Fetal heart rate characteristics at 25 to 28 weeks' gestation

The objective of this article is to define normative fetal heart rate (FHR) tracing characteristics between 25-28 weeks' gestation in a low-risk population with normal pregnancy outcomes and to determine which criteria best determine FHR reactivity. Continuous FHR tracings were reviewed from 188 low-risk women participating in a trial of the Mammary Stimulation Test (MST) at 25-28 weeks' gestation. A reactive tracing required the presence of > or =two accelerations in 20 min. Different acceleration criteria were evaluated based upon the width of the acceleration (short vs. long) and the amplitude of the acceleration (10 vs. 15 bpm). Seventy-one percent of the FHR tracings were reactive using the higher amplitude (15 bpm), short criteria. This number increased significantly to 92% when the lower amplitude (10 bpm), short criteria were used (p <0.01). As gestational age advanced, there was a trend toward increased reactivity irrespective of which criteria were used, but these differences were not significant. Reducing the acceleration amplitude criteria to 10 bpm in preterm pregnancies will maximize the number of reactive nonstress tests. This is advantageous because it would improve test specificity and decrease the false-positive rate. Our findings need to be prospectively validated in a high-risk population.     

Transepidermal water loss in infants born at 24 and 25 weeks of gestation

Bone tissue undergoes continual renewal in order to keep the mechanical competence of the bone matrix. This is performed by two cells: osteoclasts which resorb the calcified matrix and osteoblast which synthetize a new bone matrix. Biochemical markers of bone remodelling allow the evaluation of the activity of each type of bone cells. An unbalance in this process induces modifications of the amount of calcified tissue and of the bone microarchitecture. Several technics based on X-ray and ultrasound allow a non invasive evaluation of these modifications.     

Thyroxine values from newborn screening of 919 infants born before 29 weeks' gestation

OBJECTIVES: Severe transient hypothyroxinemia in premature infants is associated with cerebral palsy and mental retardation: this study assessed its prevalence in very premature infants. METHODS: Congenital hypothyroidism screening programs in three states provided thyroxine values for 919 newborn infants younger than 29 weeks who were enrolled in a multicenter study. RESULTS: Thyroxine values were lower than 4.0 micrograms/dL in 21% of survivors and increased each week by 0.6 microgram/dL (95% confidence interval [CI] = 0.4, 0.7). At tests done 1 to 2 days after birth, levels were 2.5 micrograms/dL higher (95% CI = 1.8, 3.3) than at tests done at 8 to 14 days. In New York, levels were 1.0 microgram/dL higher (95% CI = 0.3, 1.6) than elsewhere. The levels of infants who died were 1.3 micrograms/dL lower (95% CI = 0.6, 2.0) than those of survivors. CONCLUSIONS: Severe transient hypothyroxinemia is common in very premature infants and deserves further study.     

Chronic oxygen dependency in infants born at 24-32 weeks' gestation: the role of antenatal and neonatal factors

OBJECTIVES: To study the incidence of chronic oxygen dependency (COD) among ventilated survivors born at 24-32 weeks gestation from 1986 to 1994 and to identify antenatal and neonatal factors that may have changed with time; and to identify antenatal and neonatal factors that could contribute to the development of COD in infants born at 24-32 weeks gestation using a case control model. METHODOLOGY: Infants born at 24-32 weeks gestation in one tertiary referral centre between 1986 and 1994 and admitted to the neonatal intensive care unit for respiratory support were studied. Data accumulated prospectively since 1986 in survivors of ventilation were analyzed to identify antenatal and neonatal factors that could have changed with time. The cohort of infants who developed COD were matched for gestation and time of birth with a control group of infants who did not have COD. Significant factors that could have contributed to the development of COD were identified using forward logistic regression analysis. RESULTS: The number of mothers admitted for threatened premature labour (TPL), and pregnancy induced hypertension decreased with time while the use of antenatal steroids and maternal antibiotics increased. More infants were delivered by Caesarean section during the later years. There was an increase in neonatal septicaemia with time while there were decreases in hyaline membrane disease, pneumothorax, pulmonary interstitial emphysema, use of high peak inspiratory pressure (PIP) and high inspired oxygen. The incidence of COD decreased. The case controlled study revealed a significant positive association between COD and male gender, birthweight less than the 10th percentile for gestation, PIP over 30 cm H2O, septicaemia and significant patent ductus arteriosus (PDA) requiring indomethacin. There was a negative association with TPL. CONCLUSIONS: Further decrease in COD can be achieved only if septicaemia, PDA and the use of high PIP can be avoided. The most effective way of reducing the incidence of COD is by reducing the incidence of prematurity.     

