[Antenatal care for fetuses with congenital diaphragmatic hernia]. / Prise en charge anténatale des fœtus porteurs d'une hernie de coupole diaphragmatique.

Congenital diaphragmatic hernia (CDH) can be diagnosed prenatally and its severity assessed by fetal imaging. The prognosis of a fetus with CDH is based on whether or not the hernia is isolated, the measurement of lung volume on ultrasound and MRI, and the position of the liver. The birth of a child with CDH should take place in a center adapted to the care of such children, and in accordance with the recommendations defined by the French National Diagnosis and Care Protocol. It has recently been demonstrated that for moderate and severe forms of CDH, tracheal occlusion using a balloon placed in utero by fetoscopy (FETO) increases survival until discharge from the neonatal unit, but at the cost of an increased risk of prematurity. At the same time, advances in neonatal resuscitation and the standardization of follow-up of these children within the framework of the "Centre de référence maladies rares: hernie de coupole diaphragmatique" have improved the prognosis of these children and young adults.

Impact of simulation-based prenatal invasive procedure training on professional practice, a preliminary study.

INTRODUCTION: Amniocentesis and chorionic villus sampling remain the cornerstone of prenatal diagnosis. These procedures are associated with a risk of miscarriage estimated at approximately 0.5 %. Our team has developed a training model for performing simulation-based prenatal invasive procedures. Several simulation sessions are offered each year to obstetricians-gynecologists involved in fetal medicine in France and abroad. This simulation-based learning has already been conclusively evaluated according to levels I and II of the Kirkpatrick model. Here, we carried out a preliminary study according to level III: does participation in training in prenatal invasive procedures through simulation have an influence on professional practice? METHODS: An anonymous online survey was sent to 82 obstetricians-gynecologists who participated in the training in prenatal invasive procedures at the Antoine Béclère maternity hospital between January 1st, 2014 and December 31, 2018. This questionnaire, entitled "Evaluation of the professional impact of training in invasive procedures through simulation", included 20 quantitative and qualitative items. RESULTS: 48 (59 %) obstetricians-gynecologists responded to the questionnaire. 98 % of the participants considered that participation in the training had a significant impact on their professional practice. Half considered this impact to be major. 60 % of the former participants are now attached to a Multidisciplinary Center for Prenatal Diagnosis. CONCLUSION: Participation in training is considered by former participants to have a significant impact on their professional practice. In order to finalize the evaluation of this learning, a study of the benefits for patients and their pregnancy should be discussed.

De novo mutations of SCN1A are responsible for arthrogryposis broadening the SCN1A-related phenotypes.

BACKGROUND: Arthrogryposis multiplex congenita (AMC) is the direct consequence of reduced fetal movements. AMC includes a large spectrum of diseases which result from variants in genes encoding components required for the formation or the function of the neuromuscular system. AMC may also result from central nervous involvement. SCN1A encodes Nav1.1, a critical component of voltage-dependent sodium channels which underlie action potential generation and propagation. Variants of SCN1A are known to be responsible for Dravet syndrome, a severe early-onset epileptic encephalopathy. We report pathogenic heterozygous missense de novo variants in SCN1A in three unrelated individuals with AMC. METHODS: Whole-exome sequencing was performed from DNA of the index case of AMC families. Heterozygous missense variants in SCN1A (p.Leu893Phe, p.Ala989Thr, p.Ile236Thr) were identified in three patients. Sanger sequencing confirmed the variants and showed that they occurred de novo. RESULTS: AMC was diagnosed from the second trimester of pregnancy in the three patients. One of them developed drug-resistant epileptic seizures from birth. We showed that SCN1A is expressed in both brain and spinal cord but not in skeletal muscle during human development. The lack of motor denervation as established by electromyographic studies or pathological examination of the spinal cord or skeletal muscle in the affected individuals suggests that AMC is caused by brain involvement. CONCLUSION: We show for the first time that SCN1A variants are responsible for early-onset motor defect leading to AMC indicating a critical role of SCN1A in prenatal motor development and broadening the phenotypic spectrum of variants in SCN1A.

Prenatal exome sequencing in 65 fetuses with abnormality of the corpus callosum: contribution to further diagnostic delineation.

