contraction induced by 60 mmol/L KCl. RESULTS: Nerve-mediated contractile responses showed that the muscarinic component predominated in the neonatal rat bladder, which contrasted with the predominant purinergic components in adult bladder. The pattern of spontaneous activity and carbachol-induced contraction differed in the two groups. Small spontaneous contractions in the basal state occurred in adult bladder strips, while short-lived large spontaneous contractions were present in neonatal strips. The amplitude of carbachol-induced contractions generated in the neonatal bladder was larger than that in the adult bladder. In addition, the time to achieve peak contraction elicited by carbachol (5 micromol/L) was shorter in the neonatal bladder. Repetitive carbachol applications induced an attenuation of the contractile response (desensitization), but the neonatal bladder was more resistant to desensitization than the adult bladder. CONCLUSIONS: These results show that nerve-mediated or agonist-induced contractile patterns, and spontaneous activity, in the neonatal bladder differ from those of the adult bladder in rats. The results suggest that in addition to neural immaturity, there are functional differences between the bladders of adult and neonatal rats.

Adenosine Triphosphate↗

Cesarean section on request at 39 weeks: impact on shoulder dystocia, fetal trauma, neonatal encephalopathy, and intrauterine fetal demise.

PURPOSE: The purpose of this analysis was to determine the impact on specific forms of neonatal morbidity and mortality by allowing women to opt for delivery by elective cesarean section at 39 weeks of gestation (EGA). According to the National Vital Statistics Reports, over 70% of deliveries in the U.S. annually are at gestational ages>or=39 weeks EGA. Estimating that over 4 million deliveries occur annually in the United States, this would yield approximately 3 million pregnancies wherein the woman may exercise her choice for either primary or repeat cesarean section at 39 weeks EGA or at the point when labor is established. METHODS: A search was conducted using Ovid Medline spanning the past 10 years using the following key words: fetal trauma, shoulder dystocia, brachial plexus palsy, neonatal skull fracture, obstetrical trauma, traumatic delivery, intrauterine fetal demise, stillbirth, fetal demise, and neonatal encephalopathy. Using this search technique, over 2100 articles were identified. The abstracts were reviewed and pertinent articles were chosen for further consideration. The identified articles and their applicable references were obtained for inclusion in this review. Preference was given to publications on or after the year 2000 with the exception of classical or sentinel articles, which were included without regard to year of publication. RESULTS: Four major categories of neonatal morbidity and mortality are discussed: Shoulder dystocia: Accepting that we do not have a successful method for the prediction or prevention of shoulder dystocia, the question becomes, "What is the chance that a baby will sustain a permanent brachial plexus injury at delivery?" Additionally, is there a significant protective effect of cesarean section in reducing the risk of such injury? Currently, the occurrence rate of brachial plexus palsy at the time of vaginal delivery ranges from 0.047% to 0.6% and for cesarean section from 0.0042% to 0.095%. Using a composite estimate of the risk of 0.15% for vaginal deliveries and applying it to the 3 million deliveries>or=39 weeks EGA, approximately 4500 cases of brachial plexus palsy would occur. If only 15% of these injuries were permanent, 675 permanent brachial plexus palsies would occur annually. If the risk of permanent injury is 1 in 10,000 as reported by Chauhan, 300 permanent brachial plexus palsies would occur annually in the United States. The range then for permanent brachial plexus injury that could be avoided with cesarean section on request would appear to vary between 1 in 5000 and 1 in 10,000 vaginal births. Fetal trauma: The incidence of significant birth trauma varies from 0.2 to 1 to 2 per 1000 births. The use of sequential instruments, for example, vacuum followed by forceps or vice versa, is specifically associated with an unacceptably high injury rate. Intrapartum-related neonatal deaths of vertex singleton fetuses with birthweights>2500 g from traumatic cranial or cervical spine injury secondary to vacuum- or forceps-assisted vaginal delivery are still occurring. Overall, the frequency of significant fetal injury is significantly greater with vaginal delivery, especially operative vaginal delivery, than with cesarean section for the nonlaboring woman at 39 weeks EGA or near term when early labor has been established. Neonatal encephalopathy: The prevalence of moderate to severe neonatal encephalopathy is 3.8/1000 term live births with a neonatal fatality rate of 9.1%. In 4% to 10% of cases, the etiology appears to be pure intrapartum hypoxia. Intrapartum hypoxia superimposed on antepartum risk factors may account for up to 25% of the moderate to severe encephalopathies, according to one cohort. A paradox in the data thus far is that infants born to nonlaboring women delivered by cesarean section had an 83% reduction in the occurrence of moderate or severe encephalopathy. Considering a prevalence of moderate or severe neonatal encephalopathy of 0.38% and applying it to the 3 million deliveries occurring at >or=39 weeks EGA in the United States annually, 11,400 cases of moderate to severe encephalopathy would occur. The rate of encephalopathy observed in infants delivered by cesarean section would yield approximately 1938 cases. This net difference in moderate to severe encephalopathy would represent 9462 cases annually in the United States that could be prevented with elective cesarean section. Although cesarean delivery may be protective for the development of neonatal encephalopathy, to date it has not proven to be protective of long-term neurologic injury in the form of cerebral palsy with or without mental retardation and/or seizure disorders. Intrauterine fetal demise: Copper reported that the rate of stillbirth is consistent from 23 to 40 weeks EGA with about 5% of all stillbirths occurring at each week of gestation. Yudkin reported a rate of 0.6 stillbirths per 1000 live births from 33 to 39 weeks EGA. After 39 weeks EGA, a significant increase in the stillbirth rate was reported (1.9 per 1000 live births). Fretts reported on fetal deaths per 1000 live births from 37 to 41 weeks of gestational age, showing that the rate progressively increased from 1.3 to 4.6 with each week of gestation. It can be estimated that delivery at 39 weeks EGA would prevent 2 fetal deaths per 1000 living fetuses. This would translate into the prevention of as many as 6000 intrauterine fetal demises in the United States annually-an impact that far exceeds any other strategy implemented for stillbirth reduction thus far. CONCLUSION: It is reasonable to inform the pregnant woman of the risk of each of the above categories, in addition to counseling her regarding the potential risks of a cesarean section for the current and any subsequent pregnancies. The clinician's role should be to provide the best evidence-based counseling possible to the pregnant woman and to respect her autonomy and decision-making capabilities when considering route of delivery.