Speech and language development of children born at < or = 32 weeks' gestation: a 5-year prospective follow-up study

Speech and language comprehension and production were assessed at the age of 5 years in a cohort of children born preterm at < or = 32 weeks' gestational age (N=55) in comparison with children born at term and of similar age, sex, and social backgrounds. Data both including and excluding major neurological disabilities are presented. Mean performance for the entire group of preterm children was significantly lower than for the controls on most of the measures including the composite IQ scores. When the nine children who had major neurological disabilities were excluded from the preterm group, statistically significant differences were found on four of the total 12 speech and language measures. Intellectually normal preterm children without major neurological disability were slower than the controls on rapid word retrieval. In addition, difficulties in comprehending relative concepts were typical for the preterm children. The results suggest 'subtle dysnomia', which is indicative of later reading problems. On global verbal measures and on the basic speech and language aspects the study groups did not differ. Specific language impairment, defined as a discrepancy of > 1SD between Performance IQ and Verbal IQ scores, showed a tendency to be more common in the control group. Within both the study groups, the boys showed a tendency for a greater discrepancy between their Performance and Verbal IQ scores.     

Transvaginal sonographic diagnosis of short-rib polydactyly dysplasia at 13 weeks' gestation

Short-rib polydactyly dysplasia (SRP) is an autosomal recessive, lethal skeletal dysplasia. Sonographic assessment of subsequent pregnancies is, therefore, recommended. This case indicates that this diagnosis can be made in the latter part of the first trimester. A 30-year-old multigravid woman presented at 13 weeks' gestation for an ultrasound examination. She had had a termination of pregnancy for a fetus with pathologically confirmed short-rib polydactyly dysplasia, type I (Saldino-Noonan). On transvaginal sonography, a narrow chest, symmetrical micromelia, polydactyly and anasarca were present. An autopsy confirmed recurrent SRP. Short-rib polydactyly dysplasia may be diagnosed with transvaginal sonography in the first trimester.     

A two-dimensional protein map of human amniotic fluid at 17 weeks' gestation

Using updated technical procedures (immobilized pH gradients for isoelectric focusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis: IPG/SDS-PAGE) we provide a two-dimensional (2-D) map of amniotic fluid (AF) proteins. This map comprises over 800 silver-stained spots. Over 150 spots have been identified by matching on the net with human plasma and cerebrospinal fluid maps available from SWISS 2DPAGE database; several additional spots were assigned by immunoblotting and/or microanalytical techniques. This report details our investigation on AF proteins focusing on the 17th week of gestation, when AF is most commonly used for clinical evaluation of fetal disorders. As a whole, the map displays a number of potential markers for fetal development and for gestation abnormalities. The 2-D electrophoretic technique allows the monitoring of all these proteins at the same time along with additional spots that may prove of diagnostic significance.     

Developmental outcome of infants born with biological and psychosocial risks

The significance of prenatal and perinatal complications (biological risk) and of family adversity (psychosocial risk) on early child development was examined in a prospective study. Developmental outcome of 350 infants was assessed by measures of motor, cognitive, and social-emotional functioning at 3, 24, and 54 months. Results indicated a differential impact of risk factors on specific outcomes. Whereas psychosocial risks became more prominent with growing age and were related to poorer child outcome in all areas of functioning, biological risks decreased in influence and predominantly resulted in poorer motor development. The contributions of biological and psychosocial risks on outcomes were additive. A number of individual risk factors emerged as significant predictors of later maladaptation.     

