Characteristics of preterm births during COVID-19 mitigation measures.

BACKGROUND: During the COVID-19 pandemic, mitigation measures were associated with a reduction in preterm birth rates; while not clearly proven, this observation has sparked significant interest. AIM: To understand the cause of this reduction by exploring the characteristics of preterm birth cohorts. MATERIAL AND METHODS: We performed a retrospective cohort study where we compared women who delivered preterm in three Melbourne maternity hospitals and conceived between November 2019 and February 2020 (mitigation measures-exposed cohort) to women who delivered preterm and conceived between November 2018 and February 2019 (non-exposed cohort). We compared maternal characteristics, pregnancy complications, antenatal interventions, intrapartum care, and indications for delivery. RESULTS: In the exposed cohort, 252/3129 women delivered preterm (8.1%), vs 298/3154 (9.4%) in the non-exposed cohort (odds ratio (OR) 0.84, 95% CI 0.70-1.00, P = 0.051). The baseline characteristic of two cohorts were comparable. Rates of spontaneous preterm labour (sPTL) without preterm pre-labour rupture of membranes (PPROM) were lower in the exposed cohort (13.1% vs 24.2%, OR 0.47, P = 0.001) while PPROM occurred more often (48.0% vs 35.6%, OR 1.67, P = 0.003). With a non-statistically significant prolongation of pregnancy in the cohort exposed to mitigation measures for both sPTL without PPROM (35.4 vs 34.9 weeks, P = 0.703) and PPROM (35.6 vs 34.9 weeks, P = 0.184). The rate of spontaneous labour after PPROM was higher in the exposed cohort compared to the non-exposed cohort (40.1% vs 24.1%, OR 2.09, P < 0.001). CONCLUSION: The reduction in preterm delivery during mitigation measures may have been driven by a reduction in spontaneous labour without PPROM, which seemed to result in more PPROM later in pregnancy.

Widespread implementation of a low-cost telehealth service in the delivery of antenatal care during the COVID-19 pandemic: an interrupted time-series analysis.

BACKGROUND: Little evidence is available on the use of telehealth for antenatal care. In response to the COVID-19 pandemic, we developed and implemented a new antenatal care schedule integrating telehealth across all models of pregnancy care. To inform this clinical initiative, we aimed to assess the effectiveness and safety of telehealth in antenatal care. METHODS: We analysed routinely collected health data on all women giving birth at Monash Health, a large health service in Victoria (Australia), using an interrupted time-series design. We assessed the impact of telehealth integration into antenatal care from March 23, 2020, across low-risk and high-risk care models. Allowing a 1-month implementation period from March 23, 2020, we compared the first 3 months of telehealth integrated care delivered between April 20 and July 26, 2020, with conventional care delivered between Jan 1, 2018, and March 22, 2020. The primary outcomes were detection and outcomes of fetal growth restriction, pre-eclampsia, and gestational diabetes. Secondary outcomes were stillbirth, neonatal intensive care unit admission, and preterm birth (birth before 37 weeks' gestation). FINDINGS: Between Jan 1, 2018, and March 22, 2020, 20 031 women gave birth at Monash Health during the conventional care period and 2292 women gave birth during the telehealth integrated care period. Of 20 154 antenatal consultations provided in the integrated care period, 10 731 (53%) were delivered via telehealth. Overall, compared with the conventional care period, no significant differences were identified in the integrated care period with regard to the number of babies with fetal growth restriction (birthweight below the 3rd percentile; 2% in the integrated care period vs 2% in the conventional care period, p=0·72, for low-risk care models; 5% in the integrated care period vs 5% in the conventional care period, p=0·50 for high-risk care models), number of stillbirths (1% vs 1%, p=0·79; 2% vs 2%, p=0·70), or pregnancies complicated by pre-eclampsia (3% vs 3%, p=0·70; 9% vs 7%, p=0·15), or gestational diabetes (22% vs 22%, p=0·89; 30% vs 26%, p=0·06). Interrupted time-series analysis showed a significant reduction in preterm birth among women in high-risk models (-0·68% change in incidence per week [95% CI -1·37 to -0·002]; p=0·049), but no significant differences were identified in other outcome measures for low-risk or high-risk care models after telehealth integration compared with conventional care. INTERPRETATION: Telehealth integrated antenatal care enabled the reduction of in-person consultations by 50% without compromising pregnancy outcomes. This care model can help to minimise in-person interactions during the COVID-19 pandemic, but should also be considered in post-pandemic health-care models. FUNDING: None.

