Françoise Muller

Fetal Toxic Effects of Angiotensin II Receptor Antagonists: Case Report and Follow-Up after Birth

OBJECTIVE: To report a child born with renal impairment following severe anhydramnios due to maternal exposure to an angiotensin II receptor type 1 (AT1) antagonist, valsartan, and hydrochlorothiazide during the first 28 weeks of pregnancy. CASE SUMMARY: A hypertensive woman treated with valsartan 80 mg/day, hydrochlorothiazide 12.5 mg/day, prazosin 10 mg/day, lysine acetylsalicylate 100 mg/day, and levothyroxine 250 μg/day became pregnant. At 28 weeks gestational age, severe anhydramnios associated with high β2-microglobulin levels in the fetal blood cord was observed. Upon discontinuation of valsartan, fetal renal prognosis improved. In this case, using the Naranjo probability scale, the renal insufficiency of the child was probably related to valsartan. At the age of 2.5 years, the child presented with only mild chronic renal insufficiency. Growth parameters were within the normal range, and there was no evidence of developmental delay. DISCUSSION: Exposure to AT1 antagonists during the second part of pregnancy can lead to abnormalities similar to those observed after exposure to angiotensin-converting enzyme inhibitors, that is, reduced fetal kidney perfusion that may result in oligoamnios and neonatal renal insufficiency. Fourteen previous reports of maternal exposure to AT1 antagonists during this period have been published. In 6 cases, fetal or neonatal death occurred; in 2 cases, pregnancy was terminated because of complete anhydramnios or fetal abnormalities; in 1 case, renal insufficiency persisted at 8 months of age; in 2 cases, kidney function was fairly normal at birth; and in 4 cases, including the one described here, neonatal renal failure improved in the first year of life. CONCLUSIONS: AT1 antagonists should be avoided throughout pregnancy. If these agents are prescribed accidentally to a pregnant woman, monitoring of amniotic fluid volume and β2-microglobulin fetal blood levels after discontinuation of the AT1 antagonist can provide critical data for advising parents on pregnancy and fetal outcome.

Second-trimester Down syndrome maternal serum marker screening: a prospective study of 11 040 twin pregnancies.

To analyze the value of Down syndrome (DS) second‐trimester maternal serum screening in large series of twin pregnancies.

Nonvisualization of the fetal gallbladder by second‐trimester ultrasound scan: strategy of clinical management based on four examples

When the fetal gallbladder is not seen at ultrasound (US) scan, to propose a diagnostic method of differentiating fetuses who are healthy or have minor anomalies from fetuses with severe anomalies requiring intensive management.

Screening for adverse pregnancy outcome at early gestational age

In the past two decades second-trimester maternal serum screening for Down syndrome has been the most common strategy for prenatal diagnosis of chromosomal aneuploidies. More recently, screening for and diagnosis of chromosomal abnormalities have increasingly been performed in the first trimester. With improvements and technological advances in ultrasound, it is now possible to identify many fetal anomalies at 11-13 weeks of gestation. During the same period biochemical markers in maternal serum (PAPP-A and hCGβ) combined with sonographic measurement of nuchal translucency achieve a Down syndrome detection rate of 85% with a 5% false-positive rate. We describe here the potential of first-trimester markers to screen for Down syndrome as well as other adverse outcomes such as fetal loss, pre-eclampsia, intrauterine growth retardation, and preterm delivery. This early consultation may be the opportunity to help counsel patients and to screen for other adverse complications during pregnancy, such as pre-eclampsia, and to manage potential adverse pregnancy outcomes.

Second-trimester maternal serum markers and placenta accreta

Biochimie-Hormonologie, Hôpital Robert Debré, AP-HP, Paris, France Gynécologie-Obstétrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France Biochimie, Université Paris Ile de France Ouest, Versailles, Saint-Quentin, France Gynécologie-Obstétrique, Maternité Port-Royal, Hôpital Cochin, AP-HP, Paris, France French Collaborative Conservative Treatment of Placenta Accreta Study Group Gynécologie-Obstétrique, Hôpital Robert Debré, AP-HP, Paris, France ABA Study Group Gynécologie-Obstétrique, CHU Angers, Angers, France *Correspondence to: Françoise Muller. E-mail: francoise.muller@rdb.aphp.fr

Outcome of prenatally detected bilateral higher urinary tract obstruction or megacystis: sex‐related study on a series of 709 cases

To compare the sex specific outcome of fetuses with prenatally detected urinary tract dilatation, with the exclusion of pyelectasia.