PURPOSE: Abnormality of the corpus callosum (AbnCC) is etiologically a heterogeneous condition and the prognosis in prenatally diagnosed cases is difficult to predict. The purpose of our research was to establish the diagnostic yield using chromosomal microarray (CMA) and exome sequencing (ES) in cases with prenatally diagnosed isolated (iAbnCC) and nonisolated AbnCC (niAbnCC). METHODS: CMA and prenatal trio ES (pES) were done on 65 fetuses with iAbnCC and niAbnCC. Only pathogenic gene variants known to be associated with AbnCC and/or intellectual disability were considered. RESULTS: pES results were available within a median of 21.5 days (9-53 days). A pathogenic single-nucleotide variant (SNV) was identified in 12 cases (18%) and a pathogenic CNV was identified in 3 cases (4.5%). Thus, the genetic etiology was determined in 23% of cases. In all diagnosed cases, the results provided sufficient information regarding the neurodevelopmental prognosis and helped the parents to make an informed decision regarding the outcome of the pregnancy. CONCLUSION: Our results show the significant diagnostic and prognostic contribution of CMA and pES in cases with prenatally diagnosed AbnCC. Further prospective cohort studies with long-term follow-up of the born children will be needed to provide accurate prenatal counseling after a negative pES result.

Case report on early treatment with valaciclovir after maternal primary cytomegalovirus infection.

BACKGROUND: Cytomegalovirus (CMV) is the main cause of congenital viral infections. Current guidelines do not include any recommendation about antenatal treatment. Most studies that evaluate the efficacy of valaciclovir aim to treat infected symptomatic fetus but the benefit of anti-CMV therapy remains unclear. CASE PRESENTATION: We report the case of cytomegalovirus seroconversion during the second trimester of pregnancy. Early treatment with valaciclovir was introduced, associated with a close monitoring of maternal CMV viremia. The virus was no longer detected in maternal blood soon after the beginning of antiviral therapy. Valaciclovir was stopped at 24 + 5 WG after negative prenatal diagnosis but CMV viremia was still monitored in maternal blood until the end of pregnancy. CONCLUSION: The neonate was not infected and remained asymptomatic. It suggests that early treatment with valaciclovir 8 g per day could be effective in quickly reducing maternal viral load and lowering the risk of vertical CMV transmission.

Reproducibility of fetal lung-to-head ratio in left diaphragmatic hernia across the North American Fetal Therapy Network (NAFTNet).

OBJECTIVE: To determine the antenatal sonographic lung area measurement method in left congenital diaphragmatic hernia (CDH) with the highest interrater agreement among North American Fetal Therapy Network (NAFTNet) centers within and outside the fetoscopic tracheal occlusion (FETO) consortium and in comparison with a European "expert" reviewer (ER). METHODS: Nineteen members from nine FETO consortium centers and 29 reviewers from 17 non-FETO centers reviewed ultrasound clips of the chest from 13 fetuses with isolated left CDH and were asked to select a static plane for lung area measurement using anteroposterior (AP), longest, and trace methods. Interrater agreement in lung area measurements was determined using intraclass correlation coefficient (ICC). Bland-Altman analysis was used to evaluate mean difference (bias) between NAFTNet reviewers and ER. RESULTS: Among FETO centers, agreement was highest using trace (ICC 0.94; 95% CI, 0.83-0.98), followed by longest (ICC 0.89; 95% CI, 0.75-0.97) and lowest for A-P (ICC 0.83; 95% CI, 0.67-0.94). Similar trends were noted in non-FETO centers. When compared with ER, bias was lowest for trace: 14 ± 38 mm2 and 19 ± 36 mm2 for FETO and non-FETO centers, respectively. CONCLUSION: The trace method demonstrated the highest interrater agreement and lowest bias for lung area estimation in left CDH across NAFTNet.

Proposal for standardized prenatal ultrasound assessment of the fetus with congenital diaphragmatic hernia by the European reference network on rare inherited and congenital anomalies (ERNICA).