Increased survival and deteriorating developmental outcome in 23 to 25 week old gestation infants, 1990-4 compared with 1984-9

AIMS: To assess whether changes in survival over time in infants of 23 to 25 weeks of gestational age were accompanied by changes in the incidence of disability in childhood during an 11 year period. METHODS: Obstetric and neonatal variables having the strongest association with both survival to discharge from a regional neonatal medical unit and neurodevelopmental disability in 192 infants of 23 to 25 weeks of gestation, born in 1984 to 1994, were studied as a group and in two cohorts (1984 to 1989 n = 96 and 1990 to 1994 n = 96). The data collected included CRIB (clinical risk index for babies) scores and cranial ultrasound scan findings. The children were followed up at outpatient clinics. RESULTS: Between 1984 and 1989 (cohort 1) and 1990 and 1994 (cohort 2) the rate of survival to discharge increased significantly from 27% to 42% and the rate of disability in survivors increased from 38% to 68%; most of this increase was in mild disability. The proportions of survivors with cerebral palsy did not alter significantly (21% vs 18%), but more survivors with blindness due to retinopathy of prematurity (4% vs 18%), myopia (4% vs 15%) and squints (8% vs 13%) contributed to the increased rate of disability. Clinically significant cranial ultrasound findings and a high CRIB score were strongly associated with death. A high CRIB score was most strongly associated with disability. CONCLUSIONS: The rise in disability with improved survival was not due to cerebral palsy; rather the main contributors were blindness due to retinopathy, myopia, and squint. The causes of these disabilities seem to be linked to high CRIB scores. A system of regular and skilled retinal examination and access to facilities for retinal ablation should be in place in all neonatal units which undertake the care of such extremely preterm infants.     

Identifying twin gestations at low risk for preterm birth with a transvaginal ultrasonographic cervical measurement at 24 to 26 weeks' gestation

OBJECTIVE: Because twins are a high-risk group for preterm birth, many clinicians routinely use prophylactic interventions such as home bed rest, hospital bed rest, oral tocolytics, or home uterine activity monitoring to prevent preterm delivery. We sought to identify twin gestations at low risk for spontaneous preterm birth with transvaginal ultrasonography of the cervix to avoid the unnecessary use of prophylactic interventions in these pregnancies. STUDY DESIGN: We measured cervical length at 24 to 26 weeks' gestation by transvaginal ultrasonography in women with twin gestations referred to our prematurity prevention clinic. Each delivery was classified as (1) spontaneous preterm birth < 34 weeks' gestation, (2) delivery at > or = 34 weeks' gestation with intervention, or (3) delivery at > or = 34 weeks' gestation without intervention. Intervention included strict bed rest at home or in the hospital, either parenteral or oral tocolysis, or both, or home uterine activity monitoring. Indicated preterm deliveries and patients with cerclage were excluded from this analysis. The ability of transvaginal cervical length to predict women who would deliver at > or = 34 weeks without intervention was evaluated. A cervical length of 35 mm was chosen by scatter diagram as the best cutoff to discriminate between the group delivered at term without intervention and the other two groups. RESULTS: Of 85 women with twin gestations who underwent ultrasonographic cervical length measurements at 24 to 26 weeks' gestation, 17 had spontaneous preterm birth at < 34 weeks, 23 were delivered at > or = 34 weeks but required intervention, and 45 were delivered at > or = 34 weeks without intervention. The mean cervical length for those delivered at > or = 34 weeks' gestation without intervention (36.4 +/- 5.8 mm) was significantly greater (p < 0.0001) than the mean for those delivered preterm (27.4 +/- 8.5) and those delivered at > or = 34 weeks' gestation who required intervention (27.7 +/- 10.5 mm). The sensitivity, specificity, and positive and negative predictive values of a cervical length > 35 mm for predicting delivery at > or = 34 weeks' gestation are 49%, 94%, 97%, and 31%, respectively. CONCLUSION: A transvaginal ultrasonographic measurement of the cervix of > 35 mm at 24 to 26 weeks in twin gestations can identify patients who are at low risk for delivery before 34 weeks' gestation.     

