Single dose fetal betamethasone administration stabilizes postnatal glomerular filtration rate and alters endocrine function in premature lambs

These studies determined the effects of fetal treatment with betamethasone alone, or in combination with thyroid hormone (thyroxine; T4), on postnatal renal and endocrine adaptations in preterm newborn lambs. Ovine fetuses (126 d of gestation; term = 150 d) received single, ultrasound-guided intramuscular injections of saline, 0.5 mg/kg betamethasone (Celestone Soluspan, or 0.5 mg/kg betamethasone plus 60 micrograms/kg T4. After 48 h, lambs were delivered, treated with surfactant (Survanta, 100 mg/kg), and ventilated for 3 h. Due to maintained urine flow in the betamethasone-treated animals and a significant decrease in the saline group, betamethasone versus saline urine flow values (0.11 +/- 0.03 versus 0.03 +/- 0.004 mL.min-1.kg-1) were significantly elevated by the end of studies. GFR (1.5 +/- 0.3 versus 0.8 +/- 0.2 mL.min-1.kg-1) and mean blood pressure (61 +/- 4 versus 42 +/- 3 mm Hg) values also were higher in the betamethasone-treated animals. Although renal blood flow, renal plasma flow, and fractional sodium excretion rates did not differ, betamethasone versus saline values for the filtration fraction (11.9 +/- 1.5 versus 7.4 +/- 1.5%) and total sodium reabsorption (196 +/- 38 versus 81 +/- 16 microEq.min-1.kg-1) were increased. Betamethasone versus saline treatment also was associated with significant reductions in plasma angiotensin II (125 +/- 23 versus 550 +/- 140 pg/mL) and AVP (116 +/- 19 versus 230 +/- 77 pg/mL) levels. Overall, the effects of combined betamethasone + T4 treatment were similar to the effects of betamethasone alone. Conclusions: 1) fetal betamethasone injection 48 h before delivery stabilizes GFR and significantly alters endocrine function in preterm newborn lambs, and 2) the addition of T4 does not augment betamethasone-induced renal and endocrine responses.     

Minimum interval from fetal betamethasone treatment to postnatal lung responses in preterm lambs

OBJECTIVE: We hypothesized that fetal betamethasone exposure for < 24 hours would improve postnatal lung function in preterm lambs. STUDY DESIGN: Singleton fetal sheep were randomized to receive by ultrasonographically guided fetal injections of 0.5 mg/kg betamethasone or saline solution either 8 or 15 hours before preterm delivery and postnatal assessment of lung function. RESULTS: After the 15-hour fetal treatment-to-delivery interval, betamethasone-treated lambs had twofold improvement in compliance and lung volumes, a fourfold to fivefold decrease in edema index, and higher blood pressures than saline solution-treated lambs. Postnatal lung function or lung volumes did not improve for the 8-hour treatment-to-delivery interval, although betamethasone decreased the pulmonary edema and increased the postnatal blood pressure. CONCLUSIONS: The minimal interval from fetal exposure to corticosteroids to delivery for improved postnatal lung function was between 8 and 15 hours. Corticosteroid effects on pulmonary edema and blood pressure occurred within 8 hours.     

Effects of fetal corticosteroid treatments on postnatal surfactant function in preterm lambs

Effects of prenatal corticosteroid on the properties of surfactant have not previously been evaluated. A single ultrasound-guided fetal injection with 0.5 mg/kg betamethasone 48 h before delivery of preterm lambs at 134- to 135-days gestation improved oxygenation, lowered the ventilatory pressures required to maintain arterial PCO2 between 30 and 40 Torr and decreased the protein leak of albumin from the intravascular to the alveolar space. This dose of glucocorticoid did not alter surfactant-saturated phosphatidylcholine pool sizes in the airspaces of preterm lambs. However, the treatment changed the characteristics of the surfactant recovered from the ventilated preterm lambs. The in vitro conversion from heavy to light subtype surfactant decreased from 59% for the saline-treated lambs to 37% for the corticosteroid-treated lambs after 180 min of surface area cycling (P < 0.02). Surfactant from the corticosteroid-treated lambs also increased the dynamic compliance of preterm surfactant-deficient rabbits more than did surfactant from the saline-treated lambs (P < 0.05). Prenatal treatment of preterm lambs with betamethasone improved the functional characteristics of surfactant without significant effects on the alveolar surfactant pool sizes.     