Why Do the Fetal Membranes Rupture Early after Fetoscopy? A Review.

Iatrogenic preterm premature rupture of the fetal membranes (iPPROM) remains the Achilles' heel of keyhole fetal surgery (fetoscopy) despite significant efforts in preclinical models to develop new therapies. This limited success is partially due to incomplete understanding why the fetal membranes rupture early after fetoscopy and notable differences in membrane physiology between humans and domestic species. In this review, we summarize aspects of fetoscopy that may contribute to iPPROM, the previous efforts to develop new therapies, and limitations of preclinical models commonly used in fetal membrane research.

Postnatal middle cerebral artery Dopplers in growth-restricted neonates.

This prospective observational study compared the middle cerebral artery (MCA) Doppler characteristics of FGR neonates (N = 20) with abnormal antenatal Dopplers, with those of appropriately grown (AGA) neonates (N = 20), in the immediate postnatal period. MCA peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI) were measured on day 1 and day 3. MCA PSV and EDV values were not significantly different between FGR (mean (SD) gestation: 31.4 (3.1) weeks, weight 1205 (463) grams) and AGA (31.1 (3.0) weeks; 1668 (490) grams) groups, on day 1 and day 3. Both FGR (30.85 (10.02) vs. 42.12 (9.16) cm/s, p = 0.007) and AGA groups (31.77 (9.32) vs. 42.0 (8.98) cm/s, p = 0.001) showed a significant increase in MCA PSV, but only the FGR group showed significant increase in EDV values (7.01 (4.23) vs. 11.78 (4.98), p = 0.002) from day 1 to day 3. This was associated with significant differences in RI (0.72 (0.10) vs. 0.79 (0.07), p = 0.01) and PI (1.36 (0.47) vs. 1.73 (0.4), p = 0.01) values between FGR and AGA groups on day 3.Conclusion: Significant differences in MCA resistive and pulsatility indices were noted in the first few days of life of FGR neonates with abnormal antenatal Doppler as compared with AGA neonates. This may suggest a delayed transition or persistence of cerebral redistribution in FGR neonates.What is Known:• FGR infants have increased risk of neonatal morbidity and mortality, and long-term neuro-disabilities.• Antenatal Doppler Ultrasound is the most common modality used to assess fetal growth restriction.What is New:• Antenatally detected abnormal cerebral Dopplers may persist during the neonatal period in growth-restricted neonates.• Early cerebral Doppler values may be a useful marker to identify "at risk" growth-restricted neonates..

Balancing Patient Access to Fetoscopic Laser Photocoagulation for Twin-to-Twin Transfusion Syndrome With Maintaining Procedural Competence: Are Collaborative Services Part of the Solution?

The benefits of fetoscopic laser photocoagulation (FLP) for treatment of twin-to-twin transfusion syndrome (TTTS) have been recognized for over a decade, yet access to FLP remains limited in many settings. This means at a population level, the potential benefits of FLP for TTTS are far from being fully realized. In part, this is because there are many centers where the case volume is relatively low. This creates an inevitable tension; on one hand, wanting FLP to be readily accessible to all women who may need it, yet on the other, needing to ensure that a high degree of procedural competence is maintained. Some of the solutions to these apparently competing priorities may be found in novel training solutions to achieve, and maintain, procedural proficiency, and with the increased utilization of 'competence based' assessment and credentialing frameworks. We suggest an under-utilized approach is the development of collaborative surgical services, where pooling of personnel and resources can improve timely access to surgery, improve standardized assessment and management of TTTS, minimize the impact of the surgical learning curve, and facilitate audit, education, and research. When deciding which centers should offer laser for TTTS and how we decide, we propose some solutions from a collaborative model.