The effect of combined antenatal vitamin K and phenobarbital therapy on umbilical blood coagulation studies in infants less than 34 weeks' gestation

OBJECTIVE: To determine if antenatal vitamin K and phenobarbital therapy affect coagulation studies in umbilical blood at birth, and to provide 95% reference ranges for umbilical blood coagulation parameters in premature gestations. METHODS: Patients at imminent risk for spontaneous or indicated premature delivery less than 34 weeks' gestation were randomized to receive either placebo or vitamin K and phenobarbital. Prothrombin time (PT), activated partial thromboplastin time (PTT), functional coagulation factors, and decarboxylated prothrombin assays were performed on umbilical blood specimens. Decarboxylated prothrombin, also known as "protein induced by vitamin K absence-factor II" or precursor prothrombin, is a sensitive marker for vitamin K deficiency. Standardized values of PT and PTT are reported in seconds and standardized values of factor assays in percentage of normal adult functional activity (mean +/- one standard deviation). RESULTS: Newborns in the placebo and treatment groups had similar umbilical blood PT (12.6 +/- 1.2 versus 12.7 +/- 1.4 seconds), PTT (48.8 +/- 13.4 versus 49.6 +/- 13.8 seconds), and functional activity of factor II (40.3 +/- 12.5 versus 42.0 +/- 12.1%), factor VII (67.0 +/- 20.9 versus 66.8 +/- 18.9%), factor IX (27.4 +/- 12.8 versus 25.8 +/- 8.9%), and factor X (47.0 +/- 12.8 versus 49.2 +/- 11.6%). Newborns in the treatment group were about half as likely as those in the placebo group to have detectable decarboxylated prothrombin levels in umbilical blood at birth (gestational age-adjusted odds ratio 0.47, 95% confidence interval 0.22-1.01; P = .05). CONCLUSIONS: Combined maternal therapy with vitamin K and phenobarbital before premature delivery does not affect umbilical blood PT, PTT, or functional activity of vitamin K-dependent coagulation factors II, VII, IX, and X. However, it is associated with the reduced presence of decarboxylated prothrombin in umbilical blood at birth. There is significant improvement in umbilical blood coagulation tests as gestational age advances from 24 to 34 weeks.     

Functional abilities at age 4 years of children born before 29 weeks of gestation

OBJECTIVES: To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN: Cohort study of a geographically defined population of babies. SETTING: Oxford Regional Health Authority. SUBJECTS: All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES: Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS: Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS: With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.     

Management of pregnancies beyond forty-one weeks' gestation with an unfavorable cervix

OBJECTIVE: Our purpose was to determine the optimal management of pregnancies beyond 41 weeks' gestation with a cervix unfavorable for induction. STUDY DESIGN: All uncomplicated pregnancies that reached 41 weeks' gestation with a Bishop score of < or = 4 were randomly assigned to one of three groups: (1) daily cervical examinations, (2) daily membrane stripping, or (3) daily placement of prostaglandin gel until 42 weeks. RESULTS: In 105 pregnancies the Bishop score on admission to labor and delivery was significantly greater in the groups receiving prostaglandin or stripping of the membranes versus the control group, whereas the converse was time of gestational age at delivery (p = 0.0001). Fewer patients required induction in the two treatment groups (20%, 17%) versus the control (69%) patients (p < 0.0001). CONCLUSIONS: Daily membrane stripping or daily placement of prostaglandin gel is successful in reducing the number of inductions at 42 weeks for postdatism.     