Congenital diaphragmatic hernia is a rare disease associated with high mortality and morbidity. Antenatal ultrasound screening identifies more than 70% of cases, providing the opportunity for in utero referral to a tertiary care center for expert assessment and perinatal management. Additional genetic and morphologic assessment may be used to rule out associated anomalies. In isolated cases, the outcome may be predicted prenatally by medical imaging. The combination of lung size and liver herniation is a widely accepted method to stratify fetuses into groups with an increasing degree of pulmonary hypoplasia and corresponding mortality rates. Ultrasound measurement of the observed to expected lung-to-head ratio (o/e LHR) is most widely used. The o/e LHR is an independent predictor of survival and short-term morbidity. Finally, evaluation of stomach position has recently been introduced as an indirect method to estimate severity of the disease in left-sided defects, as it has been shown to correlate with the proportion of intrathoracic liver. Herein, we propose a protocol for the standardized ultrasound assessment of fetuses with isolated CDH and individualized prediction of neonatal outcome.

Congenital diaphragmatic hernia has a better prognosis when associated with a hernia sac.

OBJECTIVE: To evaluate neonatal mortality and morbidity up to 6 months in neonates with congenital diaphragmatic hernia (CDH) with or without a hernia sac. METHODS: Seventy-two cases of isolated CDH were included in a retrospective single-center study between January 2010 and December 2016. Hernia sac was defined at the time of surgery or at postmortem examination if the neonate died before surgery. RESULTS: Seventeen newborns (23.6%) had a hernia sac. Survival at 6 months was significantly greater for isolated CDH with a hernia sac: 100% versus 63.6% (P = .003). High-frequency oscillatory ventilation was used significantly more in the no hernia sac group (P = .04). At surgery, the need for patch repair was significantly lower in the hernia sac group: 12% versus 50% (P = .005). The prenatal observed/expected lung-to-head ratio was significantly higher in the hernia sac group than in the no hernia sac group: 49.7% versus 38.6% (P < .05). CONCLUSION: The presence of a hernia sac in CDH is associated with better outcome, especially survival at 6 months. If the presence of a hernia sac is recognized as a particular entity, which carries a good prognosis, it is necessary to be able to diagnose it prenatally, especially in the era of prenatal fetal surgery.

Prenatal Diagnosis of a 2.5 Mb De Novo 17q24.1q24.2 Deletion Encompassing KPNA2 and PSMD12 Genes in a Fetus with Craniofacial Dysmorphism, Equinovarus Feet, and Syndactyly.

Interstitial 17q24.1 or 17q24.2 deletions were reported after conventional cytogenetic analysis or chromosomal microarray analysis in patients presenting intellectual disability, facial dysmorphism, and/or malformations. We report on a fetus with craniofacial dysmorphism, talipes equinovarus, and syndactyly associated with a de novo 2.5 Mb 17q24.1q24.2 deletion. Among the deleted genes, KPNA2 and PSMD12 are discussed for the correlation with the fetal phenotype. This is the first case of prenatal diagnosis of 17q24.1q24.2 deletion.

Teaching invasive prenatal procedures: effectiveness of two simple simulators in training.

BACKGROUND: Chorionic villus sampling (CVS) and amniocentesis are the major tools of invasive prenatal diagnosis. We studied the effectiveness of two simulators in training in invasive procedures. METHODS: Two affordable and simple simulators were developed, modelling the maternal abdomen and the different tissue layers crossed by the needle. The trainees were evaluated before and after practical and theoretical training. A score evaluating five criteria for technical quality in performing a procedure safely was established. Initial score of 9 or 10 was excluded. The primary endpoint was improvement defined as the change between pre-test and post-test, expressed as a percentage of the pre-test. RESULTS: A total of 54 residents and 63 specialists in obstetrics and gynaecology participated. Residents improved their scores in the practice of amniocentesis (80% [43-167]) and CVS (100% [29-150]), as well as specialists (100% [25-233] and 67% [33-122]). Specialists who earlier performed one CVS or more than five amniocentesis procedures had a lower increase during training than those who had performed fewer than five procedures (p < 0.01). Being inexperienced in CVS was associated with greater improvement (27% vs 56%, p = 0.003). CONCLUSION: A simple simulator improves the ability of physicians to perform invasive procedures in particular when initial experience is low. © 2016 John Wiley & Sons, Ltd.

Sonographic Evaluation of Fetal Conus Medullaris and Filum Terminale.

