Congenital diaphragmatic hernia treated via fetal endoscopic tracheal occlusion improves outcome in a middle-income country.

OBJECTIVES: A recent European randomized trial - Tracheal Occlusion To Accelerate Lung Growth - demonstrated that fetoscopic endoluminal tracheal occlusion (FETO) is associated with increased postnatal survival among infants with severe congenital diaphragmatic hernia (CDH). However, this differs in middle-income countries such as Brazil, where abortion is illegal and neonatal intensive care is inadequate. This study evaluated the effects of FETO on improving the survival of infants with moderate-to-severe CDH in isolated and non-isolated cases. METHODS: This retrospective cohort study selected 49 fetuses with CDH, a normal karyotype, and a lung-to-head ratio (LHR) of <1 from a single national referral center for fetal surgery in São Paulo, Brazil, between January 2016 and November 2019. FETO was performed between 26 and 29 weeks of gestation. The primary outcomes were infant survival until discharge from the neonatal intensive care unit and survival until six months of age. RESULTS: Forty-six women with singleton fetuses having severe CDH underwent prenatal intervention with FETO. Infant survival rates until discharge and at six months of age were both 38 %. The observed-to-expected LHR increased by 25 % after FETO in neonates who survived until discharge. Spontaneous intrauterine death occurred in four growth-restricted fetuses after FETO. Preterm birth in <37 weeks and preterm rupture of membranes in <34 weeks occurred in 56.5 % (26) and 26 % (12) cases, respectively. CONCLUSIONS: FETO may increase neonatal survival in fetuses with severe CDH, particularly in countries with limited neonatal intensive care.

Assessment of Human Fetuses Undergoing Acute Pain: Validation of the Fetal-7 Scale.

Improvements in fetal ultrasound have allowed for the diagnosis and treatment of fetal diseases in the uterus, often through surgery. However, little attention has been drawn to the assessment of fetal pain. To address this gap, a fetal pain scoring system, known as the Fetal-7 scale, was developed. The present study is a full validation of the Fetal-7 scale. The validation involved 2 steps: 1) 4 fetuses with the indication of surgery were evaluated in 3 conditions perioperatively: acute pain, rest, and under loud sound stimulation. Facial expressions were assessed by 30 raters using screenshots from 4D high-definition ultrasound films; 2) assessment of sensitivity and specificity of the Fetal-7 scale in 54 healthy fetuses and 2 fetuses undergoing acute pain after preoperative anesthetic intramuscular injection. There was high internal consistency with Cronbach's alpha (α) of .99. Intrarater reliability of the Fetal-7 scale (test-retest) calculated by intraclass correlation coefficient was .95, and inter-rater reliability was .99. The scale accurately differentiated between healthy fetuses at rest and those experiencing acute pain (sensitivity of 100% and specificity of 94.4%). The Fetal-7 scale is a valid tool for assessing acute pain-related behavior in third-trimester fetuses and may be of value in guiding analgesic procedures efficacy in these patients. Further research is warranted to explore the presence of postoperative pain in fetuses and its effects after birth. PERSPECTIVE: Recordings with 3-dimensional ultrasound of human fetuses undergoing preoperative anesthetic injections revealed complex facial expressions during acute pain, similar to those collected in newborns. This study presented the validation process and cut-off value of the Fetal-7 scale, paving the way for the study of pain before birth in humans.

Sorting pain out of salience: assessment of pain facial expressions in the human fetus.

INTRODUCTION: The question of whether the human fetus experiences pain has received substantial attention in recent times. With the advent of high-definition 4-dimensional ultrasound (4D-US), it is possible to record fetal body and facial expressions. OBJECTIVE: To determine whether human fetuses demonstrate discriminative acute behavioral responses to nociceptive input. METHODS: This cross-sectional study included 5 fetuses with diaphragmatic hernia with indication of intrauterine surgery (fetoscopic endoluminal tracheal occlusion) and 8 healthy fetuses, who were scanned with 4D-US in 1 of 3 conditions: (1) acute pain group: Fetuses undergoing intrauterine surgery were assessed in the preoperative period during the anesthetic injection into the thigh; (2) control group at rest: Facial expressions at rest were recorded during scheduled ultrasound examinations; and (3) control group acoustic startle: Fetal facial expressions were recorded during acoustic stimulus (500-4000 Hz; 60-115 dB). RESULTS: Raters blinded to the fetuses' groups scored 65 pictures of fetal facial expressions based on the presence of 12 items (facial movements). Analyses of redundancy and usefulness excluded 5 items for being of low discrimination capacity (P>0.2). The final version of the pain assessment tool consisted of a total of 7 items: brow lowering/eyes squeezed shut/deepening of the nasolabial furrow/open lips/horizontal mouth stretch/vertical mouth stretch/neck deflection. Odd ratios for a facial expression to be detected in acute pain compared with control conditions ranged from 11 (neck deflection) to 1,400 (horizontal mouth stretch). Using the seven-item final tool, we showed that 5 is the cutoff value discriminating pain from nonpainful startle and rest. CONCLUSIONS: This study inaugurates the possibility to study pain responses during the intrauterine life, which may have implications for the postoperative management of pain after intrauterine surgical interventions.

COL1A1, COL4A3, TIMP2 and TGFB1 polymorphisms in cervical insufficiency.

OBJECTIVES: To investigate the association between selected single nucleotide polymorphisms (SNPs) with cervical insufficiency and its relationship with obstetric history. METHODS: Twenty-eight women with cervical insufficiency (case group) and 29 non-pregnant women (control group) were included. The SNPs sequenced included rs2586490 in collagen type I alpha 1 chain (COL1A1), rs1882435 in collagen type IV alpha 3 chain (COL4A3), rs2277698 in metallopeptidase inhibitor 2 (TIMP2), and rs1800468 in transforming growth factor beta 1 (TGFB1). RESULTS: We found a higher frequency of the normal allele in the control group (65.5%) and the homozygous mutated genotype in the case group (64.3%) for rs2586490 in COL1A1 (p=0.023). An unplanned finding in the cervical insufficiency group was a higher gestational age of delivery (median≥38 weeks) in the mutated allele than in the wild-type genotype (median of 28.2 weeks) for rs2857396, which is also in the COL1A1 gene (p=0.011). CONCLUSIONS: The findings of the present study corroborate the hypothesis that cervical insufficiency has a genetic component and probably involves genes encoding proteins in the extracellular matrix, in addition to inflammatory processes.