Aspects of fetal physiology from 18 to 37 weeks' gestation as assessed by blood sampling

OBJECTIVE: To construct reference ranges for fetal pH, oxygen pressure (PO2), and hematologic and biochemical blood constituents, which can be used to analyze changes with gestation and differences with maternal values, thus elucidating some aspects of fetal biology and the effects of the maternal and placental environments. METHODS: We assayed venous pH, PO2, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatine kinase, triglycerides, and cholesterol concentrations in 157 fetuses and 134 mothers who underwent fetal blood sampling from 18 to 37 weeks' gestation. None of the fetuses was infected or had chromosomal, hematologic, or hormonal abnormalities. RESULTS: All the variables analyzed were similar in fetuses sampled at the placental cord insertion (n = 125) or at the intrahepatic vein (n = 32). Maternal and fetal concentrations of glucose (r = 0.79, P < .001), urea (r = 0.96, P < .001), creatinine (r = 0.83, P < .001), and uric acid (r = 0.94, P < .001) correlated significantly, and their differences exhibited significant changes: the maternal-fetal differences of glucose and urea increased, whereas those of uric acid and creatinine decreased with advancing gestation. Fetal pH and PO2 decreased with gestational age, whereas hematocrit increased, similar to what has been described previously. All of the other variables, with the exception of amylase and cholesterol, changed significantly during the investigated period of pregnancy. Gestational age explained at least 40% of the variance in values of fetal total protein, pseudocholinesterase, alanine aminotransferase, creatine kinase, and triglycerides, but only 3-25% of the variation in the remainder. Most enzymes were higher in the fetus than in the maternal circulation, and all except alkaline phosphatase increased with gestational age. The maternal-fetal glucose difference correlated significantly with hematocrit, pH, and PO2, independent of gestational age and independent of each other. CONCLUSION: With the exception of aspartate aminotransferase, all of the analyzed fetal variables were different from the maternal values, and most changed with gestational age. The mechanisms leading to these fetal specificities remain mostly uncertain, but the provision of reference ranges for several blood constituents may be useful in the differential diagnosis of fetal disease.     

Heart rate variability in 1-day-old infants born at 4330 m altitude

BACKGROUND: Rates of low-birth-weight (LBW) infants are similar between Latina and white women, an epidemiologic paradox. However, few studies have analyzed the relationship between ethnicity, Latino subgroup, confounding variables, and LBW. METHODS: We analyzed 395070 singleton livebirths to Latina and non-Latina white women in California during 1992. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risks due to Latino ethnicity and Latino subgroup for very LBW (VLBW, 500-1499 g) and moderately LBW (MLBW, 1500-2499 g) outcomes. RESULTS: Latina and white women had similar unadjusted rates of VLBW (0.7% vs. 0.6%) and MLBW infants (3.7% vs. 3.4%). After adjusting for maternal age, education, birthplace, marital status, parity, tobacco use, use of prenatal care, infant sex, and gestational age, there was no difference in the odds of VLBW infants between Latina and white women (OR, 0.93 [95% CI, 0.81-1.071). Latina women had minimally elevated odds of MLBW infants (OR, 1.06 [95% CI, 1.01-1.11]) compared with white women. By Latino subgroup, there was no difference in the adjusted odds of VLBW infants among Central and South American, Cuban, Mexican, Puerto Rican, and white women. The adjusted odds of MLBW infants were elevated among Central and South American (OR, 1.14 [95% CI, 1.05-1.25]) and Puerto Rican women (OR, 1.41 [95% CI, 1.12-1.78]), relative to white women. CONCLUSIONS: The epidemiologic paradox of LBW in Latinos is valid. New conceptual models are needed to identify Latina women who are at risk for adverse pregnancy outcomes.     