The use of intrapartum ultrasound in operative vaginal birth: a retrospective cohort study.

BACKGROUND: Poor outcomes from operative vaginal birth have been associated with failure to recognize malposition, breakdown in interdisciplinary communication, and deviation from accepted guidelines. We recently implemented a safety bundle including routine intrapartum ultrasound and a structured time-out and procedural checklist aiming to reduce maternal and perinatal morbidity from operative vaginal birth. OBJECTIVE: This study aimed to compare births where intrapartum ultrasound was used and those where it was not used during a safety bundle implementation period at Monash Health. STUDY DESIGN: We performed a retrospective cohort study at Monash Health during the transitional phase of implementing an operative vaginal birth safety bundle. We studied all women with operative vaginal birth and fully dilated cesarean delivery with a singleton cephalic term fetus. We compared births for which intrapartum ultrasound was used and those for which it was not. The primary outcome was neonates delivered in an unexpected position. Neonatal and maternal morbidity were also assessed, including a neonatal composite of Apgar score <7 at 5 minutes, cord lactate >8 mmol/L, need for resuscitation, significant birth trauma, or neonatal intensive care unit admission. To control for confounding by indication, we estimated propensity scores for the probability of using intrapartum ultrasound for each case based on maternal and labor characteristics, and adjusted the effect estimates for the propensity scores using multivariable logistic regression models. RESULTS: From August 2022 to July 2023, there were 1205 operative vaginal births or fully dilated cesarean deliveries at Monash Health, including 743 (61.7%) forceps, 346 (28.7%) vacuum, and 116 (9.6%) fully dilated cesarean deliveries. Over this time, we observed increased uptake of intrapartum ultrasound from 26% in August 2022 to 60% (P<.001) in July 2023, of the time-out from 21% to 58% (P<.001), and the checklist from 33% to 80% (P<.001) of operative second-stage births. Among the births where intrapartum ultrasound was used (n=509), compared with those where it was not (n=696), there were significantly more forceps births (67% vs 58%; adjusted odds ratio, 1.35; 95% confidence interval, 1.05-1.74; P=.021) and a reduction in vacuum births (24% vs 32%; adjusted odds ratio, 0.77; 95% confidence interval, 0.58-1.01; P=.059). There were no significant differences in fully dilated cesarean delivery or maternal morbidity. Intrapartum ultrasound use was associated with significantly fewer infants being delivered in an unexpected position (0.2% vs 2.2%; adjusted odds ratio, 0.08; 95% confidence interval, 0.00-0.44; P=.019) and a significant reduction in composite neonatal morbidity (22% vs 25%; adjusted odds ratio, 0.73; 95% confidence interval, 0.54-0.97; P=.031). CONCLUSION: During the implementation of a safety bundle, the use of ultrasound before operative vaginal birth was associated with fewer infants delivered in an unexpected position and reduced neonatal morbidity.

Surgical management of placenta accreta: a 10-year experience.