Risk factors for aboriginal low birthweight, intrauterine growth retardation and preterm birth in the Darwin Health Region

Risk factors for Aboriginal low birthweight (< 2500 g), preterm birth (< 37 weeks' gestation) and intrauterine growth retardation (under the tenth percentile of Australian birthweights for gestational age) were examined in 503 live-born singletons recorded as born to an Aboriginal mother and routinely delivered at the Royal Darwin Hospital between January 1987 and March 1990. Infants born to mothers with body mass index less than 18.5 kg/m2 had five times the risk of having low birthweight and 2.5 times the risk of intrauterine growth retardation. Population-attributable risk percentages suggest that 28 per cent of low birthweight and 15 per cent of growth retardation could be attributed to maternal malnutrition. Risk percentages for maternal smoking of more than half a packet of cigarettes a day were 18 per cent for low birthweight and 10 per cent for growth retardation. For growth retardation, 18 per cent could be attributed to a maternal age under 20 years. Risk factors for preterm birth were predominantly obstetric: the population-attributable risk percentage for pregnancy-induced hypertension was 26 per cent and for other obstetric conditions was 16 per cent. For Aboriginal births in the Darwin Health Region, maternal malnutrition and smoking are key elements in the prevention of low birthweight and intrauterine growth retardation. Teenage pregnancy is an important risk for intrauterine growth retardation, and pregnancy-induced hypertension is a risk for preterm birth.     

Levels of immunoglobulin E (IgE) in paired examinations of serum and synovial fluid in rheumatoid arthritis and reactive synovitis of local origin

Twenty-eight pregnant patients exhibiting subnormal fetal growth patterns by serial ultrasonic cephalometry were studied. Only 12 (43%) delivered small-for-gestational-age (SGA) infants indicating a poor correlation between the prenatal assessment of intrauterine growth retardation (IUGR) by ultrasonic cephalometry and the neonatal evaluation of the newborn as SGA. The most important factors in the evaluation of the fetus with subnormal serial ultrasonic cephalometry were: 1) the type of ultrasonic growth pattern ("late flattening" vs "low growth profile"), 2) the presence or absence of maternal high-risk factors, and 3) the gestational age of the fetus at the time of detection of the growth abnormality. A pregnancy showing a late flattening type of growth pattern by serial ultrasound in the presence of maternal high-risk factors and with the growth abnormality being detected before 35 weeks of gestation, almost certainly will terminate with the birth of a SGA infant. On the contrary, serial plasma free estriol determinations were not useful in predicting the fetal status at birth. All but 4 of these patients were delivered at term and there was neither perinatal mortality nor significant morbidity. It is suggested that the existence of an abnormal cephalometric pattern is not an indication for early delivery unless fetal distress is detected by means of an oxytocin challenge test.     

Antenatal betamethasone therapy augments isoproterenol and prostaglandin E2-mediated relaxation of preterm ovine pulmonary veins