BACKGROUND: Sonographic evaluation of the fetal conus medullaris (CM) level is not reproducible. The objectives of this study were to determine the normal position of the fetal CM during pregnancy as well as the normal intradural filum terminale (FT) length and to evaluate their use in detecting tethered cord. METHODS: This is a prospective evaluation of normal singleton pregnancies examined by sonography from 17 weeks of gestation to term. Each sonographer had to identify the top of the first sacral vertebra (S1) to measure the distance between it and the conus extremity (CM-S1 distance). The intradural FT distance was measured with 5- to 8-MHz probes. RESULTS: 194 consecutive pregnant women were included. The CM and intradural FT were demonstrated clearly in 164 (84%) cases. The mean CM-S1 distance was 20.6 mm (range 0.5-42). The mean intradural FT distance was 27.9 mm (range 6.6-49.3). Linear regression analysis showed a significant association between both those distances and gestational age (p < 0.05). In cases of tethered cord, the mean CM-S1 distance and the mean intradural FT distance were both below the 5th percentile. CONCLUSION: Prenatal evaluation of the CM and the intradural FT is feasible and reproducible and seems useful in detecting tethered cord.

Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations.

We report paternally inherited duplication of 1q12q21.2 of 5.8 Mb associated with maternally inherited deletion of 16p11.2 of 545 Kb, this latter first identified in a fetus exhibiting an absent nasal bone detected during pregnancy. During the neonatal period, the young boy presented developmental delay, epilepsy, congenital anomalies and overweight. The clinical features of the proband with two rearrangements were more severe than in either of the parents carrying only one or the other mutation. Thus our data support a two-hit model in which the concomitant presence of these two copy-number variations exacerbates the neurodevelopmental phenotype.

A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium.

Joubert syndrome (JS) is characterized by a distinctive cerebellar structural defect, namely the << molar tooth sign >>. JS is genetically heterogeneous, involving 20 genes identified to date, which are all required for cilia biogenesis and/or function. In a consanguineous family with JS associated with optic nerve coloboma, kidney hypoplasia, and polydactyly, combined exome sequencing and mapping identified a homozygous splice-site mutation in PDE6D, encoding a prenyl-binding protein. We found that pde6d depletion in zebrafish leads to renal and retinal developmental anomalies and wild-type but not mutant PDE6D is able to rescue this phenotype. Proteomic analysis identified INPP5E, whose mutations also lead to JS or mental retardation, obesity, congenital retinal dystrophy, and micropenis syndromes, as novel prenyl-dependent cargo of PDE6D. Mutant PDE6D shows reduced binding to INPP5E, which fails to localize to primary cilia in patient fibroblasts and tissues. Furthermore, mutant PDE6D is unable to bind to GTP-bound ARL3, which acts as a cargo-release factor for PDE6D-bound INPP5E. Altogether, these results indicate that PDE6D is required for INPP5E ciliary targeting and suggest a broader role for PDE6D in targeting other prenylated proteins to the cilia. This study identifies PDE6D as a novel JS disease gene and provides the first evidence of prenyl-binding-dependent trafficking in ciliopathies.

Prenatal diagnosis of bilateral ectrodactyly and radial agenesis associated with trisomy 10 mosaicism.

Ectrodactyly or split hand and foot malformations (SHFMs) are rare malformations of the limbs, characterized by median clefts of the hands and feet, syndactyly, and aplasia and/or hypoplasia of the phalanges. They represent a clinically and genetically heterogeneous disorder, with both sporadic and familial cases. Most of the genomic rearrangements identified to date in some forms of SHFM are autosomal dominant traits, involving various chromosome regions. Bilateral radial ray defects comprise also a large heterogenous group of disorders, including trisomy 18, Fanconi anemia, and thrombocytopenia-absent-radius syndrome, not commonly associated with ectrodactyly. The present paper describes a case of ectrodactyly associated with bilateral radial ray defects, diagnosed in the first trimester of pregnancy, in a fetus affected by trisomy 10. Only four cases of sporadic and isolated ectrodactyly, diagnosed by ultrasonography between 14 and 22 weeks' gestation, have been reported. To our knowledge, the present case is the first report of mosaic trisomy 10 associated with SHFM and radial aplasia. Trisomy 10 is a rare lethal chromosomal abnormality, most frequently found in abortion products. Only six liveborn mosaic trisomy 10 infants, with severe malformations, dead in early infancy, have been reported. A severe clinical syndrome can be defined, comprising ear abnormalities, cleft lip/palate, malformations of eyes, heart, and kidneys, and deformity of hands and feet and most often associated with death neonatally or in early infancy.

