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JAMA Dec 2023Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial... (Clinical Trial)
Clinical Trial
IMPORTANCE
Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival.
OBJECTIVE
To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia.
DESIGN, SETTING, AND PARTICIPANTS
Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies.
EXPOSURE
Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age.
MAIN OUTCOMES AND MEASURES
The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement.
RESULTS
The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks).
CONCLUSIONS AND RELEVANCE
Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03101891.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Fetal Therapies; Gestational Age; Kidney; Kidney Diseases; Prospective Studies; Infusions, Parenteral; Oligohydramnios; Fetal Diseases; Lung Diseases; Isotonic Solutions; Ultrasonography, Interventional; Pregnancy Outcome; Treatment Outcome; Premature Birth
PubMed: 38051327
DOI: 10.1001/jama.2023.21153 -
Annals of Medicine Dec 2023To evaluate the clinical utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in foetuses with oligohydramnios.
OBJECTIVES
To evaluate the clinical utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in foetuses with oligohydramnios.
METHODS
In this retrospective study, 126 fetuses with oligohydramnios at our centre from 2018 to 2021 were reviewed. The results of CMA and WES were analysed.
RESULTS
One hundred and twenty-four cases underwent CMA and 32 cases underwent WES. The detection rate of pathogenic/likely pathogenic (P/LP) copy number variant (CNV) by CMA was 1.6% (2/124). WES revealed P/LP variants in 21.8% (7/32) of the foetuses. Six (85.7%, 6/7) foetuses showed an autosomal recessive inheritance pattern. Three (42.9%, 3/7) variants were involved in the renin-angiotensin-aldosterone system (RAAS), which are the known genetic causes of autosomal recessive renal tubular dysgenesis (ARRTD).
CONCLUSION
CMA has low diagnostic utility for oligohydramnios, while WES offers obvious advantages in improving the detection rate. WES should be recommended for fetuses with oligohydramnios.
Topics: Pregnancy; Female; Humans; Retrospective Studies; Exome Sequencing; Oligohydramnios; Microarray Analysis; Fetus; Prenatal Diagnosis
PubMed: 37243546
DOI: 10.1080/07853890.2023.2215539 -
Journal of Family & Reproductive Health Dec 2023The outcomes and management of low amniotic fluid index (AFI) in pregnancy are controversial. The purpose of this study was to determine the relationship between low AFI...
OBJECTIVE
The outcomes and management of low amniotic fluid index (AFI) in pregnancy are controversial. The purpose of this study was to determine the relationship between low AFI and perinatal outcomes.
MATERIALS AND METHODS
This prospective study was conducted on 420 uncomplicated singleton pregnant women with a gestational age of over 28 weeks who referred to Al-Zahra Hospital in Rasht (Iran) for routine perinatal care. Pregnant women were divided into 3 groups of 140 patients based on the AFI and were followed up until delivery. Three groups included normal (8
oligohydramnios (AFI≤5cm) AFI. RESULTS
The three adverse outcomes of respiratory distress, hospitalization in NICU, and length of hospitalization were statistically significantly different between the two groups with normal and borderline AFI and in the borderline group was more than the normal group. Adverse outcomes including; low birth weight (LBW), small for gestational age (SGA), respiratory distress, 1- min APGAR scores<7, hospitalization in NICU and its duration were statistically significantly different between the two groups with normal AFI and oligohydramnios, and it was more in the oligohydramnios group than the normal group. The three adverse outcomes of LBW, SGA and1- min APGAR scores<7 in the two borderline and oligohydramnios groups had statistically significant differences and were more in the oligohydramnios group than the borderline group.
CONCLUSION
Consideration to the AFI in perinatal care to predict adverse perinatal outcomes and perform necessary interventions to improve these outcomes is necessary.
PubMed: 38807617
DOI: 10.18502/jfrh.v17i4.14591 -
JAMA Network Open Oct 2023Targeted therapies directed against ERBB2 are the cornerstone of medical treatment for ERBB2-positive breast cancers but are contraindicated during pregnancy.
IMPORTANCE
Targeted therapies directed against ERBB2 are the cornerstone of medical treatment for ERBB2-positive breast cancers but are contraindicated during pregnancy.
OBJECTIVES
To describe the association of exposure to anti-ERBB2 agents during pregnancy with pregnancy and fetal or newborn outcomes, and to compare the risk and types of adverse outcomes reported more frequently in this context than after exposure to other anticancer agents.
DESIGN, SETTING, AND PARTICIPANTS
For this case-control study, All reports with a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. All reports with a pregnancy, an antineoplastic treatment during pregnancy, and a cancer were retained. Reports with anticancer agents prescribed for nononcologic purposes were not included.
EXPOSURE
The exposure group was defined as reports that mention anti-ERBB2 agents compared with exposure to other anticancer agents.
MAIN OUTCOME AND MEASURES
The main outcome was the reporting odds ratio (ROR) for maternofetal complications in the group exposed to anti-ERBB2 agents compared with other anticancer agents, as determined using a disproportionality analysis.
RESULTS
A total of 3558 reports (anti-ERBB2 agents, 328; other anticancer agents, 3230) were included in the analysis. In the group exposed to anti-ERBB2 agents, most reports were from the US (159 [48.5%]), the mean (SD) age of participants was 30.8 (10.4) years, and 209 patients (97.7%) were treated for breast cancers. The molecules most frequently involved in cases with anti-ERBB2 agents were trastuzumab (n = 302), pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18). The outcomes overreported in these cases included oligohydramnios (ROR, 17.68 [95% CI, 12.26-25.52]; P < .001), congenital respiratory tract disorders (ROR, 9.98 [95% CI, 2.88-34.67]; P < .001), and neonatal kidney failure (ROR, 9.15 [95% CI, 4.62-18.12]; P < .001). Sensitivity and multivariable analyses found similar results. Toxic effects were also significantly overreported for trastuzumab-emtansine (cardiovascular malformation: ROR, 4.46 [95% CI, 1.02-19.52]) and lapatinib (intrauterine growth restriction: ROR, 7.68 [95% CI, 3.01-19.59]).
CONCLUSIONS AND RELEVANCE
In this case-control study of 328 individuals exposed to anti-ERBB2 agents during pregnancy, exposure was associated with a severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Adult; Lapatinib; Case-Control Studies; Trastuzumab; Ado-Trastuzumab Emtansine; Breast Neoplasms; Antineoplastic Agents; Receptor, ErbB-2
PubMed: 37883083
DOI: 10.1001/jamanetworkopen.2023.39934