Antenatal glucocorticoid therapy improves pulmonary function in preterm newborns. We have determined the effect of antenatal glucocorticoid therapy on isoproterenol and prostaglandin (PG) E2-mediated relaxation in preterm ovine pulmonary veins after birth. Ovine fetuses (121 and 126 d of gestation; term = 150 d) received an ultrasound guided intramuscular injection of betamethasone, 0.5 mg/kg, or saline. Lambs were delivered 15 or 48 h later, ventilated for 3 h, and killed. Isolated fourth generation pulmonary veins were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2, 5% CO2) at 37 degrees C, and their isometric tension was recorded. During contractions to U46619, isoproterenol and PGE2 induced greater relaxations of pulmonary veins of betamethasone-treated lambs than those of control. Forskolin, an activator of adenylate cyclase, caused greater relaxation in veins of betamethasone-treated lambs than in those of controls. A greater relaxation of veins treated with betamethasone than that of control veins also occurred in the presence of isobutylmethylxanthine, an inhibitor of phosphodiesterases. All vessels relaxed similarly to 8-bromo-cAMP, a cell membrane-permeable analog of cAMP. When stimulated with isoproterenol, PGE2, and forskolin, adenylate cyclase activity of crude membrane preparations of pulmonary veins treated with betamethasone was greater than that of controls. These results demonstrate that antenatal betamethasone therapy potentiates isoproterenol and PGE2-mediated relaxation of pulmonary veins of preterm lambs; an enhanced adenylate cyclase activity explain in part the effect of antenatal glucocorticoid therapy on pulmonary veins of preterm lambs.     

In vivo efficacy of silver-coated (Silzone) infection-resistant polyester fabric against a biofilm-producing bacteria, Staphylococcus epidermidis

OBJECTIVE: To study the characteristics of birthweight and gestational age of third trimester fetal deaths which occurred before the onset of labour. DESIGN: Review of computerised confidential perinatal mortality records. Data originated from the 1992 Trent Region Perinatal Mortality Survey. SAMPLE: One hundred and forty-nine antepartum stillbirths of at least 24 weeks of gestation confirmed by early ultrasound scan. Congenital abnormalities and multiple pregnancies were excluded. MAIN OUTCOME MEASURES: Reported causes of stillbirth; weight-for-gestational age centiles based on a standard derived from normal pregnancies; pregnancy characteristics compared with the local maternity population. RESULTS: Of 149 stillbirths, 83 (56%) were preterm and 66 were at term, and the majority (126; 85%) occurred from 31 weeks. Most of the deaths (97; 65%) were reported as 'unexplained' even though post-mortems had been carried out in 60% of all cases. Using a gestational age-specific fetal weight standard derived from normal, term live births, 41% of all cases of stillborn infants were small-for-gestational age (< 10th centile; OR 6.2; 95% CI 3.3-11.5); 39% of which had been classified as unexplained were small for gestational age (OR 5.6; 2.6-12.0). This excess of small stillbirths was most pronounced between 31 and 33 weeks, where the weights of 63% of all stillbirths and 72% of unexplained fetal deaths were < 10th centile. Overall, a higher proportion of preterm (< 37 weeks) than term stillbirths were small for gestational age: 53% vs 26% (OR 3.3; 1.6-6.5). However, at term there were also more subtle differences in weight deficit, with more fetuses with a weight between the 10th and 50th centiles than between 50th and 90th (36 vs 11; OR 3.3; 1.4-7.8). Mothers of pregnancies ending in stillbirth were similar in age, size, parity and ethnic group to mothers of live born babies, but were more likely to be smokers (37 vs 27%, OR 1.6; 1.2-2.3). CONCLUSIONS: Many stillborn babies are small for gestational age. In the absence of significant differences in physiological pregnancy characteristics, this is unlikely to be a constitutional smallness, but represents a preponderance of intrauterine growth restriction. For a full appreciation of the strength of this association, appropriate weight standards and classifications need to be applied in perinatal mortality surveys. Many antepartum stillbirths which are currently designated as unexplained may be avoidable if slow fetal growth could be recognised as a warning sign.     