Modulation of free corticotrophin-releasing hormone, adrenal and placental steroid hormone levels induced by mifepristone during pregnancy.

UNLABELLED: Mifepristone is a progesterone receptor antagonist widely used in obstetrics. The aim of the study was to focus on free corticotrophin-releasing hormone (CRH) and also describe modulation of adrenal and placental steroid hormone concentrations induced by mifepristone. METHODS: Twenty-six women were enrolled in the study. They received mifepristone for termination of pregnancy. Maternal blood samples were retrieved before administration of mifepristone (600 mg) and 48 h after, just before induction of labor. Bound and free CRH levels were determined in maternal blood concomitantly with cortisol, estriol, progesterone and SDHEA levels. Also paired fetal cord blood samples were collected. RESULTS: Maternal plasmatic CRH level did not change after mifepristone absorption but free CRH increased significantly (0.500 ± 0.326 vs. 0.388 ± 0.303 ng/ml, p = 0.040). A significant decrease of progesterone was observed (83.6 ± 49.3 vs. 95.6 ± 54.9 ng/ml, p = 0.001) with a lower progesterone/estriol ratio (26.9 ± 15.7 vs. 40.7 ± 31.1, p = 0.004). There was a strong association between maternal and fetal free CRH (r² = 0.675, p = 0.001), cortisol (r² = 0.570, p = 0.019), and positive but modest correlation for progesterone (r² = 0.341, p = 0.046) and estriol (r² = 0.379, p = 0.025) levels. CONCLUSION: Mifepristone has an effect on free CRH level and changes the estriol-progesterone balance.

Quantitative analysis of renal vascularization in fetuses with urinary tract obstruction by three-dimensional power-Doppler.

OBJECTIVE: To evaluate the applicability of 3-dimensional evaluation of renal vascularization for predicting postnatal renal function in fetuses with suspected urinary obstruction. STUDY DESIGN: Fetuses were evaluated by 3-dimensional power-Doppler histogram, and vascular indices were estimated. Depth between the probe and the renal cortex was also evaluated. Postnatal follow-up was obtained in all cases and the main outcome was renal impairment. RESULTS: Twenty-three fetuses with urinary dilatation (cases) and 73 with normal renal morphology (controls) were included in the current study. Five (21.7%) cases developed renal impairment. Vascularization index and vascularization and flow index were significantly lower in fetuses that developed renal impairment compared with those with normal renal function (P = .009 and P = .036, respectively). The 3 vascular indexes correlated with depth. Percentage of depth-corrected vascularization index and vascularization flow index were lower in fetuses developing postnatal renal failure. CONCLUSION: Fetal renal vascularity (vascularization index and vascularization and flow index) was significantly lower in fetuses that developed renal impairment.

Combining keratinocyte growth factor transfection into the airways and tracheal occlusion in a fetal sheep model of congenital diaphragmatic hernia.

BACKGROUND: In utero tracheal occlusion (TO) has been developed to improve the lung hypoplasia associated with congenital diaphragmatic hernia (CDH). However, although TO stimulates fetal lung growth, it results in a decrease of alveolar type II cells (ATII) and surfactant production. Because keratinocyte growth factor (KGF) is a potent stimulus of ATII proliferation and maturation, we evaluated, in a fetal lamb model of CDH, a gene therapy strategy combining TO and ovine KGF transfection into the fetal airways using bisguanidinium-tren-cholesterol/dioleoyl-phosphatidylethanolamine (BGTC/DOPE) cationic liposomes. METHODS: Three groups of sheep fetuses with CDH and a group of normal fetuses were studied. The fetuses of the three groups with CDH (KGF, Medium and Hernia groups) underwent surgery at 85 days of gestation to create a diaphragmatic hernia. The KGF and medium group fetuses underwent a second surgery step at day 125 to perform TO associated with injection of the KGF transfection mixture (KGF group) or control medium (Medium group), whereas the fetuses of the Hernia group were left untreated. Normal fetuses were used as a control (Normal group). All fetuses were euthanized at 132 days of gestation and various analytical studies [lung weight, radial alveolar count (RAC), KGF and surfactant protein B (SPB) expression, number of ATII cells] were performed to assess the efficiency of KGF transfection and its effects on fetal lung development. RESULTS: TO was associated with lung hyperplasia and increased RAC in the Medium and KGF groups versus the Hernia group. Expression of KGF was increased in the KGF group compared to all other groups and was associated with an increased synthesis of SPB by alveolar cells and an ectopic synthesis of SPB by bronchiolar cells compared to TO treatment alone. CONCLUSIONS: Thus, BGTC/DOPE liposomes can mediate efficient KGF transfection into the airways in a fetal sheep model of CDH. Furthermore, combining KGF transfection and TO resulted not only (as did TO alone) in the correction of the CDH-associated lung hypoplasia and decreased RAC, but also in increased SPB synthesis, suggesting a better maturation of the re-growing lung (compared to TO alone). Additional studies are required to further explore the therapeutic potential of such a combined strategy; in particular, studies evaluating the lung function of in utero-treated CDH lamb newborns.

