Telehealth and Technology for Diabetes in Pregnancy Clinics: Staff Perspectives from South Auckland, New Zealand.

Providing care for patients with diabetes in pregnancy (DiP) provides unique challenges beyond those faced in standard antenatal care or diabetes outside of pregnancy. Teleclinics (use of telephone, email, or other technologies) as an alternative to in-person clinic appointments have become more widely used for care since the start of the COVID-19 pandemic. To understand how teleclinics might be improved for ongoing use, it is important to understand the experiences and perceptions of the clinicians involved in DiP care. Aim. To understand staff experiences of DiP teleclinics and gain their perspectives on if and how teleclinics and other technologies might be best used in the future. Methods. A qualitative study using semistructured interviews of healthcare providers in a large DiP service. Twenty staff members (midwifery, obstetrics, physician, dietician, and administration) were approached to participate. Fifteen staff across 5 specialties consented to be interviewed. Template analysis of interview transcripts was performed, with a focus on 3 themes: collaboration and working together are important for providing care for DiP, a need for flexibility in scheduling and the ability to individualise the way care is provided, and challenges to adapting to new technology. Results. Potential benefits of teleclinics were acknowledged, but respondents also viewed teleclinics as not suitable for all DiP patients due to different needs and risks. Challenges to using teleclinics include establishing good rapport and the current limited infrastructure and patient resources. Conclusion. Healthcare providers viewed teleclinics as a way of supporting rather than replacing current care. Maintaining flexibility in clinic scheduling to allow incorporation of teleclinics into patient's current schedule of visits ad hoc and providing extra technical and administrative support are important considerations for developing a teleclinic service.

Diabetes in pregnancy: Women's views of care in a multi-ethnic, low socioeconomic population with midwifery continuity-of-care.

BACKGROUND: Diabetes in pregnancy is diagnosed in 6% of pregnancies annually in Aotearoa-New Zealand, disproportionately affecting multi-ethnic, low socio-economic women. Little is known about the care experience of this population within the model of midwifery continuity-of-care, including views of telehealth care. AIM: Increase understanding of the experience of diabetes in pregnancy care, including telehealth, among multi-ethnic, low socio-economic women receiving midwifery continuity-of-care. METHODS: Qualitative interview study with primarily indigenous and migrant women who had diabetes in pregnancy and gave birth 6-18 months previously. Interviewers were matched with participants by ethnicity. Transcripts were analysed using Framework analysis. RESULTS: Participants were 19 women (5 Maori, 5 Pacific Peoples, 5 Asian, 4 European). Data analysis revealed three key themes: 1) 'shock, shame, and adjustment' to the diagnosis 2) 'learning to manage diabetes in pregnancy' and 3) 'preparation for birth and beyond' to the postpartum period. DISCUSSION: Receiving the diagnosis of diabetes in pregnancy was a shock. Managing diabetes during pregnancy was particularly challenging for indigenous and migrant women, who wished for better access to culturally appropriate dietary and lifestyle information. Women appreciated having options of telehealth and face-to-face consultations. Preparation for birth and postpartum diabetes follow-up were areas requiring significant improvement. Challenges were mitigated through care from a consistent diabetes specialist midwife and community-based midwifery continuity-of-care. CONCLUSION: Midwives were the backbone of diabetes in pregnancy care for this multi-ethnic, low socio-economic population. Care could be improved with more culturally appropriate diet and lifestyle information, better birth preparation, and expanded postpartum diabetes support.

The fatigue after infusion or transfusion pilot trial and feasibility study: A three-armed randomized pilot trial of intravenous iron and blood transfusion for the treatment of postpartum anemia.