Birth Injuries↗

Neonatal diffusion-weighted MR imaging: relation with histopathology or follow-up MR examination.

PURPOSE: Diffusion-weighted imaging (DWI) has become a standard method for early evaluation of stroke in adults, but its value in neonates is less well established. In this study neonatal DWI was compared with histopathology in those patients who died, or with sequelae seen on a second MR in the surviving neonates. PATIENTS AND METHODS: DWI was performed in 2 groups. Group 1: seven neonates who died and had a post-mortem ex-amination (perinatal asphyxia [n=5], symptomatic hypoglycemia [n= 11, periventricular leukomalacia [n= 1]). Group 2: six surviving neonates with a second MR examination at three months of age (perinatal asphyxia [n= 21, neonatal stroke[n= 3], meningo-encephalitis [n= 1]). RESULTS: In group l neonatal DWI showed more extensive involvement than conventional MRI in 6 out of 7 patients. These changes were less extensive,however, than seen post-mortem by histopathology in 5 out of 7. In group 2 neonatal DWI showed more extensive involvement than conventional MRI in 2 out of 6; 4 out of 6, however, showed less extensive cystic evolution on follow-up MRI at 3 months than expected from neonatal imaging. CONCLUSION: There was a good relation between hyperintense areas on DWI and areas of cytotoxic edema and neuronal damage on histopathology. In the survivors a second MRI showed cystic evolution in all, but the volume of the cysts was smaller than expected on the basis of the neonatal DWI findings.

Asphyxia Neonatorum↗