Characterization of fetal ovine renal dysplasia after mid-gestation ureteral obstruction

OBJECTIVE: The etiology and pathogenesis of renal dysplasia are poorly understood. To characterize the histologic changes in fetal renal dysplasia, we studied a fetal ovine model of urinary obstruction. DESIGN: Animal study. ANIMALS: Seven fetal lambs, and other lambs of the same gestational age as controls. INTERVENTIONS: Unilateral ureteral ligation on fetal lambs at approximately 70 days' gestation (term for sheep is 145 days), during nephrogenesis. Kidneys were subsequently collected, examined histologically and characterized by immunohistochemical tests involving cytokeratin antiserum and a monoclonal antibody to alpha-actin. OUTCOME MEASURES: Histologic changes in ligated fetal lamb kidneys, based on comparison with normal fetal lamb kidneys. RESULTS: At near term (140 days' gestation), the ligated kidney showed distorted and less abundant renal parenchyma than a normal control kidney. Upon microscopic examination, the ligated kidney displayed marked architectural distortion of the outer cortex, with abundant interstitial fibrosis, primitive ductules and glomeruli, and cysts of varying sizes lined by squamous and cuboidal epithelia and surrounded by a loose mesenchyme. The renal medulla contained differentiated collecting ducts, which were structurally distorted and less abundant than in normal control kidneys. The proximal and distal tubule elements were primitive and markedly underdeveloped. Cytokeratin immunoreactivity was present in the collecting duct epithelium and in the cuboidal epithelium lining many of the cortical cysts. Smooth muscle alpha-actin immunoreactivity was localized in the cortical region of the kidney, which highlighted the abundance and disorganization of the undifferentiated mesenchyme and identified the fibromuscular collars of the primitive ductules of the cortex and the distorted collecting ducts of the medulla. CONCLUSIONS: These results highlight the histologic changes resulting from unilateral ureteral ligation in fetal lambs. This model is useful in the study of the pathogenesis of fetal obstructive renal dysplasia.     

Evidence of participation of the soluble tumor necrosis factor receptor I in the host response to intrauterine infection in preterm labor

PROBLEM: This study was conducted to determine whether: (1) the soluble tumor necrosis factor receptor I (sTNF-rI) is present in human amniotic fluid, neonatal urine, and the feto-maternal plasma; (2) there are changes in the concentration of the sTNF-rI in amniotic fluid with gestational age; and (3) microbial invasion of the amniotic cavity (in term and preterm parturition) is associated with changes in amniotic fluid sTNF-rI concentrations. METHOD: Amniotic fluid was retrieved by amniocentesis from 185 women classified into 11 groups according to gestational age (midtrimester, preterm gestation, and term), the presence or absence of labor, spontaneous rupture of membranes and microbial invasion of the amniotic cavity. sTNF-rI was assayed with a sensitive and enzyme-linked immunosorbent assay (ELISA) validated for amniotic fluid. In addition, sTNF-rI concentrations were determined in fetal blood obtained by cordocentesis in preterm gestations (N = 24) or at the time of delivery after spontaneous labor at term (N = 10). sTNF-rI concentrations were also measured in maternal venous and cord blood and neonatal urine (n = 13). RESULTS: sTNF-rI was found to be present in all amniotic fluid samples, maternal blood and fetal blood and neonatal urine samples; sTNF-rI concentrations were higher in the midtrimester than at term (mean +/- SD: 36.2 +/- 12.2 ng/ml versus mean +/- SD: 5.56 +/- 5.72 ng/ml [P < .05]); patients with preterm labor and microbial invasion of the amniotic cavity (with intact or with ruptured membranes) had significantly higher amniotic fluid concentrations of sTNF-rI than patients without microbial invasion; in the absence of microbial invasion, parturition (both term and preterm) was not associated with changes in amniotic fluid concentrations of sTNF-rI; neonatal urine contained the highest concentrations of sTNF-rI of all biological fluids assayed including maternal and neonatal/fetal blood and amniotic fluid. CONCLUSIONS: It was concluded that sTNF-rI is a physiologic constituent of amniotic fluid, as well as of the fetal and maternal plasma; that amniotic fluid sTNF-rI concentrations decrease as a function of gestional age and increases in the concentration of the sTNF-rI are part of the host response to intrauterine infection in preterm parturition.     

