Consensus approach to nasal high-flow therapy in neonates.

OBJECTIVE: Nasal high-flow therapy (nHFT) is commonly used for noninvasive respiratory support in the neonatal intensive care unit. Our objective was to determine which aspects of neonatal nHFT have achieved adequate evidence base to support consensus among experienced clinical investigators, and to document areas lacking consensus to promote future investigations. STUDY DESIGN: Prospective, modified Delphi collation of tabular queries related to specific aspects of neonatal nHFT. Seven international nHFT clinical researchers were queried regarding approaches to initiation, escalation, weaning and discontinuing nHFT. Completed tables were reviewed independently by each investigator, results clarified and discussed and areas of consensus determined. RESULTS: Consensus agreement was reached for many aspects of nHFT including: need for adequate heating and humidification, need to prevent nares occlusion, maximum flow rate of 8 l min-1, assessment of fraction of inspired oxygen (FiO2) and work of breathing for either flow escalation or weaning, equivalence of nHFT to nasal continuous positive airway pressure (nCPAP) for noninvasive support of infants of ⩾28 weeks with resolving respiratory distress and use of nHFT for noninvasive support of stable infants on nCPAP. There was general agreement for initial gas flow rates in the range of 4 to 6 l min-1 and for nHFT as primary therapy for mild respiratory distress. There was no consensus on the approach to discontinuing nHFT. CONCLUSIONS: Among an experienced group of nHFT clinical researchers, there was general consensus in the approach to neonatal nHFT. Additional randomized studies are indicated to provide better evidence related to several aspects of nHFT, as well as to identify other clinical conditions where nHFT may provide safe, effective noninvasive support.

Can a Risk Factor Based Approach Safely Reduce Screening for Retinopathy of Prematurity?

Objective. Current American retinopathy of prematurity (ROP) screening guidelines is imprecise for infants ≥ 30 weeks with birth weights between 1500 and 2000 g. Our objective was to evaluate a risk factor based approach for screening premature infants at low risk for severe ROP. Study Design. We performed a 13-year review from Intermountain Health Care (IHC) data. All neonates born at ≤32 weeks were reviewed to determine ROP screening and/or development of severe ROP. Severe ROP was defined by stage ≥ 3 or need for laser therapy. Regression analysis was used to identify significant risk factors for severe ROP. Results. We identified 4607 neonates ≤ 32 weeks gestation. Following exclusion for death, with no retinal exam or incomplete data, 2791 (61%) were included in the study. Overall, severe ROP occurred in 260 (9.3%), but only 11/1601 ≥ 29 weeks (0.7%). All infants with severe ROP ≥ 29 weeks had at least 2 identified ROP risk factors. Implementation of this risk based screening strategy to the IHC population over the timeline of this study would have eliminated screening in 21% (343/1601) of the screened population. Conclusions. Limiting ROP screening for infants ≥ 29 and ≤ 32 weeks to only those with clinical risk factors could significantly reduce screening exams while identifying all infants with severe ROP.

Comparing automated vs manual leukocyte differential counts for quantifying the 'left shift' in the blood of neonates.

OBJECTIVE: The neutrophil 'left shift' can be measured via the immature to total (I/T) neutrophil ratio or the absolute bands per µl using a manual differential count. It can also be measured from an automated differential count by the immature granulocyte percentage (IG%) or the absolute IG per µl. In neonates, it is unknown if the manual or automated differential count is superior. STUDY DESIGN: We directly compared complete blood counts (CBCs) with manual and automated differential counts from infants <90 days old, and documented whether or not each neonate was infected. We developed reference intervals for I/T ratio, bands per µl, IG% and IG per µl using values from non-infected neonates. RESULTS: The database had 10 714 CBCs. The upper reference interval for I/T ratio was 0.29 in the first 48 h and 0.31 thereafter; bands per µl was 3710 µl(-1) in the first 48 h and 1785 µl(-1) thereafter. IG% was 6.2% then 4.2%; IG per µl was 1460 µl(-1) then 613 µl(-1). Statistical performances of the four methods were equivalent for identifying infection. CONCLUSIONS: We developed reference intervals for four methods of quantifying a neonate's 'left shift'. The information from automated differentials is not inferior to that from manual differentials in identifying infections, but automated differentials have the advantages of a larger sample size, being less expensive, and faster performance times.