Perinatal and neonatal outcome and late pulmonary sequelae in infants born after preterm premature rupture of membranes

The regulation of the lytic and lysogenic development in the life cycle of bacteriophage Mu is regulated in part by its repressor, c, which binds to three operator sites, O1, O2 and O3, overlapping two divergent promoters. The oligomeric structure of this repressor protein was investigated by hydrodynamic and biochemical methods. Size-exclusion chromatography, analytical ultracentrifugation, dynamic light scattering, crosslinking and direct electron microscopy observations suggest that c exists primarily as a hexamer with a molecular mass of 120-140 kDa at low concentrations, i.e. in the 10-microM range. This molecule undergoes a self-assembly process leading to dodecamers and higher order species as the concentration is further increased in a manner depending on the nature of the solvent. Our results also suggest that these species have an elongated structure, and a possible arrangement of the subunits within the hexamer is proposed. The implication of this unusual quaternary structure for a repressor in its interaction with the operator sites O1 and O2 remains to be elucidated.     

Twenty-month outcome in ventilator-dependent, very low birth weight infants born during the early years of dexamethasone therapy

We sought to examine the effect of the introduction of dexamethasone therapy on health, growth, and neurodevelopmental outcome in very low birth weight (VLBW) infants at 20 months of age. We compared outcomes in all 86 VLBW infants (mean birth weight 871 gm, mean gestational age 26.4 weeks) who were ventilator dependent on day 21 of life during the 2 years preceding October 1988 (period 1), when dexamethasone therapy became accepted clinical practice in our unit, with outcomes in all 124 infants (mean birth weight 891 gm, mean gestational age 26.9 weeks) with similar ventilator status during the subsequent 2 years (period 2). In addition, we compared outcomes in infants who received dexamethasone during period 2 with those in a concurrent cohort of less ill infants who were not given dexamethasone. There were no significant differences between periods 1 and 2 in mortality rates after 21 days (17% vs 21%), need for home oxygen (23% vs 25%), oxygen dependence at 20 months of corrected age (11% vs 10%), rate of neurosensory impairment (24% vs 25%), and mean Bayley Mental scores (81.5 vs 77.2) or Psychomotor Development Index (81.6 vs 71.1). Infants who received dexamethasone during period 2 had significantly more severe lung disease and poorer respiratory, growth, and developmental outcomes. We conclude that VLBW infants with ventilator-dependent chronic lung disease have very poor outcomes, even when treated with dexamethasone. More information is needed from prospective, randomized trials before dexamethasone can be accepted as routine therapy for chronic lung disease.     

Developmental and food profiles of infants born to adolescent and adult mothers

OBJECTIVE: To compare developmental markers and dietary intake of infants born to lower socioeconomic adolescent and adult mothers. DESIGN: Sixty-one adolescent (age 14-18 years) and 60 adult (age 22-28 years) mothers met inclusion criteria of comparable socioeconomic status, age range, urban/rural residence, and distribution of infants by gender. SAMPLE/SETTING: Adolescent subjects were recruited in last trimester and adult mothers postpartum. Interviews were conducted when infants were about 6 and 12 months of age. Data included age of occurrence for eight markers, age at adding complementary foods, two 24-h dietary recalls, and two measurements of growth. RESULTS: Adolescent mothers reported a significantly earlier age at which the infant "holds a spoon by self" and "drinks alone from a trainer cup." Six other markers were not significantly different between groups. Adolescent mothers fed cereal significantly earlier than did adult mothers, but there were no significant differences for fruit, vegetables, and meat. At 12 months, infants of adolescents had intakes of vitamin D and iron which were < 100% of recommended allowances, as did infants of adult mothers for vitamin D, iron, and zinc. Dietary fat was significantly higher at 6 and 12 months and vitamin C was lower at 12 months for infants of adolescents compared to the adult group. CONCLUSIONS: Compared to adult mothers, adolescent mothers reported earlier mean ages for developmental markers related to self-feeding, and introduced cereal earlier. In each group, selected nutrient intakes decreased from recommended amounts in the 6-12-month period. Fat intakes were significantly different between groups at 6 and 12 months.