OBJECTIVE: To examine maternal morbidity in primary surgical management of placenta accreta. DESIGN: Retrospective case series. SETTING: Quaternary perinatal referral center in Melbourne, Australia. POPULATION: Clinically suspected and histologically confirmed cases of placenta accreta, increta and percreta. METHODS: Women were identified from our hospital database coded for placenta accreta, increta, percreta and peripartum hysterectomy. Relevant details were sought from medical records. MAIN OUTCOME MEASURES: Predefined maternal morbidities: blood loss, transfusion requirements, surgical complications, reoperation rate, duration in hospital. Predefined neonatal outcomes: gestational age at birth, birth-weight, admission to intensive (NICU) or special care nurseries (SCN), respiratory distress syndrome. RESULTS: Between 1999 and 2009, 33 women were diagnosised with invasive placentation. A total of 27 were confirmed histologically after hysterectomy: 12 accreta, one increta, and 14 percreta. Median blood loss was 2 L. There was a 1.8-L reduction in mean blood loss with elective vs. emergency hysterectomy (p = 0.04). Nearly two-thirds of women required four or more units of packed red-blood-cells. Half of the women suffered from surgical complications, mostly from bladder injury. The risk of returning to theater for further surgery was 20%. Women with placenta percreta were more likely to require additional blood products (p = 0.03), sustain renal tract injury (p = 0.003) and require intensive care admission (p = 0.002). CONCLUSIONS: A primary surgical approach to management of placenta accreta is associated with significant maternal morbidity, even when managed in a dedicated quaternary perinatal referral center.

Impact of cone-beam computed tomography on orthodontic diagnosis and treatment planning.

INTRODUCTION: In this study, we measured the impact of cone-beam computed tomography (CBCT) on orthodontic diagnosis and treatment planning. METHODS: Participant orthodontists shown traditional orthodontic records for 6 patients were asked to provide a diagnostic problem list, a hypothetical treatment plan, and a clinical certainty. They then evaluated a CBCT scan for each patient and noted any changes, confirmations, or enhancements to their diagnosis and treatment plan. RESULTS: The number of diagnosis and treatment plan changes varied widely by patient characteristics. The most frequently reported diagnosis and treatment plan changes occurred in patients with unerupted teeth, severe root resorption, or severe skeletal discrepancies. We found no benefit in terms of changes in treatment plan for patients when the reason for obtaining a CBCT scan was to examine for abnormalities of the temporomandibular joint or airway, or crowding. Orthodontic participants who own CBCT machines or use CBCT scans frequently in practice reported significantly more diagnosis and treatment plan changes and greater confidence after viewing the CBCT scans during the study. CONCLUSIONS: The results of this study support obtaining a CBCT scan before orthodontic diagnosis and treatment planning when a patient has an unerupted tooth with delayed eruption or a questionable location, severe root resorption as diagnosed with a periapical or panoramic radiograph, or a severe skeletal discrepancy. We propose that CBCT scans should be ordered only when there is clear, specific, individual clinical justification.

CO-Sprout-A Pilot Double-Blinded Placebo-Controlled Randomised Trial of Broccoli Sprout Powder Supplementation for Pregnant Women with COVID-19 on the Duration of COVID-19-Associated Symptoms: Study Protocol.

Since its discovery in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to be responsible for at least 769.3 million infections and over 6.95 million deaths. Despite significant global vaccination efforts, there are limited therapies that are considered safe and effective for use in the management of COVID-19 during pregnancy despite the common knowledge that pregnant patients have a much higher risk of adverse outcomes. A bioactive compound found in broccoli sprout-sulforaphane-is a potent inducer of phase-II detoxification enzymes promoting a series of potentially beneficial effects notably as an antioxidant, anti-inflammatory, and anti-viral. A pilot, double-blinded, placebo-controlled randomised trial is to be conducted in Melbourne, Australia, across both public and private hospital sectors. We will assess a commercially available broccoli sprout extract in pregnant women between 20+0 and 36+0 weeks gestation with SARS-CoV-2 infection to investigate (i) the duration of COVID-19 associated symptoms, (ii) maternal and neonatal outcomes, and (iii) biomarkers of infection and inflammation. We plan to enrol 60 outpatient women with COVID-19 irrespective of vaccination status diagnosed by PCR swab or RAT (rapid antigen test) within five days and randomised to 14 days of oral broccoli sprout extract (42 mg of sulforaphane daily) or identical microcrystalline cellulose placebo. The primary outcome of this pilot trial will be to assess the feasibility of conducting a larger trial investigating the duration (days) of COVID-19-associated symptoms using a broccoli sprout supplement for COVID-19-affected pregnancies. Pregnant patients remain an at-risk group for severe disease following infection with SARS-CoV-2 and currently unclear consequences for the offspring. Therefore, this study will assess feasibility of using a broccoli sprout supplement, whilst providing important safety data for the use of sulforaphane in pregnancy.