Congenital chylothorax treated with oral sildenafil: a case report and review of the literature.

Congenital chylothorax (CC) can result from a congenital malformation or an acquired obstruction or disruption of the thoracic duct. Recently, oral administration of the phosphodiesterase-5 inhibitor, sildenafil, was reported to be effective in resolving non-pulmonary lymphatic malformations in infants and young children. We report a case of CC in a late preterm infant with congenital pulmonary lymphangiectasia where octreotide was not effective, but management with oral sildenafil was successful.

Evolving blood pressure dynamics for extremely preterm infants.

OBJECTIVE: To examine changes in arterial blood pressure (ABP) after birth in extremely preterm infants. STUDY DESIGN: Prospective observational study of infants 23(0/7) to 26(6/7) weeks gestational age (GA). Antihypotensive therapy use and ABP measurements were recorded for the first 24 h. RESULT: A cohort of 367 infants had 18 709 ABP measurements recorded. ABP decreased for the first 3 h, reached a nadir at 4 to 5 h and then increased at an average rate of 0.2 mm Hg h(-1). The rise in ABP from hour 4 to 24 was similar for untreated infants (n=164) and infants given any antihypotensive therapy (n=203), a fluid bolus (n=135) or dopamine (n=92). GA-specific trends were similar. ABP tended to be lower as GA decreased, but varied widely at each GA. CONCLUSION: ABP increased spontaneously over the first 24 postnatal hours for extremely preterm infants. The rate of rise in ABP did not change with antihypotensive therapy.

Evaluating retinopathy of prematurity screening guidelines for 24- to 27-week gestational age infants.

OBJECTIVE: To determine whether current retinopathy of prematurity (ROP) screening guidelines adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants. STUDY DESIGN: Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants of 24 (0)/7 to 27 (6)/7 weeks gestational age (GA) with consent before delivery were enrolled in 2005 to 2009. Severe ROP (type 1 ROP or treatment with laser, cryotherapy or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed the then current AAP (American Academy of Pediatrics) screening recommendations, beginning by 31 to 33 weeks postmenstrual age (PMA). RESULT: One thousand three hundred and sixteen infants were enrolled in the trial. Nine hundred and ninety-seven of the 1121 who survived to first eye exam had final ROP outcome determined. One hundred and thirty-seven (14% of 997) met criteria for severe ROP and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe ROP. PMA at onset was 32.1 to 53.1 weeks. In this referral center cohort, 1.4% (14/997) developed severe ROP after discharge. CONCLUSION: Our contemporary data support the 2013 AAP screening guidelines for ROP for infants of 24 (0)/7 to 27 (6)/7 weeks GA. Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.

Does a highest pre-ductal O(2) saturation <85% predict non-survival for congenital diaphragmatic hernia?

OBJECTIVE: To analyze operative repair, extracorporeal membrane oxygenation (ECMO) and survival rates based on highest pre-ductal oxygen saturation (Pre-O(2)SAT) in a large infant cohort reported to Congenital Diaphragmatic Hernia Study Group Registry between 2000 and 2010. STUDY DESIGN: Analyzed data included gestational age, birth weight, defect side and size, repair, ECMO use, survival and highest reported PaO(2) and Pre-O(2)SAT in first 24 h of life. We excluded 614 infants due to severe anomaly. Pre-O(2)SAT data were available for 1672 infants. RESULT: Among infants with highest Pre-O(2)SAT value <85%, survival (24/105=23%) and repair (55/105=52%) rates were significantly decreased compared with infants with higher values. Survival increased to 44% for infants with highest Pre-O(2)SAT<85% who underwent operative repair. Of these, 83% (20/24) required ECMO support compared with 15% (144/961) of survivors with Pre-O(2)SAT>99% (P<0.001). The lowest reported Pre-O(2)SAT with survival was 32% and for survival without ECMO was 52%. CONCLUSION: A reported highest Pre-O(2)SAT<85% in the first 24 h of life was not uniformly fatal; but survival of infants with Pre-O(2)SAT<85% was associated with high ECMO use and prolonged hospitalization.