BACKGROUND: Evidence for the management of moderate-to-severe postpartum anemia is limited. A randomized trial is needed; recruitment may be challenging. STUDY DESIGN AND METHODS: Randomized pilot trial with feasibility surveys. INCLUSION: hemoglobin 65-79 g/L, ≤7 days of birth, hemodynamically stable. EXCLUSION: ongoing heavy bleeding; already received, or contraindication to intravenous (IV)-iron or red blood cell transfusion (RBC-T). Intervention/control: IV-iron; RBC-T; or IV-iron and RBC-T. PRIMARY OUTCOME: number of recruits; proportion of those approached; proportion considered potentially eligible. SECONDARY OUTCOMES: fatigue, depression, baby-feeding, and hemoglobin at 1, 6 and 12 weeks; ferritin at 6 and 12 weeks. Surveys explored attitudes to trial participation. RESULTS: Over 16 weeks and three sites, 26/34 (76%) women approached consented to trial participation, including eight (31%) Maori women. Of those potentially eligible, 26/167 (15.6%) consented to participate. Key participation enablers were altruism and study relevance. For clinicians and stakeholders the availability of research assistance was the key barrier/enabler. Between-group rates of fatigue and depression were similar. Although underpowered to address secondary outcomes, IV-iron and RBC-T compared with RBC-T were associated with higher hemoglobin concentrations at 6 (mean difference [MD] 11.7 g/L, 95% confidence interval [CI] 2.7-20.7) and 12 (MD 12.8 g/L, 95% CI 1.5-24.2) weeks, and higher ferritin concentrations at 6 weeks (MD 136.8 mcg/L, 95% CI 76.6-196.9). DISCUSSION: Willingness to participate supports feasibility for a future trial assessing the effectiveness of IV-iron and RBC-T for postpartum anemia. Dedicated research assistance will be critical to the success of an appropriately powered trial including women-centered outcomes.

Inequities in pre-pregnancy folic acid use in Central and South Auckland: secondary analysis from a postpartum contraception survey.

Introduction In Aotearoa New Zealand (NZ), there is inequity in rates of neural tube defects (NTDs). Among Maaori, NTD occur in 4.58/10 000 live births, and for Pacific peoples, it is 4.09/10 000 live births; this is compared to 2.81/10 000 live births for non-Maaori, non-Pacific peoples. Aim To describe self-reported pre-pregnancy folic acid supplementation and to determine the association between pregnancy intendedness, ethnicity, parity, maternal age, care provider and pre-pregnancy folic acid supplementation. Methods Secondary analysis of postpartum survey data collected at Te Whatu Ora Te Toka Tumai and Counties Manukau birthing facilities in 2020 was conducted. Descriptive analyses explored pregnancy intendedness and self-reported folic acid use by demographic variables. Multivariable logistic regression explored independent associations between demographic variables and folic acid use among intended pregnancies. Results In total, 398 participants completed the survey. The response rate was (140/149) 94% at Counties Manukau and (258/315) 82% at Te Toka Tumai. Pre-pregnancy supplementation was reported by 182 of 398 participants (46%). Use was higher among those who intended their pregnancy (151/262, 58%) compared to those who were 'pregnancy ambivalent' (9/33, 27%) or did not intend to become pregnant (22/103, 21%). Factors independently associated with supplementation among intended pregnancies included: 'Other ethnicity' (European, Middle Eastern, Latin American, African) compared to Maaori (aOR 5.3 (95% CI 1.3, 21.8)), age ≥30 years compared to Discussion Low rates of pre-pregnancy folic acid supplementation exist in Auckland with significant ethnic disparity. Mandatory fortification of non-organic wheat is important, but supplementation is still recommended to maximally reduce risk.

Normotensive placental extracellular vesicles provide long-term protection against hypertension and cardiovascular disease.

BACKGROUND: Women with normotensive pregnancy are at a reduced risk of developing cardiovascular disease postpartum compared with those who experience hypertensive conditions during pregnancy. However, the underlying mechanisms remain poorly understood. During normotensive pregnancy, vast numbers of placental extracellular vesicles are released into the maternal circulation, which protect endothelial cells from activation and alter maternal vascular tone. We hypothesized that placental extracellular vesicles play a mechanistic role in lowering the risk of cardiovascular disease following normotensive pregnancy. OBJECTIVE: This study aimed to investigate the long-term effects of placental extracellular vesicles derived from normotensive term placentae on the cardiovascular system and explore the mechanisms underlying their biological effects. STUDY DESIGN: Spontaneously hypertensive rats were injected with placental extracellular vesicles from normotensive term pregnancies (2 mg/kg each time, n=8) or vehicle control (n=9) at 3 months of age. Blood pressure and cardiac function were regularly monitored from 3 months to 15 months of age. The response of mesenteric resistance arteries to vasoactive substances was investigated to evaluate vascular function. Cardiac remodeling, small artery remodeling, and renal function were investigated to comprehensively assess the impact of placental extracellular vesicles on cardiovascular and renal health. RESULTS: Compared with vehicle-treated control animals, rats treated with normotensive placental extracellular vesicles exhibited a significantly lower increase in blood pressure and improved cardiac function. Furthermore, the vasodilator response to the endothelium-dependent agonist acetylcholine was significantly enhanced in the normotensive placental extracellular vesicle-treated spontaneously hypertensive rats compared with the control. Moreover, treatment with placental extracellular vesicles reduced wall thickening of small renal vessels and attenuated renal fibrosis. CONCLUSION: Placental extracellular vesicles from normotensive term pregnancies have long-lasting protective effects reducing hypertension and mitigating cardiovascular damage in vivo.