Human amnion epithelial cells reduce ventilation-induced preterm lung injury in fetal sheep.

OBJECTIVE: The objective of the study was to explore whether human amnion epithelial cells (hAECs) can mitigate ventilation-induced lung injury. STUDY DESIGN: An established in utero ovine model of ventilation-induced lung injury was used. At day 110 of gestation, singleton fetal lambs either had sham in utero ventilation (IUV) (n = 4), 12 hours of IUV alone (n = 4), or 12 hours of IUV and hAEC administration (n = 5). The primary outcome, structural lung injury, was assessed 1 week later. RESULTS: Compared with sham controls, IUV alone was associated with significant lung injury: increased collagen (P = .03), elastin (P = .02), fibrosis (P = .02), and reduced secondary-septal crests (P = .009). This effect of IUV was significantly mitigated by the administration of hAECs: less collagen (P = .03), elastin (P = .04), fibrosis (P = .02), normalized secondary-septal crests (P = .02). The hAECs were immunolocalized within the fetal lung and had differentiated into type I and II alveolar cells. CONCLUSION: The hAECs mitigate ventilation-induced lung injury and differentiated into alveolar cells in vivo.

Acceptability of stem cell therapy by pregnant women.

BACKGROUND: Cell-based therapies may soon be used to treat disorders in the perinatal period. Our aim was to assess pregnant women's knowledge, attitudes, and acceptance of different types of stem cell therapies. METHODS: Pregnant women attending an Australian tertiary center were asked to complete a questionnaire to seek their views on the potential therapeutic use of stem cells in the future. Outcome measures were women's acceptability of different types of stem cell therapies for themselves and their baby, ethical concerns, knowledge, and willingness to use stem cells for different indications. RESULTS: A total of 150 women completed the questionnaire. More women were happy to use any stem cell type (82%) than placental stem cells only (12.5%), adult stem cells only (2%), embryonic stem cells only (0), and 3.5 percent would not use. With respect to use for their baby, more women were happy to use any stem cell type (83%) than placental stem cells only (13%), embryonic stem cells only (2%), adult stem cells only (0), and 2 percent would not use. Ethical concerns were highest with embryonic stem cells (25%), than adult stem cells (11%), and placental stem cells (10%). Twelve percent of women were very confident and 66 percent reasonably confident with their knowledge, whereas 17 percent understood little and 5 percent reported no understanding. Acceptance of using any stem cell therapy was 75 percent for severe medical disorders, 57 percent for moderate disorders, and 25 percent for mild medical disorders. CONCLUSIONS: Pregnant women are confident with their knowledge of stem cells and overwhelmingly support their use to treat both themselves and their baby. The level of this support, however, is proportionate to the severity of the medical disorder. (BIRTH 39:2 June 2012).

The kindness COVID-19 toolkit: a mixed-methods evaluation of a programme designed by doctors in training for doctors in training.