High flow nasal cannula versus nasal CPAP for neonatal respiratory disease: a retrospective study.

OBJECTIVE: Our objective is to assess the frequency of usage, safety and clinical utility of humidified high flow nasal cannula (HHFNC) in two tertiary care hospitals and compare outcomes to a historical control group of premature infants who received nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: The first part of the study describes the increased HHFNC usage in two tertiary neonatal intensive care units. The second part compares outcomes of infants, born at less than 30 weeks gestation, who received either NCPAP or HHFNC as an early respiratory support mode. RESULTS: HHFNC usage increased (64%) after its introduction in infants of all gestational ages whereas the usage of NCPAP decreased from 19 to 4%. Ninety-five percent of infants born at less than 30 weeks gestation received HHFNC at some point during their hospital stay whereas only 12% received NCPAP. There were no differences in death or bronchopulmonary dysplasia (BPD), but ventilator-days per patient were decreased (19.4 to 9.9) following introduction of HHFNC. Comparing the cohort of infants who received either NCPAP or HHFNC as an early mode of respiratory support, there were no differences in deaths, ventilator-days, BPD, blood infections or other outcomes. More infants were intubated for failing early NCPAP compared to early HHFNC (40 to 18%). CONCLUSIONS: HHFNC was well-tolerated by premature infants. Compared to infants managed with NCPAP, there were no apparent differences in adverse outcomes following the introduction of HHFNC. Additional research is needed to better define the utility and safety of HHFNC compared to NCPAP.

Single versus repeated-course antenatal corticosteroids: outcomes in singleton and multiple-gestation pregnancies.

The objectives of this study are to compare the neonatal risks and benefits of antenatal single-course versus repeated-course corticosteroids in singleton and multiple-gestation pregnancies. A comprehensive analysis was performed of the inpatient records of all neonates admitted to our center from 1 January 1994 through 31 May 1999. The primary outcome measure was survival without chronic lung disease (CLD). Secondary outcome measures included birth weight; head circumference; interval weight ratios; respiratory disease severity; intraventricular hemorrhage rate and severity; severe retinopathy of prematurity; early infection; and hospital days. All singletons 27-32 completed weeks' gestation, and multiples 26-32 weeks' gestation, whose mothers had received betamethasone before delivery, were included. One hundred and fifteen singleton and 53 multiple-gestation infants (total 168) were stratified by multiplicity, gestational-age (< or =29 or > or =30 weeks), and number of steroid courses. Repeated courses of antenatal betamethasone were not associated with greater survival without CLD, in either singleton- or multiple-gestation infants. In singletons there was no difference in any outcome measure between groups. In multiples, the only difference was greater postnatal weight gain in the lower gestation group. Mean birth head circumference was smaller in repetitively-treated singletons < or =29 weeks. There are no clinically significant neonatal benefits of repeated-course antenatal steroids in singletons > or =27 weeks estimated gestational age (EGA) or multiple-gestation infants > or =26 weeks EGA. Prospective randomized trials of single-course versus repetitive antenatal corticosteroid therapy are warranted.

Deficiencies in lung surfactant proteins A and D are associated with lung infection in very premature neonatal baboons.