Preterm and term births of small for gestational age infants: a population-based study of risk factors among nulliparous women

OBJECTIVE: To study risk factors for small for gestational age (SGA) infants by gestational age among nulliparous women and to estimate mortality rates among SGA and appropriate-for-gestational-age (AGA) infants by gestational age. DESIGN: A population-based study from the Swedish Medical Birth Register. Setting Sweden 1992 1993. POPULATION: Liveborn singleton infants to nulliparous women (n = 96,662). MAIN OUTCOME MEASURES: Crude and adjusted odds ratios of risk factors for SGA by gestational age. Rates of neonatal and postneonatal mortality. RESULTS: Older maternal age (> or = 30 years) was foremost associated with increased risks of very and moderately preterm SGA (> or = 32 weeks and 33-36 weeks, respectively), but also with term SGA (> or = 37 weeks). Risks of SGA increased with decreasing maternal height at all gestational ages. Smoking increased the risks of moderately preterm and term SGA. Short maternal education increased the risk of preterm SGA and low pre-pregnancy body mass index slightly increased the risk of term SGA. Pre-eclampsia and essential hypertension foremost increased the risk of very preterm SGA (OR = 40.5 and 32.4, respectively) and moderately preterm SGA (OR = 17.4 and 10.6, respectively), but also increased the risk of term SGA. Neonatal and postneonatal mortality rates of SGA infants were substantially influenced by gestational age, and mortality rates were consistently higher among preterm SGA infants compared with AGA infants. Conclusions: Risk factors for SGA and mortality rates among SGA infants vary by gestational age. A subdivision of risk factors by gestational age adds knowledge, particularly about risks of preterm SGA, where the highest rates of mortality were observed.     

Determinants of poor pregnancy outcomes among teenagers in Sweden

OBJECTIVE: To study pregnancy outcomes among teenagers and to determine whether age-related increases in risk are due to differences in socioeconomic conditions, maternal smoking, or anthropometric status. METHODS: All single births during 1990-1991 to mothers aged less than 25 years recorded in the Swedish Medical Birth Registry were studied (n = 62,433). The pregnancy outcomes analyzed were late fetal death, infant mortality, preterm birth, low birth weight, small for gestational age, and low Apgar scores. Information on maternal age, parity, family situation, maternal smoking, maternal height, and weight gain during pregnancy was recorded in the Medical Birth Registry. Information on socioeconomic characteristics was obtained from the Population Census. Logistic regression analysis was used to define the determinants of the adverse outcomes among teenagers. RESULTS: Compared with women aged 20-24 years, girls of 17 years or less were at higher risk for preterm birth (odds ratio [OR] 1.6), and this increased risk remained essentially unchanged after controlling for major confounding factors (OR 1.5). Teenagers also had a crude 50% higher risk of late fetal death and infant mortality, but this risk was reduced after controlling for the effect of socioeconomic characteristics (adjusted OR 1.2). CONCLUSIONS: The increase in risk of late fetal death and infant mortality associated with low maternal age is substantially an effect of teenagers' poorer socioeconomic situation. However, the increase in preterm birth among younger teenagers suggests that young maternal age may be a biologic risk factor for preterm birth.     

Estimation of the developmental age of the ovine fetus and lamb

Fifty-six fetuses and 33 lambs were obtained from a flock of ewes at set gestational intervals between 50 to 180 days after conception. The fetuses and lambs were killed, disected and the sizes and weights of a wide range of skeletal and soft tissues were measured. Five morphological parameters emerged as most suitable for the determination of normal foetal developmental age. By plotting the mean value and ninety-five per cent tolerance limits, the rates of growth and the variability of each parameter were studied. Crown-anus length is useful for determining fetal developmental age from 50 to 100 days gestation; brain weight, long bone length and the number of appendicular ossification centres can be used to determine fetal development age from 50 days gestation until term.     