OBJECTIVES: The impact of a coronavirus disease (COVID-19)-specific professional development programme on the well-being of obstetrics and gynaecology (O&G) doctors in training (DiT) working during the pandemic. DESIGN: A mixed-method evaluation of a single group pre-post test design study. SETTING: Melbourne, Australia between September 2020 and April 2021. PARTICIPANTS: 55 O&G DiT working across four healthcare sites of a major tertiary hospital in Victoria, Australia, were included in the programme. INTERVENTIONS: The delivery of a codesigned peer-to-peer programme, which identified and addressed the well-being goals of O&G DiT. Seven interactive workshops were run alongside the implementation of a number of participant-led wellness initiatives. MAIN OUTCOME MEASURES: Repeated-measures analysis of WHO Well-being Index (WHO-5) and Copenhagen Burnout Innovatory (CBI) scores across three time points during the programme. Multilevel generalised linear mixed-effects models with random intercept were fit to the data, both in the entire population (intention-to-treat) and restricted to those who attended the workshop ('per-protocol' analysis). Participatory experiences and programme learning were captured using the Most Significant Change (MSC) technique, which included inductive thematic analysis. RESULTS: We demonstrated an overall 31.9% improvement in well-being scores (p=0.006). The MSC evaluation captured a shift in workplace culture as a result of the programme, with improvement across the domains of connection, caring, communication, confidence and cooperation. CONCLUSIONS: We have successfully used a mixed-method approach to contextualise a productive programme to improve the well-being of COVID-19 front-line healthcare workers.

Human amnion epithelial cells as a treatment for inflammation-induced fetal lung injury in sheep.

OBJECTIVE: The purpose of this study was to determine whether human amnion epithelial cells (hAECs) can modulate the pulmonary developmental consequences of intrauterine inflammation in fetal sheep that are exposed to intraamniotic lipopolysaccharide (LPS) injection. STUDY DESIGN: At 117 days' gestation, fetal sheep (n=16) received intraamniotic LPS (20 mg). hAECs were delivered at 0, 6, and 12 hours into the fetal jugular vein (n=4), trachea (n=4), or both (n=4). Controls (n=6) received equivalent administration of saline solution. Lungs were collected at 124 days. RESULTS: Intraamniotic LPS caused pulmonary inflammation and altered lung structure and function. hAECs attenuated changes in lung function and structure that had been induced by LPS: lung volume, 40 cm H2O (P<.05, intravenous+intratracheal hAECs vs LPS), tissue-to-airspace ratio (P<.05, intravenous+intratracheal hAECs vs LPS), and septal crest density (P<.001, all hAEC groups vs LPS). Leukocyte infiltration of the lungs was not reduced by hAECs; however, inflammatory cytokines were reduced (tumor necrosis factor-α, P<.01, vs LPS; interleukin-1b, P<.01, vs LPS; interleukin-6, P<.01 vs LPS). Surfactant protein A and C messenger RNA was increased by LPS, although this was not statistically significant (P>.05 vs control); there were significant increases in all hAEC-treated animals (surfactant protein-A, P<.05 vs LPS; surfactant protein-C, P<.01 vs LPS). CONCLUSION: Human amnion epithelial cells attenuate the fetal pulmonary inflammatory response to experimental intrauterine inflammation and reduce, but (as administered in our study) do not prevent, consequent alterations in lung development.

Coronavirus testing in women attending antenatal care.

BACKGROUND: Universal screening has been proposed as a strategy to identify asymptomatic individuals infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mitigate transmission. AIM: To investigate the rate of positive tests among pregnant women in Melbourne, Australia. METHODS: We performed a cross-sectional prevalence study at three maternity hospitals (one tertiary referral hospital and two secondary maternities) in Melbourne, Australia. SARS-CoV-2 testing was offered to all pregnant women attending face-to-face antenatal visits and to those attending the hospital with symptoms of possible coronavirus disease, between 6th and 19th of May 2020. Testing was performed by multiplex-tandem polymerase chain reaction (PCR) on combined oropharyngeal and nasopharyngeal swabs. The primary outcome was the proportion of positive SARS-CoV-2 tests. FINDINGS: SARS-CoV-2 testing was performed in 350 women, of whom 19 had symptoms of possible COVID-19. The median maternal age was 32 years (IQR 28-35 years), and the median gestational age at testing was 33 weeks and four days (IQR 28 weeks to 36 weeks and two days). All 350 tests returned negative results (p̂=0%, 95% CI 0-1.0%). CONCLUSION: In a two-week period of low disease prevalence, the rate of asymptomatic coronavirus infection among pregnant women in Australia during the study period was negligible, reflecting low levels of community transmission.