Surfactant proteins A (SP-A) and D (SP-D) are important in the innate host defense against pathogenic microorganisms. A deficit in these proteins in premature infants, either because of immaturity or as a consequence of superimposed chronic lung disease (CLD), could increase their susceptibility to infection. The study reported here examined infection in CLD in the premature newborn baboon, and correlated it with the amounts of SP-A and SP-D in lung tissue and lavage fluid. Two groups of baboons were delivered prematurely, at 125 d gestational age (g.a.), and differed principally in whether they developed naturally acquired pulmonary infections and sepsis. Group I animals were ventilated with clinically appropriate oxygen for 6 d and 14 d without clinical incident. Group II animals were ventilated for 5 to 71 d, but differed from those in Group I in that most developed pulmonary infection and/or sepsis. In Group I animals, tissue pools of both SP-A and SP-D were equal to or exceeded those in adults, and lavage pools of SP-A increased progressively with the time of ventilation to about 35% of adult levels after 14 d. In contrast, most Group II animals had concentrations of lavage SP-A that were less than 20% of that in adult animals. A low concentration of lavage SP-A correlated with the release of interleukin-8, and with a high "infection index" based on histopathology, microbiologic cultures, and clinical indications of sepsis. Our data suggest that the amounts of SP-A and SP-D in lavage fluid are indicators of the risk of infection in the evolution of neonatal CLD. Deficits in the amount of lavage SP-A, even after 60 d of ventilation, may have inhibited the resolution of infection and thereby contributed to the developing injury among our Group II animals.

High-frequency oscillatory ventilation: effects on lung function, mechanics, and airway cytokines in the immature baboon model for neonatal chronic lung disease.

Acute lung injury models demonstrate that high-frequency oscillatory ventilation (HFOV) improves lung function, mechanics, and histopathology with reduced inflammatory mediators. Neither human HFOV trials nor premature animal studies have adequately evaluated these factors during prolonged HFOV. The objective of this study was to compare the effect of prolonged HFOV with low tidal volume (VT) positive pressure ventilation (LV-PPV) in an immature baboon model for neonatal chronic lung disease (CLD). After administration of prenatal steroids, 18 baboons were delivered by cesarean section at 125 d (term = 185 d), treated with exogenous surfactant, then randomized to either HFOV or LV-PPV by 5 min age. Animals were maintained on oxygen on an "as needed" basis and on nutritional support for 1 to 2 mo. Serial pulmonary function testing (PFT) was performed. Tracheal aspirates were analyzed for interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-10. Lungs were inflation fixed for morphometric analyses. From 12 h through 10 d age, HFOV animals had consistently lower fraction of inspired oxygen (FI(O(2))) and higher a/ A ratio. Pulmonary mechanics were significantly improved in HFOV animals at nearly every time point analyzed from 12 h to 28 d. There were no consistent differences in tracheal IL-6, TNF-alpha, IL-1beta, or IL-10 after 24 h age. Higher tracheal IL-8 values and macrophage/monocyte numbers were found in LV-PPV animals after 1 wk and 3 to 4 wk ventilation. Both groups exhibited pulmonary pathologic lesions found in extremely immature humans, including alveolar hypoplasia, variable saccular wall fibrosis, and minimal airway disease. HFOV animals had significantly better lung inflation patterns by panel of standards analysis. Early, prolonged HFOV significantly improved early lung function with sustained improvement in pulmonary mechanics out to 28 d. Immature baboons managed with HFOV had less pulmonary inflammation in the hyaline membrane disease (HMD) recovery phase. Though enhanced alveolization was not observed, HFOV for 1 to 2 mo resulted in consistently more uniform lung inflation than LV-PPV.

Neonatal chronic lung disease in extremely immature baboons.

A borderline viability model of bronchopulmonary dysplasia (BPD)/chronic lung disease of infancy (CLD) with pathophysiologic parameters consistent with those in extremely immature humans with BPD/CLD is described. After prenatal steroid treatment of pregnant dams, 12 premature baboons were delivered by cesarean-section at 125 d (term gestation, 185 d), treated with exogenous surfactant, and maintained on appropriate oxygen and positive pressure ventilation for at least 1 to 2 mo. In spite of appropriate oxygenation (median FI(O(2)) at 28 d = 0.32; range, 0.21 to 0.50) and ventilatory strategies to prevent volutrauma, the baboons exhibited pulmonary pathologic lesions known to occur in extremely immature humans of less than 1,000 g: alveolar hypoplasia, variable saccular wall fibrosis, and minimal, if any, airway disease. The CLD baboon lungs showed significantly decreased alveolization and internal surface area measurements when compared with term and term + 2-mo air-breathing controls. A decrease in capillary vasculature was evident by PECAM staining, accompanied by dysmorphic changes. Significant elevations of TNF-alpha, IL-6, IL-8 levels, but not of IL-1beta and IL-10, in tracheal aspirate fluids were present at various times during the period of ventilatory support, supporting a role for mediator-induced autoinflammation. IL-8 levels were elevated in necropsy lavages of animals with significant lung infection. This model demonstrates that impaired alveolization and capillary development occur in immature lungs, even in the absence of marked hyperoxia and high ventilation settings.