Dexamethasone and fetal heart rate variation

OBJECTIVE: To determine the effect of maternal administration of dexamethasone on fetal heart rate and its variation. DESIGN: Retrospective analysis of computerised data derived from cases studied over three years. SETTING: High risk pregnancy unit, John Radcliffe Hospital, Oxford. SUBJECTS: Twenty-eight pregnant women, at 27 to 32 weeks of gestation, to whom dexamethasone was given to accelerate pulmonary maturation in the expectation of preterm delivery. METHODS: Dexamethasone (two doses of 12 mg intramuscularly, 12 h apart) was given on 51 occasions at weekly intervals (one to four occasions per patient). Complete data were available for cardiotocograph analysis from computerised measurement of fetal heart rate variables for two days before and four days after dexamethasone and, in 19 women, measurements of umbilical arterial flow velocity waveforms before and after dexamethasone. RESULTS: In 10 pregnancies without fetal distress there was a highly significant (P < 0.01) transient rise in short term fetal heart rate variation after dexamethasone administration, from means (SE) 6.4 (0.28) to 9.8 (0.4) ms. In 18 pregnancies with subsequent delivery for fetal distress (abnormal fetal heart rate pattern) and high umbilical arterial resistance index [mean 0.93 (0.06 SE)], the rise in short term fetal heart rate variation was less (P < 0.01), from mean (SE) 5.4 (0.26) to 6.1 (0.48) ms. In a further case of discordant twin pregnancy, the larger twin continued to respond to dexamethasone administrations with a rise in fetal heart rate variation for five weeks; the smaller twin, with maintained tachycardia and reduced umbilical arterial end-diastolic flow velocity, failed to respond after the first two weeks. CONCLUSION: The results show that maternal dexamethasone administration normally causes a rise in fetal heart rate variation for up to a day. This rise is reduced in pre-eclampsia or intrauterine growth retardation, associated with a reduction in umbilical flow, perhaps because of a consequential lower concentration of steroid in the fetus. The results contrast with those for betamethasone which has been reported to reduce fetal heart rate variation.     

Human herpesvirus-6: a new member of the herpesvirus family, a threat to AIDS, organ-transplanted and other immune deficient patients

OBJECTIVE: The purpose was to evaluate a low weight to length ratio as a correlate of perinatal morbidity and mortality. STUDY DESIGN: Data from the Collaborative Perinatal Project for infants of 34 weeks' gestation or more were evaluated. Associations between the weight to length ratio of < 10% (low weight to length) and birth weight of < 10% (small for gestational age) by gestational age and gender, perinatal depression, dysmaturity, cerebral palsy, and neonatal mortality were evaluated. RESULTS: A low weight to length ratio and small for gestational age status were associated with most markers of perinatal morbidity and mortality in term and preterm infants. In infants not small for gestational age, a low weight to length ratio was associated with increased morbidity and mortality (relative risk of 1.9 to 4.2) in term infants, and with perinatal depression (relative risk of 2.9) in preterm infants. Logistic regression found low weight to length ratio was a better independent correlate than small for gestational age status for all markers assessed and found low weight to length ratio was significantly associated with all morbidity and mortality markers in infants not small for gestational age. CONCLUSION: Low weight to length ratio, a marker for asymmetric growth restriction, is correlated with perinatal morbidity, even in infants not small for gestational age.     

Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older

We analysed the results of oocyte donation to women of advanced reproductive age (> or = 45 years old) and followed their pregnancies through to delivery in order to assess obstetrical outcomes. Patients (n = 162) aged 45-59 years (mean +/- SD; 47.3 +/- 3.4 years) underwent 218 consecutive attempts to achieve pregnancy. Oocytes (16.2 +/- 7.2 per retrieval) were provided by donors < or = 35 years old. Cleaving embryos (8.2 +/- 4.8 zygotes/couple) were transferred transcervically (4.5 +/- 1.1 per embryo transfer) to recipients prescribed oral micronized oestradiol and intramuscular progesterone. Following oocyte aspiration there were six instances of non-fertilization (2.8%) and 212 embryo transfers. A total of 103 pregnancies was established for an overall pregnancy rate (PR) of 48.6%, which included 17 preclinical pregnancies, 12 spontaneous abortions, and 74 delivered pregnancies (clinical PR 40.6%; delivered PR 34.9%). Multiple gestations were frequent (n = 29; 39.2% of pregnancies) and included 20 twins, seven triplets, and two quadruplets. Two of the triplet and both of the quadruplet pregnancies underwent selective reduction to twins. Antenatal complications occurred in 28 women (37.8% of deliveries) and included preterm labour (n = 9), gestational hypertension (n = 8), gestational diabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia (n = 2), HELLP syndrome (n = 2), and fetal growth retardation (n = 2). 48 (64.8%) deliveries were by Caesarean section. The gestational age at delivery for singletons was 38.3 +/- 1.3 weeks (range 35-41 weeks), with birth weight 3218 +/- 513 g (range 1870-4775 g); twins 35.9 +/- 2.0 weeks (range 32-39 weeks), birth weight 2558 +/- 497 g (range 1700-3450 g); and triplets 33.5 +/- 0.7 weeks (range 32-34 weeks), birth weight 1775 +/- 190 g (range 1550-2100 g). Neonatal complications (4.6% of babies born) included growth retardation (n = 2), trisomy 21 (n = 1), ventricular septal defect (n = 1), and small bowel obstruction (n = 1). There were no maternal or neonatal deaths. We conclude that oocyte donation to women of advanced reproductive age is highly successful in establishing pregnancy. However, despite careful antenatal screening, obstetrical complications are common, often secondary to multiple gestation.     

Human recombinant anti-Rh(D) monoclonal antibodies: improvement of biological properties by in vitro class-switch

The aim of this study was to investigate how intrauterine growth retardation affects body proportions in VLBW infants. The cohort consisted of 135 surviving and 80 deceased preterm infants weighing less than 1250 grams at birth. Gestational age varied between 24 and 36 weeks (mean age 29.7 and 27.5 weeks, respectively). Birth weight was more than 2 SD below the mean birth standard values in 32% of the surviving, and in 27% of the deceased infants. Reduction of weight, length and head circumference at birth was analysed using Z scores based on Swedish birth standards. Z scores of weight, length and head circumference were highly correlated in the surviving and the deceased infants (r = 0.78 to 0.94 and 0.65 to 0.97, respectively). Length was significantly more affected by growth retardation than weight. Weight and head circumference were proportionately reduced. Intrauterine growth retardation influences body proportions in VLBW infants differently than in larger preterm and term infants.     

Diagnosis of phenylketonuria in a 35-year-old mother in relation to prenatal diagnosis of intrauterine growth retardation with microcephaly

BACKGROUND: Some French pregnant women with phenylketonuria (PKU), born before 1978, have not been tested with the Guthrie method during the neonatal period. They have a risk of spontaneous abortion and their infants are often mentally retarded with microcephaly and/or congenital heart anomaly. CASE REPORT: A woman with a moderate mental retardation became pregnant at the age of 31 years. Her newborn had a severe intrauterine growth retardation with microcephaly and developed mental retardation. This mother became pregnant again 4 years later. Repeated fetal ultrasonography showed progressive growth retardation. Maternal blood phenylalanine concentration was 18 mg/100 mL. Therapeutic abortion at 27 weeks of gestational age showed a fetus with several abnormalities, particularly cardiovascular and cerebral. CONCLUSION: It is still possible to meet women with unrecognized atypical PKU. Fetus or infant born with unexplained growth retardation and microcephaly requires search for maternal PKU.     