Comprehensive description of CFTR genotypes and ultrasound patterns in 694 cases of fetal bowel anomalies: a revised strategy

Fetal bowel anomalies may reveal cystic fibrosis (CF) and the search for CF transmembrane conductance regulator (CFTR) gene mutations is part of the diagnostic investigations in such pregnancies, according to European recommendations. We report on our 18-year experience to document comprehensive CFTR genotypes and correlations with ultrasound patterns in a series of 694 cases of fetal bowel anomalies. CFTR gene analysis was performed in a multistep process, including search for frequent mutations in the parents and subsequent in-depth search for rare mutations, depending on the context. Ultrasound patterns were correlated with the genotypes. Cases were distinguished according to whether they had been referred directly to our laboratory or after an initial testing in another laboratory. A total of 30 CF fetuses and 8 cases compatible with CFTR-related disorders were identified. CFTR rearrangements were found in 5/30 CF fetuses. 21.2% of fetuses carrying a frequent mutation had a second rare mutation, indicative of CF. The frequency of CF among fetuses with no frequent mutation was 0.43%. Correlation with ultrasound patterns revealed a significant frequency of multiple bowel anomalies in CF fetuses. The results emphasize the need to search for rearrangements in the diagnosis strategy of fetal bowel anomalies. The diagnostic value of ultrasound patterns combining hyperechogenic bowel, loop dilatation and/or non-visualized gallbladder reveals a need to revise current strategies and to offer extensive CFTR gene testing when the triad is diagnosed, even when no frequent mutation is found in the first-step analysis.

Down syndrome maternal serum screening in patients with renal disease

OBJECTIVEnThe objective of the study was to determine the value of maternal serum Down syndrome screening in patients affected by renal disease.nnnSTUDY DESIGNnA study group of 54 pregnant women with renal diseases defined before pregnancy, was compared with a control group of 108 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal serum markers (free beta-human chorionic gonadotropin [hCG], total hCG, alpha-fetoprotein) expressed in multiple of median and maternal renal function markers (creatinine, beta2-microglobulin, alpha1-microglobulin) were assayed.nnnRESULTSnThe percentage of patients in the Down syndrome at-risk group (>1:250) using free beta-hCG was significantly higher (P < .02) in the renal disease group (48%) than in the control group (12%). No significant difference was observed for total hCG (25% vs 15%).nnnCONCLUSIONnDown syndrome screening using free beta-hCG is not applicable in patients with renal disease whatever the maternal serum creatinine and can be used with caution when total hCG is used.

Fetal serum α-1 microglobulin for renal function assessment: comparison with β2-microglobulin and cystatin C.

To compare the prognostic value of fetal serum α1‐microglobulin with that of β2‐microglobulin and cystatin C for postnatal renal function.

Dépistage de la trisomie 21 fœtale par les marqueurs sériques maternels

Resume La trisomie 21 est la plus frequente des anomalies chromosomiques. Pendant de nombreuses annees seuls l’âge maternel et la presence de malformations fœtales decelables a l’echographie ont ete pris en compte comme facteur de risque. Par la suite, des variations de concentrations sanguines de proteines (augmentation de l’hormone gonadochorionique (hCG) et diminution de l’alpha-fœtoproteine (AFP)) ont ete mises en evidence chez les femmes attendant un fœtus trisomique 21. Le dosage des marqueurs seriques maternels a ete alors propose a toutes les femmes enceintes et permet de definir un risque individuel de trisomie 21 fœtale. Un calcul de risque de trisomie 21 est realise a l’aide d’un logiciel adapte, il prend en compte l’âge maternel, les concentrations seriques d’hCG et d’AFP exprimees en multiples de la mediane et differentes donnees maternelles (poids, tabagisme). En France, cette activite est reglementee (arrete du 27 janvier 1997) et actuellement 75 laboratoires ont recu un agrement pour ce depistage. Il permet de depister et de diagnostiquer 73 % des cas de trisomie 21 fœtale au prix de 7 % d’amniocenteses induites. Actuellement, l’objectif est de reduire le nombre d’amniocenteses en realisant un calcul de risque combinant des donnees echographiques (mesure de la clarte nucale) et biochimiques (marqueurs du 1 er trimestre comme la pregnancy associated plasma protein A et la sous-unite libre de l’hCG ou ceux du 2 e trimestre).