Improved outcome of extremely premature infants in the 1990s.

OBJECTIVE: To study the impact of new treatment modalities on premature infants, we compared the effects of surfactant and antenatal steroid use on outcome in two military medical centers. STUDY DESIGN: We performed a retrospective chart review of 234 infants delivered at 22 to 26 weeks estimated gestational age (EGA) at our institutions between 1986 and 1996. The patients were divided into two groups: the presurfactant group included deliveries from 1986 to 1989; and deliveries from 1990 to 1996 were in the surfactant group. RESULTS: At 23 weeks EGA or less, there was only one survivor. At 24 weeks EGA, survival was improved in the surfactant group (46% vs. 5%; p < 0.005). Survival rates at 25 and 26 weeks EGA did not differ significantly. Combined survival at 24 to 26 weeks in the surfactant group exposed to antenatal steroids was 75% versus 44% in the presurfactant group (p = 0.02) Among survivors, the incidence of grade 3 or higher intraventricular hemorrhage was less in the surfactant group (18% vs. 42%; p = 0.038). CONCLUSIONS: Use of surfactant and antenatal steroids are associated with improved survival and decreased incidence of severe intraventricular hemorrhage among the most premature infants delivered in our institutions.

Early prediction of neonatal chronic lung disease: a comparison of three scoring methods.

A variety of postnatal therapies have been and will be evaluated for prevention or treatment of neonatal chronic lung disease (CLD). A simple method for early selection of the highest risk infants would optimize intervention trials. Our study compared a clinical scoring system for predicting neonatal CLD (defined at 36 weeks postconceptional age) with previous regression models developed by Sinkin et al. (Sinkin model) [Pediatrics 1990;86:728-736] and Ryan et al. (Ryan model) [Eur J Pediatr 1996;668-671] in two distinct populations. A respiratory failure score (RFS) was prospectively developed for infants at <32 weeks of gestation admitted to the Wilford Hall Medical Center from January 1990-December 1992. Logistic regression modeling identified three independent predictors of CLD: gestation, birth weight, and RFS. Applying a modified RFS score (to include gestation and birth weight), the RFS, Sinkin, and Ryan models were compared among high-risk infants admitted to Wilford Hall from January 1993-December 1995, and to Crawford Long Hospital (Atlanta, GA) from January 1993-December 1994. Predictive values, sensitivity, specificity, and receiver operating characteristic (ROC) curves were determined for the primary outcome variable: CLD at 36 weeks of corrected gestation. Of 248 infants at <32 weeks admitted to Wilford Hall, 220 survived >7 days. Thirty of 31 (97%) infants diagnosed with CLD were <29 weeks or < or =1,000 g at birth. Despite important demographic and treatment differences between the study populations, similar ROC curves were found for each scoring method when individually evaluated among the three study groups. The RFS method at 72 h demonstrated the greatest area under the ROC curve for prediction of neonatal CLD in the groups as a whole. Application of the RFS method for early prediction of neonatal CLD at age 72 h should improve patient selection for early prevention trials.

Bombesin-like peptide mediates lung injury in a baboon model of bronchopulmonary dysplasia.