How well do we support whanau with postpartum contraception? Comparison of two Auckland maternity hospitals.

AIM: To compare the rates of recall of contraceptive discussion and provision of chosen contraceptive method before discharge among patients who recently birthed in two tertiary maternity units in Auckland, New Zealand. METHOD: A cross-sectional survey of recently postpartum patients at tertiary and associated primary birthing units aligned with Auckland and Counties Manukau maternity services was undertaken in 2019 and 2020. RESULTS: Five hundred and seventy-one patients took part in the survey. Overall recall around contraceptive discussions was low, as was the number of patients leaving hospital with their preferred method of contraception. Compared to Counties Manukau, almost twice as many patients at Auckland were unable to recall either an antenatal or postpartum discussion with a health professional about contraception (77% vs 39%, p<0.001). Those birthing at Counties Manukau were also more likely to recall seeing a hospital contraceptive brochure than those at Auckland (42% vs 20%, p<0.001). Twice as many patients at Counties Manukau left hospital with their chosen method compared to those at Auckland (31% vs 14%, p<0.001). In addition, long-acting reversible contraceptives (LARCs) were more often chosen for contraception at Counties Manukau (31% vs 22%, p=0.01) and more patients left hospital with their LARC compared to Auckland (13% vs 7%, p=0.03). CONCLUSION: These differences between two large tertiary maternity services suggests an opportunity for quality improvement around contraception provision.

Factors associated with postpartum contraceptive planning in New Zealand.

OBJECTIVE: To identify factors associated with contraceptive planning in the immediate postpartum period. STUDY DESIGN: Survey of those receiving inpatient postpartum care in two tertiary hospitals/associated birthing units (Auckland, New Zealand). Multivariable analyses using logistic regression examined independent predictors of contraceptive planning. RESULTS: Of 571 participants, those who recalled both antenatal and postpartum contraception discussions were more likely to have a contraceptive plan than those who recalled neither (aOR 5.6(2.8-11.5)). CONCLUSION: Both antenatal and postpartum contraceptive discussions are associated with postpartum contraceptive planning. IMPLICATIONS: Both antenatal and postpartum discussions around contraception were independently associated with increased rates of established contraceptive plan postpartum, however patients who recalled both were more likely to have made a plan. Clinicians should provide multiple opportunities for discussing contraception throughout pregnancy and post-pregnancy to facilitate informed decision making.

Audit of cervical excision depth of large loop excision of the transformation zone procedures at Counties Manukau District Health Board.

AIMS: Cervical cancer is the fourth most common malignancy in females worldwide. Large loop excision of the transformation zone (LLETZ) procedures remain the preferred surgical technique to remove squamous cervical intraepithelial neoplasia (CIN) lesions globally. This study aimed to assess whether the depth of LLETZ procedures at Counties Manukau District Health Board (CMDHB) met established standards of care. METHODS: Hospital records were reviewed for all LLETZ procedures performed at CMDHB between 1 June 2020 to 3 May 2021, and these were compared to Public Health England's (PHE) 2020 Colposcopy Guidelines. RESULTS: One hundred and eighty-four cases were identified. Forty-eight percent of all LLETZ procedures were the correct excision depth relative to PHE's ≥95% threshold, primarily due to excisions being too shallow, particularly in patients with type 2 and 3 transformation zones (TZ), 48% and 86%, respectively. Maori and Pasifika patients represented only 16% and 13% of all LLETZ procedures in this study, respectively. CONCLUSIONS: This study identified significant oversampling of LLETZ excisions in patients with type 1 TZs, and significant under-sampling in patients with types 2 and 3 TZs. Ultimately, these findings highlight the need for additional quality improvement processes and emphasise the importance of auditing LLETZ procedures nationwide.

Teleclinics for the management of diabetes in pregnancy during COVID-19-maternal satisfaction and pregnancy outcomes.

