[Systemic lupus erythematosus and antiphospholipid syndrome: How to manage pregnancy?]. / Lupus systémique et syndrome des antiphospholipides : comment prendre en charge la grossesse ?

Pregnancy in systemic lupus erythematosus patients is a common situation that remains associated with higher maternal and fetal mortality/morbidity than in the general population. Complications include lupus flares, obstetrical complications (fetal loss, in utero growth retardation, prematurity) and neonatal lupus syndrome. The association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetrical complications. Improving the care of these pregnancies depends upon a systematic pregnancy planning, ideally during a preconception counseling visit and a multidisciplinary approach (internist/rheumatologist, obstetrician and anesthetist). The absence of lupus activity, the use of appropriate medications during pregnancy adjusted to the patient's medical history and risk factors, and a regular monitoring are the best tools for a favorable outcome for these high-risk pregnancies. The aim of this review article is to perform an update on the medical care of pregnancy in systemic lupus erythematosus or antiphospholipid syndrome to reduce the risk of complications and to ensure the best maternal and fetal prognosis.

High levels of P-glycoprotein activity in human lymphocytes in the first 6 months of life.

P-glycoprotein (P-gp) is an efflux transporter that controls the intracellular concentrations of drugs. Human development may modulate P-gp function. We investigated the effect of age on P-gp activity and MDR1 gene expression in lymphocytes. We also assessed the influence of human immunodeficiency virus (HIV) infection. We used 3,3'-diethyloxacarbocyanin iodide (DiOC(6)) efflux, estimated by flow cytometry, to quantify P-gp activity in 94 children (age range, 0-18 years) and 25 adults. MDR1 gene expression was quantified using reverse transcription-PCR (RT-PCR). In T and natural killer (NK) cell populations, P-gp activity peaked at birth, decreased between the ages of 0 and 6 months, and stabilized between the ages of 6 months and 2 years (P < 10(-6)). These maturation profiles were also strongly correlated (r = 0.67, P < 10(-6)). HIV infection did not affect P-gp activity in the lymphocytes of children. MDR1 gene expression was not influenced by age, nor was it correlated with P-gp activity. The high levels of P-gp activity observed in the lymphocytes of children ~6 months of age may affect the efficacy of intracellular drugs.

First-trimester ultrasound diagnosis of skeletal dysplasia associated with increased nuchal translucency thickness.

A series of five cases of skeletal dysplasia is reported in which the diagnosis was reached at the 11-14-week routine ultrasound examination in our referral center. All five cases had increased nuchal translucency thickness (NT) associated with bone abnormalities. We review the current literature on skeletal dysplasia in the first trimester of pregnancy associated with increased NT.

[Effect of smoking on mode of delivery and per partum hypoxia and acidosis]. / Conséquences foetales du tabagisme sur les modes d'accouchement, l'hypoxie et l'acidose per-partum.

METHODS: We conducted a PubMed research using the following key words: fetal, smoking, distress, hypoxia, acidosis, heart rate, cesarean. RESULTS: The different combinations of key works allowed selection of 251 since 1967. Several article were addressed directly to the question raised; two for meconial fluid alone. One article detailed possible method biases. Several articles detailed the Apgar score in newborns of smoking mothers. Three calculated the risk of cesarean section in smokers. CONCLUSION: Data in the literature is not sufficient to argue in favor of an association between fetal asphyxia during labor and smoking. Only one study showed a higher rate of cesarean section in mothers smoking more than 10 cigarettes per day. Nevertheless, the Apgar score does not appear to be modified by moderate maternal smoking. Paradoxically, maternal smoking could have a protective effect on meconial aspiration and could have a moderately reducing effect on the rate of cesarean section during labor in patients smoking less than 10 cigarettes per day via lower fetal weight. These findings should be examined with caution because they still need to be confirmed and do not take into consideration other adverse effects of smoking on the fetus.

[Dating biometry with crown-rump length, precision of a routine practice]. / Précision de la biométrie de datation à l'échographie du premier trimestre dans la pratique courante.

OBJECTIVE: The goal of this study was to determine the accuracy of an everyday practice for assessing gestational age by ultrasound and redefine the correction of gestational age policy. MATERIALS AND METHODS: This study used first trimester measurements taken during a three-year period. We considered all births from pregnancies that began by an in vitro fertilization procedure. We examined 143 consecutive files containing 257 measurements made by 72 different operators. We applied two reference curves to calculate the date the pregnancy began and the centiles of the prediction interval for +/- 7, +/- 5 and +/- 3 days. RESULTS: The prediction intervals for +/-7, +/-5, +/-3 days excluded 2%, 6%, and 25% respectively of the embryos from one of the two reference curves. These intervals were 1%, 5% and 20%, were better for the other curve. CONCLUSION: Correction of gestational age has to take into consideration variations in the embryo length. We correct the gestational age only if the difference with ultrasound assessment is more than one week.

Congenital erythropoietic porphyria (Günther's disease): two cases with very early prenatal manifestation and cystic hygroma.