The etiology of bronchopulmonary dysplasia (BPD), a chronic lung disease of infants surviving respiratory distress syndrome, remains fundamentally enigmatic. BPD is decreasing in severity but continues to be a major problem in pediatric medicine, being especially prevalent among very premature infants. Increased numbers of pulmonary neuroendocrine cells containing bombesin-like peptide (BLP) have been reported to occur in human infants with BPD. We tested the hypothesis that BLP mediates BPD using the hyperoxic baboon model. Urine BLP levels increased soon after birth only in 100% O2-treated 140-d animals which developed BPD, correlating closely with severity of subsequent chronic lung disease. Similar elevations in urine BLP were observed in the 125-d baboon "interrupted gestation" model of BPD. Postnatal administration of anti-BLP antibody attenuated clinical and pathological evidence of chronic lung disease in the hyperoxic baboon model. Urine BLP could be a biological predictor of infants at risk for BPD, and blocking BLP postnatally could be useful for BPD prevention.

Early high dose antioxidant vitamins do not prevent bronchopulmonary dysplasia in premature baboons exposed to prolonged hyperoxia: a pilot study.

The antioxidant vitamins ascorbic acid (AA) and alpha-tocopherol (alpha-TP) effectively inhibit oxygen free radical-induced lipid peroxidation. Using a premature baboon model of hyperoxia-induced bronchopulmonary dysplasia (BPD), we measured concentrations of AA, alpha-TP, and conjugated dienes (CD, marker of lipid peroxidation) in four animals (hyperoxic antioxidant group) receiving high dose antioxidant vitamin supplementation (AA, 100 mg x kg x(-1) x d(-1); alpha-TP; 20 mg x kg x(-1) x d(-1)) and one animal receiving standard dose antioxidant vitamin supplementation (AA, 10 mg x kg x(-1) x d(-1); alpha-TP, 1 mg x kg x(-1) x d(-1)). Respiratory and histopathologic data were compared with data from 10 historical animals exposed to hyperoxia (hyperoxic control group) and 11 historical animals treated as required with oxygen (normoxic control group) who had received standard dose antioxidant vitamin supplementation. Compared with standard dose antioxidant vitamin supplementation, high dose antioxidant vitamin supplementation effectively raised AA concentrations in plasma (37 +/- 22 micromol/L and 395 +/- 216 micromol/L, respectively) and tracheal aspirates (62 +/- 35 micromol/L and 286 +/- 205 micromol/L, respectively), and alpha-TP concentrations in plasma (10.1 +/- 2.5 micromol/L and 24.6 +/- 17.5 micromol/L, respectively). However, there was no apparent effect on tracheal aspirate CD concentrations (482 +/- 333 micromol/L and 1050 +/- 1111 micromol/L, respectively), and respiratory parameters in the hyperoxic antioxidant group were comparable to those of the hyperoxic control group but significantly worse than in the normoxic control group. Finally, no protective effect of high dose antioxidant vitamin supplementation was noted at the histopathologic level.

Neonatal outcomes of teenage pregnancy in a military population.

OBJECTIVE: To compare the use of prenatal care, incidence of pregnancy complications, and neonatal outcomes among adolescent mothers with those among older mothers in a military population with equal access to a tertiary care center. METHODS: We reviewed the neonatal data base of a military tertiary care center for the period 1990-1996. All singleton births at least 20 weeks' estimated gestational age (EGA) or with birth weight at least 500 g were included. Maternal transfers were excluded. Mothers were divided into five age groups, with the ranges 13-17, 18-19, 20-24, 25-29, and 30 or more years. Prenatal care was assessed by the Kessner index. Data were analyzed by chi 2 test, t test, Mann-Whitney U test, and logistic regression techniques. RESULTS: Included in the study were 10,168 infants (344 aged 13-17, 893 aged 18-19, 3244 aged 20-24, 3095 aged 25-29, and 2592 aged 30 or more years). There was a greater percentage of Hispanic mothers among adolescents aged 13-17 years (48.3%); this percentage decreased as maternal age increased (32.7% to 14.6%). The percentage of white mothers was greatest for mothers over 30 years old (72.1%), and this percentage decreased as maternal age decreased (70.3% to 35.8%). The percentage of black mothers remained relatively constant in all age groups (12.2-16.0%). There were significant differences in sponsor's rank distribution among groups; mothers 25-29 years old and over 30 years old had higher-paying ranks whereas both teenage groups were of predominantly lower-paying ranks. Gestational age at the first prenatal visit and overall use of prenatal care were significantly improved as maternal age increased for each successive age group. Older mothers had significantly higher rates for diabetes and abnormal fetal sonograms than younger mothers; younger mothers had increased rates for sexually transmitted disease, fetal growth restriction, and tobacco use. Multivariate analysis demonstrated that fetal complications, adequate prenatal care, black maternal race, and lower rank were significant independent risk factors for high-risk outcomes. Young maternal age was not an independent risk factor for prematurity or low birth weight. CONCLUSION: Although adolescent mothers (13-17 years old) used prenatal care less than older mothers, there were no differences in the incidence of prematurity, low birth weight (LBW), or neonatal survival among this group of women cared for in a military tertiary health care setting. In this health care setting, risk for premature birth and LBW are related to complications of pregnancy, maternal race, and lower-paying rank.