Preterm delivery: effects of socioeconomic factors, psychological stress, smoking, alcohol, and caffeine

OBJECTIVE: To examine the relation between preterm birth and socioeconomic and psychological factors, smoking, and alcohol, and caffeine consumption. DESIGN: Prospective study of outcome of pregnancy. SETTING: District general hospital in inner London. PARTICIPANTS: 1860 consecutive white women booking for delivery; 1513 women studied after exclusion because of multiple pregnancy and diabetes, refusals, and loss to follow up. MEASUREMENTS: Gestational age was determined from ultrasound and maternal dates; preterm birth was defined as less than 37 completed weeks. Independent variables included smoking, alcohol and caffeine consumption, and a range of indicators of socioeconomic status and psychological stress. MAIN RESULTS: Unifactorial analyses showed that lower social class, less education, single marital status, low income, trouble with "nerves" and depression, help from professional agencies, and little contact with neighbours were all significantly associated with an increased risk of preterm birth. There were no apparent effects of smoking, alcohol, or caffeine on the length of gestation overall, although there was an association between smoking and delivery before 32 weeks. Cluster analysis indicated three subgroups of women delivering preterm: two predominantly of low social status and a third of older women with higher social status who did not smoke. Mean gestational age was highest in the third group. CONCLUSIONS: Adverse social circumstances are associated with preterm birth but smoking is not, apart from an association with very early births. This runs counter to findings for fetal growth (birth weight for gestational age) in this study, where a strong effect of smoking on fetal growth was observed but there was no evidence for any association with psychosocial factors.     

Quantitative study on the effect of osthole on proximal tibiae in ovariectomized (OVX) rats

OBJECTIVE: To determine if a correlation exists between the level of maternal serum alpha-fetoprotein (MSAFP) elevation and the rate of adverse pregnancy outcome, to examine the timing of pregnancies ending in fetal or neonatal death, and to develop a protocol for antepartum surveillance in an effort to prevent these adverse outcomes. STUDY DESIGN: Singleton pregnancies with a single second-trimester elevated MSAFP > or = 2.0 multiples of the median (MoM) were eligible if a targeted ultrasound evaluation (< 24 weeks) was in agreement with the dates and no fetoplacental anomaly was detected. Three groups were established based on the second-trimester MSAFP elevation: 2.0-2.49, 2.5-2.99 and > or = 3.0 MoM. RESULTS: Among the 383 patients enrolled, delivery data were available on 333 infants. Stratified by MSAFP elevations of 2.0-2.49, 2.5-2.99 and > or = 3.0 MoM, the rates of adverse pregnancy outcome were: (1) preterm birth: 14.3%, 15.6%, 20.3%; (2) small for gestational age at birth: 7.4%, 11.1%, 22.2%; and (3) perinatal deaths (neonatal and fetal): 2.6%, 3.3%, 5.6%. Seven pregnancy losses (three neonatal and four fetal deaths) occurred prior to 28 weeks. Of these seven, six fetuses exhibited intrauterine growth retardation by 23-26 weeks' gestation, and five of six were associated with MSAFP levels > or = 2.5 MoM. Four losses (two neonatal and two fetal deaths) occurred after 28 weeks. Of these, three involved structurally normal infants with normal growth who died after 34 weeks. All three of these pregnancies exhibited MSAFP elevations < 2.5 MoM. CONCLUSION: In pregnancies with an unexplained elevated second-trimester MSAFP, the rate of adverse pregnancy outcomes is increased with higher elevations. Any proposed program to improve pregnancy outcome in patients with unexplained MSAFP elevations must include efforts aimed at preventing preterm delivery, repeat ultrasound at 24-26 weeks to rule out early-onset intrauterine growth retardation in pregnancies with elevations > or = 2.5 MoM and fetal biophysical monitoring, even in normally grown fetuses, instituted at 32 weeks to detect fetuses at risk for intrauterine death.