Congenital erythropoietic porphyria (CEP) or Günther's disease is the rarest form of the porphyrias. The disease is usually diagnosed at birth or during early infancy, but rarely in utero. We describe here the first two cases of very early prenatal expression of CEP with cystic hygroma diagnosed at 14 weeks in the first fetus and at 19 weeks in the second. Both fetuses presented with severe nonimmune hydrops fetalis as early as 19 and 22 weeks, associated with intrauterine growth retardation, hyperechogenic kidneys and bones. Amniotic fluid was dark brown and uro- and coproporphyrin I was dramatically increased. Molecular screening of the CEP gene detected heterozygous C73R mutation in both fetuses, the other parental mutation being as yet unknown.

Prenatal diagnosis of fetal tail and postabortum anatomical description.

Fetal ultrasound examination at 13 weeks of gestation demonstrated a homogeneously echogenic protrusion, or tail, 7 mm in length, in the sacral region. At 15 weeks, the ultrasound appearance was consistent with a regression of the tail and by 21 weeks it had completely disappeared. Severe intrauterine growth restriction with reduced uterine blood flow was diagnosed at 21 weeks and intrauterine death occurred at 24 weeks of gestation. Postmortem examination revealed a 4-mm caudal appendage which contained no vertebrae on radiography. The appendage was located under and behind the last sacral vertebra suggesting a true vestigial tail with a delayed process of regression.

Sonographic measurement of the fetal iliac angle cannot be used alone as a marker for trisomy 21.

The fetal iliac wings angle was studied in 255 fetuses before amniocentesis at 16.7 weeks (+/- 1.3), using a sonographic axial view of the fetal pelvis. The measurement could be performed in 208 fetuses (81.6%), of whom 4 had trisomy 21 (T 21). The mean iliac angle was greater in fetuses with T 21 than in normal fetuses (69.8 degrees vs. 88.7 degrees; p = 0.03). This measurement is subject to significant intra- and interexaminer variability (interclass correlation coefficient: 0.65 and 0.23, respectively). When a 90 degrees value is used as a threshold, specificity, sensitivity, positive and negative predictive values are, respectively, 80, 75, 7. 0 and 99.4%. The 20% rate of false-positives rules out the use of this measurement as the sole criterion for the indication of amniocentesis for T 21 antenatal diagnosis.

Dating biometry during the first trimester: accuracy of an every-day practice.

OBJECTIVE: The goal of this study was to determine the accuracy of an every-day practice for assessing gestational age by ultrasound measurement of the greatest embryonic length (GEL). DESIGN: This retrospective study used measurements taken during the first trimester. SUBJECTS: We considered all births in this hospital between 1 January 1992 and 31 December 1994 from pregnancies that began by an in-vitro fertilization procedure (IVF). We examined 143 consecutive files, containing 257 measurements made by 72 different operators. METHODS: The precision of seven embryo growth curves was compared. We calculated for each curve its ability to predict (95% prediction interval) the date the pregnancy began, using these dated pregnancies. RESULT: For GEL measurements between 3 and 80 mm, which includes most of our population, Robinson and Wisser (2) were the most appropriate curves. The 95% prediction interval was 9.5 and 10.2 days respectively. CONCLUSION: Dating pregnancies in every-day practice with GEL is nearly as accurate as prospective studies with only one or two scanners.

Synthesis of glycosaminoglycans by human cervical fibroblasts in culture: effects of prostaglandin E2 and cyclic AMP.

OBJECTIVE: To study the mechanism of action of prostaglandin E2 (PGE2) and its analogue sulprostone leading to production of glycosaminoglycans (GAGs) in the human uterine cervix. STUDY DESIGN: We analysed the effects of PGE2 and its analogue sulprostone upon production of adenosine 3',5'-monophosphate (cAMP), in human cultured fibroblasts. We also studied the effects of PGE2, sulprostone and a cAMP analogue (8-Bromo-cAMP), on the incorporation of [3H]glucosamine into GAGs in human cervical fibroblasts in culture. RESULTS: Following treatment with PGE2 (10(-4)-10(-6) M), we observed a significant increase in the production of cAMP from 96.3 +/- 8.4 pmol/10(6) cells without phosphodiesterase inhibitor 3-isobutyl-methylxanthine (IBMX) to 325 +/- 63 pmol/10(6) cells with 10(-4) M IBMX (Spearman correlation test; P < 0.05). Under the same conditions, the effects of sulprostone (10(-6) M) were limited (from 8.1 +/- 1.5 to 51.3 +/- 14.1 pmol/10(6) cells without and with IBMX, respectively; not significant). Both PGE2 and 8-bromo-cAMP (from 10(-12) to 10(-4) M) increased [3H]glucosamine uptake into GAGs (Spearman correlation test; P < 0.05). Sulprostone (10(-12)-10(-4) M) was unable to reproduce such an effect even after a 24 or 48 h treatment. CONCLUSION: Since firstly, PGE2 acts through EP1, EP2 and EP3 specific receptors, whereas the action of sulprostone is only mediated by EP1 and EP3, and secondly EP2 receptor is coupled with cAMP production, we conclude that cAMP is involved in mediating the action of PGE2 upon GAG synthesis by human cultured cervical fibroblasts.