Physiologic-Based Cord Clamping Maintains Core Temperature vs. Immediate Cord Clamping in Near-Term Lambs.

Background: Physiologic-based cord clamping (PBCC) involves deferring umbilical cord clamping until after lung aeration. It is unclear if infant is at risk of becoming hypothermic during PBCC. Objectives: To test if PBCC would maintain core temperature more effectively than immediate cord clamping (ICC). Design: At 0.93 gestation, fetal lambs were surgically exteriorized and instrumented from pregnant ewes under general anesthesia. Prior to the start of the experiment, lambs were thoroughly dried, placed on hot water bottles, and core temperature was continuously monitored using a rectal thermometer. PBCC lambs (n = 21), received intermittent positive pressure ventilation (iPPV) for ≥5 min prior to umbilical cord clamping. In ICC lambs (n = 23), iPPV commenced within 60 s after umbilical cord clamping. iPPV was provided with heated/humidified gas. Lambs were moved under a radiant warmer after umbilical cord clamping. Additional warmth was provided using a plastic overlay, hairdryer, and extra water bottles, as needed. Two-way mixed and repeated measures one-way ANOVAs were used to compare temperature changes between and within a single group, respectively, over time. Results: Basal fetal parameters including core temperature were similar between groups. ICC lambs had a significant reduction in temperature compared to PBCC lambs (p < 0.001), evident by 1 min (p = 0.002). ICC lambs decreased temperature by 0.51°C (± 0.42) and 0.79°C (± 0.55) at 5 and 10 min respectively (p < 0.001). In PBCC lambs, temperature did not significantly change before or after umbilical cord clamping (p = 0.4 and p = 0.3, respectively). Conclusions: PBCC stabilized core temperature at delivery better than ICC in term lambs. Hypothermia may not be a significant risk during PBCC.

Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia.

OBJECTIVE: Lung hypoplasia associated with congenital diaphragmatic hernia (CDH) results in respiratory insufficiency and pulmonary hypertension after birth. We have investigated whether aerating the lung before removing placental support (physiologically based cord clamping (PBCC)), improves the cardiopulmonary transition in lambs with a CDH. METHODS: At ≈138 days of gestational age, 17 lambs with surgically induced left-sided diaphragmatic hernia (≈d80) were delivered via caesarean section. The umbilical cord was clamped either immediately prior to ventilation onset (immediate cord clamping (ICC); n=6) or after achieving a target tidal volume of 4 mL/kg, with a maximum delay of 10 min (PBCC; n=11). Lambs were ventilated for 120 min and physiological changes recorded. RESULTS: Pulmonary blood flow (PBF) increased following ventilation onset in both groups, but was 19-fold greater in PBCC compared with ICC lambs at cord clamping (19±6.3 vs 1.0±0.5 mL/min/kg, p<0.001). Cerebral tissue oxygenation was higher in PBCC than ICC lambs during the first 10 min after cord clamping (59%±4% vs 30%±5%, p<0.001). PBF was threefold higher (23±4 vs 8±2 mL/min/kg, p=0.01) and pulmonary vascular resistance (PVR) was threefold lower (0.6±0.1 vs 2.2±0.6 mm Hg/(mL/min), p<0.001) in PBCC lambs compared with ICC lambs at 120 min after ventilation onset. CONCLUSIONS: Compared with ICC, PBCC prevented the severe asphyxia immediately after birth and resulted in a higher PBF due to a lower PVR, which persisted for at least 120 min after birth in CDH lambs.