AIMS: Diabetes in pregnancy (DiP) rates are increasing worldwide. Pasifika, Indian and Maori peoples have high rates of DiP any improvements in clinical care may be beneficial for these populations. During COVID-19 lockdowns, the DiP service in Counties Manukau Health (CMH) South Auckland switched from face-to-face appointments to teleclinics. This study aims to: determine satisfaction of pregnant people with teleclinics for DiP; compare clinical outcomes and attendance for those receiving care through teleclinics versus standard care; and compare rates of clinic attendance between face-to-face and teleclinic appointments. METHODS: A standardised questionnaire was completed by those who had attended a teleclinic. The primary outcome was a high score (4-5/5) for satisfaction and future use. A separate, retrospective study of clinical outcomes, and the number of appointments scheduled/attended were compared between all DiP patients who were scheduled an appointment during lockdown, and all of those who were scheduled appointments the year prior. RESULTS: Of the thirty-five participants who completed the survey (response rate 37%), 89% scored the clinic highly for satisfaction and future use. There were 179 patients scheduled to clinic during the period where teleclinics were the default model of care, and 187 patients scheduled to clinic the year prior. No differences in clinical outcomes were observed. Those receiving care during lockdown were offered more appointments, although attendance rates did not differ. CONCLUSION: Teleclinics for DiP are acceptable to the people we surveyed, but should be developed further so they better support the needs of those using them.

Postpartum anaemia in three New Zealand district health board regions: An observational study of incidence and management.

BACKGROUND: The incidence of postpartum anaemia (PPA) in New Zealand, and the extent of intravenous iron (IV-iron) use in its treatment, are unknown. AIMS: To report the incidence of PPA in three district health board (DHB) regions and describe current management of moderate to severe PPA, including by ethnicity. MATERIALS AND METHODS: Retrospective observational study of PPA (haemoglobin (Hb) <100 g/L) in three DHBs from July-December 2019. Cases with moderate to severe PPA (Hb <90 g/L) were reviewed and management compared to local and national guidance. Logistic regression examined demographic associations of PPA. RESULTS: There were 8849 women who gave birth during the study period: 4076 (46%) had postpartum Hb testing and 1544 (38%) had PPA. Of those tested, and after adjusting for deprivation and region, European women had lower adjusted odds ratios compared to Maori for being identified as having PPA (0.46, 95% CI 0.37-0.57, P < 0.01). Of 681 women with Hb <90 g/L, 278 (41%) received IV-iron only, 66 (10%) red blood cell transfusion (RBC-T) only and 155 (23%) both. Of those receiving RBC-T, 40/221 (18%) were actively bleeding. Maori (92/138, 67%) and Pacific (127/188, 68%) women with Hb <90 g/L had the highest incidence of IV-iron use. No guidelines provided recommendations for haemodynamically stable women without active bleeding. CONCLUSION: The incidence and management of PPA differs by ethnicity but fewer than half of the women had Hb testing, making precise determination of incidence impossible. The majority of women with Hb <90 g/L received IV-iron, with or without RBC-T.

Audit of waiting time-to-treatment of atypical endometrial hyperplasia.

BACKGROUND: Atypical endometrial hyperplasia (AEH) is the precursor lesion in endometrial carcinoma, the most common gynaecological malignancy in New Zealand, with inequities in disease burden and outcome for Maori and Pacific women. AIMS: In women diagnosed with AEH at two hospitals, to audit five standards of care for surgical management and time-to-treatment, and identify variation in care by ethnicity and other factors. MATERIALS AND METHODS: Demographic, referral, diagnostic and treatment characteristics were collected for women with a new AEH diagnosis between 1/1/2019 and 31/12/2020. Surgical management and time-to-treatment were audited against Royal College of Obstetricians and Gynaecologists and New Zealand Ministry of Health Faster Cancer Treatment recommendations. RESULTS: Of 124 participants, 60% were Pacific, 86% premenopausal, and 80% had obesity. For 55 women managed surgically, surgical standards of care were met. There were delays between referral, diagnosis and treatment - only 18% and 56% of women met the 62-day (referral to treatment) and 31-day (decision-to-treat to treatment) targets, respectively. Wait times were prolonged for women who had dilation and curettage (vs pipelle), magnetic resonance imaging (MRI) (vs no MRI), and surgery (vs medical management). Ethnic disparities were not identified for any standard. DISCUSSION: Delays to treatment were found throughout women's journeys. Hospital services can streamline their clinical pathways for women referred for abnormal uterine bleeding, flagging obesity as a high suspicion for cancer indicator, increasing access to endometrial sampling in primary care and establishing 'one-stop-shop' outpatient assessment with empiric initiation of intrauterine progestogen.

