Implication of chromosomal microarray analysis prior to in-utero repair of fetal open neural tube defect.

OBJECTIVE: In-utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in-utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in-utero ONTD repair. METHODS: This was a retrospective cohort study of pregnancies complicated by ONTD that underwent laparotomy-assisted fetoscopic repair or open-hysterotomy fetal surgery at a single tertiary center between September 2011 and July 2021. All patients met the MOMS eligibility criteria and had a normal karyotype. In a subset of the pregnancies (n = 77), CMA testing was also conducted. We reviewed the CMA results and divided the cohort into two groups according to whether clinically reportable copy-number variants (CNV) were detected (reportable-CNV group) or not (normal-CMA group). Surgical characteristics, complications, and maternal and early neonatal outcomes were compared between the two groups. The primary outcomes were fetal or neonatal death, hydrocephalus, motor function at 12 months of age and walking status at 30 months of age. Standard parametric and non-parametric statistical tests were employed as appropriate. RESULTS: During the study period, 146 fetuses with ONTD were eligible for and underwent in-utero repair. CMA results were available for 77 (52.7%) patients. Of those, 65 (84%) had a normal CMA and 12 (16%) had a reportable CNV, two of which were classified as pathogenic. The first case with a pathogenic CNV was diagnosed with a 749-kb central 22q11.21 deletion spanning low-copy-repeat regions B-D of chromosome 22; the second case was diagnosed with a 1.3-Mb interstitial deletion at 1q21.1q21.2. Maternal demographics, clinical characteristics, operative data and postoperative complications were similar between those with normal CMA results and those with reportable CNVs. There were no significant differences in gestational age at delivery or any obstetric and early neonatal outcome between the study groups. Motor function at birth and at 12 months of age, and walking status at 30 months of age, were similar between the two groups. CONCLUSIONS: Standard diagnostic testing with CMA should be offered when an ONTD is detected prenatally, as this approach has implications for counseling regarding prognosis and recurrence risk. Our results indicate that the presence of a clinically reportable CNV should not a priori affect eligibility for in-utero repair, as overall pregnancy outcome is similar in these cases to that of cases with normal CMA. Nevertheless, significant CMA results will require a case-by-case multidisciplinary discussion to evaluate eligibility. To generalize the conclusion of this single-center series, a larger, multicenter long-term study should be considered. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal heart rate mirrors maternal temperature during posterior fossa craniotomy: a case report.

While it is well known that maternal temperature affects fetal heart rate, the exact relationship is not well described. The circumstances accompanying most cases of maternal hypothermia and rewarming (e.g. a drowning event) have precluded a precise quantitative description of this relationship. We describe hypothermia and controlled rewarming during resection of a maternal brain stem tumor in the early third trimester. Continuous electronic fetal heart rate and core temperature monitoring demonstrated a near linear relationship during the development of hypothermia and rewarming. Recognition of the close relationship between maternal temperature and fetal heart rate can help safeguard maternal and fetal health, and prevent unnecessary delivery during non-obstetric surgery in pregnancy.

Molecular phylogenetic evidence for a reversible morphogenetic switch controlling the gross morphology of two common genera of green seaweeds, Ulva and Enteromorpha.

Ulva and Enteromorpha are two of the most common, ubiquitous, and environmentally important genera of green seaweeds. They are widely regarded as easily distinguishable because of their dramatically different morphologies: Ulva species are flat, lettucelike blades two cell layers thick, and Enteromorpha species form hollow liquid- or gas-filled tubes one cell thick, which may also be highly branched. We present molecular phylogenetic analyses of nuclear ribosomal RNA ITS sequences from 39 samples representing 21 purported species within these two genera. The results clearly indicate that the two genera are not respectively monophyletic and that the characteristic Ulva and Enteromorpha morphologies have arisen independently several times throughout the evolutionary diversification of the group. The analyses demonstrate that this radical change in gross morphology can also happen within clades exhibiting sequence divergence typical of conspecific assemblages of this group. We suggest that this morphological flexibility is the result of some form of developmental switch that results in either blades or tubes, but that this putative switch must be activated relatively infrequently, since there is evidence that some lineages have retained their form for significant periods. This discovery suggests a possible new model system for study of the molecular mechanisms involved in the interplay between environmental stimuli and plant development.

Tonsillectomy--some like it hot.

Methods of tonsillectomy using electrocautery for dissection and hemostasis are gaining popularity. A prospective, controlled, randomized, single blind study was designed to compare this method to tonsillectomy performed by scissor dissection with suture hemostasis. In general, tonsillectomy by electrocoagulation was found to reduce operative time and blood loss, and to increase postoperative pain and prolong healing. Overall morbidity in the study was low, and no significant differences in complications, e.g., bleeding were noted.

Bronchopulmonary dysplasia (or subglottic stenosis?).

Bronchopulmonary dysplasia has now become the most common chronic lung disease of early childhood, and is a sequel of neonatal intensive care. The condition is characterized by interstitial fibrosis, agenesis of pulmonary alveoli, and distension of the remaining lung tissue. The resultant stiffness of the lung leads to noisy, labored respiration with retraction of the soft tissues of the thorax during inspiration which may easily be mistaken for the signs of subglottic stenosis. Two cases which illustrate the problem are presented. The mechanism underlying the clinical picture is discussed.

Dilator naris muscle.

The human nose is an important organ of respiration which by virtue of its valvular influence becomes a significant effector of respiratory resistance over a wide range of ventilatory requirements. In man its effectiveness in this regard is related to its flow limiting segment (FLS) located at the limen nasi. Its passive valvular effect is additionally modified by active respiratory contractions of the dilator naris muscle (DNM) controlled through the VII cranial nerve by the brain stem respiratory center. Its behavior, quantitatively determined in human beings and experimental animals, is summarized. 1) In man, phasic DNM activity operates during eupneic nasal breathing and varies directly with ventilatory resistance. 2) The elimination of all measurable ventilatory resistance results in complete cessation of DNM activity. 3) Over time, reduced resistance produces difficulty in reestablishing dilator function once it is physiologically lost. 4) DNM respiratory activity is modified by pulmonary mechano- and pressure-receptors via afferent vagal pathways. The response of nasal dilators in valvular control, therefore, appears dependent on the physiologic integrity of the vagus nerves. It is our belief that nasal valvular control has not previously been appreciated in this context.

Dilator naris function: a useful test of facial nerve integrity.

The dilator naris muscle is an active participant of respiration in man. Its level of function appears to vary directly with ventilatory resistance. Three cases are reported to illustrate the use of the respiratory function of this muscle as a clinical test of seventh nerve integrity when its volitional function cannot be elicited.