Oxytocin labor stimulation of twin gestations: effective and efficient.

OBJECTIVE: To test the hypothesis that oxytocin labor stimulation of twin gestations is similar to that of singletons regarding dosage, time, complications, and ability to achieve vaginal delivery. METHODS: This retrospective investigation included 124 gravidas receiving oxytocin for augmentation or induction of labor. Sixty-two women with twin gestations were matched by parity, cervical dilation at initiation of oxytocin, gestational age, oxytocin dosage regimen, and indications for oxytocin to controls with singleton pregnancies. Outcome variables included maximum dosage of oxytocin, incidence of hyperstimulation and fetal heart rate (FHR) abnormalities, time from oxytocin to delivery, cesarean deliveries, and maternal and neonatal outcomes. Statistical analysis was done using McNemar test, paired t test, and Wilcoxon signed-rank test for paired samples. RESULTS: Women with twin pregnancies and those with singletons responded similarly regarding maximum oxytocin dosage (21 +/- 1.5 and 18 +/- 2.4 mU/minute, respectively, P = .1), time from oxytocin to delivery (7.0 +/- 0.8 and 6.7 +/- 0.6 hours, respectively, P = .88), and successful vaginal delivery (90% and 90%, respectively). Oxytocin stimulation of twins resulted in fewer interruptions of the infusion for FHR abnormalities (5% compared with 26%, odds ratio [OR] 0.27, 95% confidence interval [CI] 0.16, 0.47) and hyperstimulation (6% compared with 18%, OR 0.19, 95% CI 0.36, 0.99). CONCLUSION: Twin gestation has no adverse impact on the effectiveness or efficiency of oxytocin labor stimulation. Twin pregnancy seems to be associated with fewer side effects.

Effect of excessive GnRH-binding substance on circulating maternal hCG in human pregnancy.

Gonadotropin-releasing hormone (GnRH) can stimulate the release of placental human chorionic gonadotropin (hCG). Thus, at the onset of these studies it was the objective to define the relationship of hCG to GnRH in the maternal circulation throughout pregnancy, focusing on early pregnancy. Blood samples were collected at 8, 10, 12, 14, 16, 28 and 36 weeks of gestation during labor and the GnRH and hCG levels were determined by radioimmunoassay. Of 39 pregnancies, a GnRH-binding substance was found in the maternal circulation of three. This GnRH-binding substance resulted in erroneous GnRH levels, due to the very high non-specific binding. In the pregnant women without this GnRH-binding substance, GnRH attained highest concentrations at 12-14 weeks. The typical peak of hCG at 8-10 weeks of gestation was observed in this group, while the group of patients having the GnRH-binding substance had significantly lower hCG levels. Each of the patients with circulating GnRH-binding substance had prior pregnancy(s) and two of the three had a prior pregnancy loss. The nature of this GnRH-binding substance was investigated using gel chromatography. After incubation of [125I]GnRH with patient plasma for 3 days this substance was shown to be of high molecular weight which was ethanol precipitable. This binding substance may therefore be an antibody, since it appears to be a high molecular weight protein requiring a number of days to bind the [125I] GnRH. This GnRH-binding substance may be of physiological importance, since the circulating hCG level was significantly less in the group of patients with this substance than in those without.