Effects of tracheal occlusion on the neonatal cardiopulmonary transition in an ovine model of diaphragmatic hernia.

OBJECTIVE: Fetoscopic endoluminal tracheal occlusion (FETO) aims to reverse pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) and mitigate the associated respiratory insufficiency and pulmonary hypertension after birth. We aimed to determine whether FETO improves the cardiopulmonary transition at birth in an ovine model of CDH. METHODS: In 12 ovine fetuses with surgically induced diaphragmatic hernia (DH; 80 dGA), an endotracheal balloon was placed tracheoscopically at ≈110 dGA and removed at ≈131 dGA (DH+FETO), while 10 were left untreated (DH). At ≈138 dGA, all lambs (survival at delivery: 67% [DH+FETO], 70% [DH]) were delivered via caesarean section and ventilated for 2 hours. Physiological and ventilation parameters were continuously recorded, and arterial blood-gas values were measured. RESULTS: Compared with DH, DH+FETO lambs had increased wet lung-to-body-weight ratio (0.031±0.004 vs 0.016±0.002) and dynamic lung compliance (0.7±0.1 vs 0.4±0.1 mL/cmH2O). Pulmonary vascular resistance was lower in DH+FETO lambs (0.44±0.11 vs 1.06±0.17 mm Hg/[mL/min]). However, after correction for lung weight, pulmonary blood flow was not significantly different between the groups (4.19±0.57 vs 4.05±0.60 mL/min/g). Alveolar-arterial difference in oxygen tension was not significantly different between DH+FETO and DH (402±41mm Hg vs 401±45 mm Hg). CONCLUSIONS: FETO accelerated lung growth in fetuses with CDH and improved neonatal respiratory function during the cardiopulmonary transition at birth. However, despite improved lung compliance and reduced pulmonary vascular resistance, there were less pronounced benefits for gas exchange during the first 2 hours of life.

Neonatal cardiopulmonary transition in an ovine model of congenital diaphragmatic hernia.

OBJECTIVE: Infants with a congenital diaphragmatic hernia (CDH) are at high risk of developing pulmonary hypertension after birth, but little is known of their physiological transition at birth. We aimed to characterise the changes in cardiopulmonary physiology during the neonatal transition in an ovine model of CDH. METHODS: A diaphragmatic hernia (DH) was surgically created at 80 days of gestational age (dGA) in 10 fetuses, whereas controls underwent sham surgery (n=6). At 138 dGA, lambs were delivered via caesarean section and ventilated for 2 hours. Physiological and ventilation parameters were continuously recorded, and arterial blood gas values were measured. RESULTS: DH lambs had lower wet lung-to-body-weight ratio (0.016±0.002vs0.033±0.004), reduced dynamic lung compliance (0.4±0.1mL/cmH2O vs1.2±0.1 mL/cmH2O) and reduced arterial pH (7.11±0.05vs7.26±0.05), compared with controls. While measured pulmonary blood flow (PBF) was lower in DH lambs, after correction for lung weight, PBF was not different between groups (4.05±0.60mL/min/gvs4.29±0.57 mL/min/g). Cerebral tissue oxygen saturation was lower in DH compared with control lambs (55.7±3.5vs67.7%±3.9%). CONCLUSIONS: Immediately after birth, DH lambs have small, non-compliant lungs, respiratory acidosis and poor cerebral oxygenation that reflects the clinical phenotype of human CDH. PBF (indexed to lung weight) was similar in DH and control lambs, suggesting that the reduction in PBF associated with CDH is proportional to the degree of lung hypoplasia during the neonatal cardiopulmonary transition.

A Randomized Double-Blinded Placebo-Controlled Intervention Trial of Melatonin for the Prevention of Preeclampsia in Moderate- and High-Risk Women: The MELPOP Trial.

This chapter describes the methodologies which may be used in the development of a randomized controlled trial investigating a therapy of choice in preventing preeclampsia.