Efficacy of selective arterial embolisation for the treatment of life-threatening post-partum haemorrhage in a large population.

BACKGROUND: The objective of this study was to assess efficacy and determine the optimal indication of selective arterial embolisation (SAE) in patients with life-threatening post-partum haemorrhage (PPH). METHODOLOGY/PRINCIPAL FINDINGS: One hundred and two patients with PPH underwent SAE and were included from January 1998 to January 2002 in our university care center. Embolisation was considered effective when no other surgical procedure was required. Univariate and multivariate statistical analysis were performed. SAE was effective for 73 patients (71.5%), while 29 required surgical procedures. SAE was effective in 88.6% of women with uterine atony that was associated with positive outcome (OR 4.13, 1.35-12.60), whereas caesarean deliveries (OR 0.16, 0.04-0.5) and haemodynamic shock (OR 0.21, 0.07-0.60) were associated with high failure rates, 47.6% and 39.1%, respectively. CONCLUSIONS/SIGNIFICANCE: Success rate for SAE observed in a large population is lower than previously reported. It is most likely to succeed for uterine atony but not recommended in case of haemodynamic shock or after caesarean section.

Prenatal cortical hyperostosis with COL1A1 gene mutation.

Infantile cortical hyperostosis (Caffey disease) is benign and self-limiting when it presents near or after birth but it is usually lethal when it presents earlier. We present the clinical, ultrasonic, radiographic, and pathologic findings in an instructive case of early onset prenatal cortical hyperostosis. The pregnancy of a 21-year-old woman was medically terminated at 30 weeks of gestation after a diagnosis of severe osteogenesis imperfecta. Prenatal ultrasounds showed short long bones. Postmortem radiographs showed hyperostosis in long bones, ribs and mandible. The affected skeleton showed marked bony sclerosis and ballooning of the diaphyses of the long bones with periosteal sclerosis. A complete autopsy showed characteristic histologic findings of infantile cortical hyperostosis in affected bones. A missense mutation (3040C --> T) in exon 41 the gene encoding the alpha 1 chain of type I collagen was found in fetus pulmonary tissue. Neither the severe form nor the mild form of prenatal cortical hyperostosis were thought to be related to collagen I mutations. Our study indicates that a heterozygous 3040C --> T mutation can also be found in lethal prenatal cortical hyperostosis.

Idiopathic hemoptysis in pregnant women: a distinct entity?

In pregnant women, the reported cases of hemoptysis were most often mild and had an identified cause. Between November 2003 and January 2006, three pregnant women at 16-20 weeks gestation were admitted to our respiratory intensive care unit for massive hemoptysis. One of the women had experienced mild hemoptysis, considered as idiopathic, during her first pregnancy, with no recurrence until her second pregnancy. In all three cases, hemoptysis was massive. CT scan after iodine injection did not reveal any cause. Opacification of the bronchial artery showed hyperemia from abnormally dilated and tortuous bronchial arteries. Bronchial artery embolization (BAE) was performed in all three patients, successfully in two. Intravenous vasopressin was used as second-line treatment for recurrent bleeding after BAE in one patient. The women carried the pregnancy to term with delivery of healthy infants. Further complete investigation after the births did not identify any possible local (pulmonary) or general cause of bleeding in these three patients. Although these cases could be considered idiopathic, the close association with duration of pregnancy suggests the hemoptysis may be related to hormonal changes.