Treatment of symptomatic polyhydramnios with indomethacin.

Polyhydramnios carries a poor fetal prognosis with an expected neonatal death rate of nearly 30%. Approximately one-fourth of this perinatal mortality is a result of the effects of prematurity. The poor outcome with usual management of polyhydramnios led us to introduce the therapeutic use of prostaglandin synthetase inhibitors so as to decrease amniotic fluid volume and to prevent premature labor. Twenty-two women (20 singleton and two twin pregnancies) were included in a retrospective study from 1983 to 1992. Indomethacin was given at a dose of 3 mg/kg/day. Treatment was started at 28.2 +/- 3.8 weeks of amenorrhea and discontinued after 35 weeks. We observed a significant effect of indomethacin on amniotic fluid volume and avoided severe preterm delivery in all patients. Mean gestational age at birth was 37.5 +/- 1.6 weeks of amenorrhea (range 35.5-39 weeks). We did not observe any maternal or neonatal side effects of indomethacin therapy. However, we reported three neonatal deaths out of 24 infants: two related to undiagnosed fetal anomalies (one Nager syndrome and one cerebral malformation) and one related to umbilical cord entanglement in a monoamniotic twin pregnancy. Since our first report, several open studies supporting our data have been published. However, although indomethacin appears to be effective in the treatment of polyhydramnios, our goal is to analyze efficacy and side effects, so as to define conditions of clinical use.

Insulin-like growth factor-binding proteins in the human fetus: tissue-specific protein secretion, immunologic characterization, and gene expression.

OBJECTIVES: The objectives of this study were to investigate the profile of insulin-like growth factor-binding proteins secreted by human fetal tissues and their immunologic identification and tissue-specific gene expression. STUDY DESIGN: Explants of midgestational fetal tissues from seven fetuses were cultured with and without cycloheximide. Conditioned media were examined for insulin-like growth factor-binding proteins by Western ligand blot analysis, and insulin-like growth factor-binding proteins were identified by immunoprecipitation. Gene expression was analyzed by Northern analysis. RESULTS: Fetal liver and kidney explants secreted insulin-like growth factor-binding protein-1 to insulin-like growth factor-binding protein-4, with insulin-like growth factor-binding protein-1 being the most prominent in liver. Fetal lung secreted insulin-like growth factor-binding protein-2 and insulin-like growth factor-binding protein-4 and lesser amounts of insulin-like growth factor-binding protein-3, whereas white matter explants secreted exclusively insulin-like growth factor-binding protein-2 and insulin-like growth factor-binding protein-4. Cycloheximide inhibited secretion of binding proteins, suggesting de novo synthesis. Northern blot analyses were consistent with the protein studies. CONCLUSION: These data demonstrate that insulin-like growth factor-binding protein secretion by fetal tissues is tissue specific.

Insulin-like growth factor (IGF), IGF binding protein (IGFBP), and IGF receptor gene expression and IGFBP synthesis in human uterine leiomyomata.

Oestradiol is important in the growth of uterine leiomyomata and may act primarily or secondarily through mediators such as growth factors, including the insulin-like growth factors (IGF-I and IGF-II), mitogenic peptides. IGF binding proteins (IGFBPs) modulate IGF actions at their target cells. The objective of this study was to examine the possible steroid dependence of IGF, IGFBP and IGF receptor gene expression and IGFBP synthesis in uterine leiomyomata, using tissues from women cycling normally and made hypo-oestrogenic by a gonadtrophin-releasing hormone agonist (GnRHa). Using a solution hybridization ribonuclease protection assay, anti-sense RNA probes for IGF-I, IGF-II and beta-actin (control) were hybridized with total RNA isolated from leiomyomata exposed in vivo to a range of serum oestradiol (< 40-240 pg/ml) and progesterone (0-10 ng/ml) concentrations. IGF-I gene expression was most abundant in leiomyomata obtained during the late proliferative phase of the cycle and was undetectable in leiomyomata from hypo-oestrogenic patients. IGF-II gene expression was not dependent on endogenous steroid concentrations or cycle stage. IGFBP gene expression was investigated by Northern blotting. The order of relative abundance of IGFBP mRNAs was IGFBP-4 >>> IGFBP-3 >> IGFBP-5 > IGFBP-2 and was not dependent on the in-vivo oestrogen status. Type I and type II IGF receptor gene expression was investigated by polymerase chain reaction using gene-specific primers. Type I and type II IGF receptor mRNAs were detected in leiomyomata and were not dependent on cycle stage or in-vivo oestrogen status. Explant cultures of leiomyomata and myometrium synthesized IGFBP-3 (mol. wt = 38-43 kDa), IGFBP-4, and binding proteins of mol. wt = 34 and 31 kDa. Identification of IGFBP-2 was inconclusive, and IGFBP-1 was not detected. These data support the hypothesis that IGF-I, but not IGF-II, may be a mediator of oestradiol action in the growth of uterine leiomyomata, and that IGFBPs may further modulate, by an autocrine or paracrine mechanism, IGF-I action in this tissue.