Pregnancy planning and barriers to accessing postnatal contraception in New Zealand.

OBJECTIVE: To estimate rates of pregnancy and contraceptive planning and to identify barriers and enablers to postnatal contraceptive use. STUDY DESIGN: Face-to-face survey of patients during their immediate postnatal stay at Middlemore Hospital, Auckland, or associated primary birthing units. Patients were approached by study investigators over designated 2-week study periods in 2019 and 2020. The primary outcome was the rate of pregnancy and contraceptive planning. The descriptive analysis explored differences between ethnicities. RESULTS: We were able to approach 332 of 497 eligible women (67%), and 313 of 332 (94%) of those who approached completed the survey. Fifty-three percent of pregnancies were reported to have been planned. Pregnancy was more often planned by European (72%), Indian (68%), and Other Asian patients (72%) compared with Maori (33%) and Pacific patients (39%) (p < 0.001). Thirty-seven percent of patients reported an antenatal contraceptive discussion, and these were more commonly reported by Maori and Pacific patients (p < 0.001). A quarter of patients reported never having a conversation about contraception during or immediately after pregnancy, a third of whom said they would have valued one. Fifty-nine percent of patients reported having made a contraceptive plan immediately after birth. Concern about the side effects of contraception was a barrier reported by 51% of patients. Cost, travel, finding time, and family views were less frequent barriers. CONCLUSION: Rates of pregnancy planning reported postnatally are consistent with previous NZ research at approximately 50%, and we also found ethnic differences. Concerns about side effects were the most significant barrier for patients accessing contraception and this needs to be addressed in a culturally useful format. IMPLICATIONS: Postpartum patients report low rates of pregnancy planning. A significant proportion of postpartum patients report having no conversations about contraception with clinicians, and concerns about side effects are their most common barrier to contraception.

Multiscale and multimodal imaging of utero-placental anatomy and function in pregnancy.

Placental structures at the nano-, micro-, and macro scale each play important roles in contributing to its function. As such, quantifying the dynamic way in which placental structure evolves during pregnancy is critical to both clinical diagnosis of pregnancy disorders, and mechanistic understanding of their pathophysiology. Imaging the placenta, both exvivo and invivo, can provide a wealth of structural and/or functional information. This review outlines how imaging across modalities and spatial scales can ultimately come together to improve our understanding of normal and pathological pregnancies. We discuss how imaging technologies are evolving to provide new insights into placental physiology across disciplines, and how advanced computational algorithms can be used alongside state-of-the-art imaging to obtain a holistic view of placental structure and its associated functions to improve our understanding of placental function in health and disease.

Pregnancy outcomes in women with booking HbA1c ≤ 40 mmol/mol compared with 41-49 mmol/mol in South Auckland, New Zealand.

AIMS: There are few data on pregnancy outcomes in women with pre-diabetes (HbA1c 41-49 mmol/mmol) at pregnancy booking. We aimed to (i) identify the proportion of women in Counties Manukau Health (CMH), South Auckland, New Zealand (NZ), with pre-diabetes at booking and (ii) compare outcomes between women with normal HbA1c and pre-diabetes. MATERIALS AND METHODS: Using data from a multi-ethnic population of 10,869 singleton pregnancies, booked at <20 weeks from January 2017 to December 2018 in CMH, we compared outcomes between those with normal HbA1c (≤40 mmol/mol) and those with pre-diabetes (HbA1c 41-49 mmol/mol). The primary outcomes were gestational diabetes mellitus (GDM) by NZ criteria and large for gestational age (LGA) defined as birthweight >90th customised centile. Logistic regression determined the contribution of HbA1c 41-49 mmol/mol to the development of GDM. RESULTS: Among 10,869 participants, 193 (1.78%) had an HbA1c 41-49 mmol/mol at <20 weeks' gestation. Those with HbA1c 41-49 mmol/mol were 11 times more likely to develop GDM (59.6 vs 7.9%; adjusted odds ratio (aOR) 11.16 (7.59, 16.41)) and were more likely to have an LGA baby (47 (24.4%) vs 1436 (13.5%) aOR 1.63 (1.10, 2.41)) versus those with normal HbA1c. They also had significantly higher rates of pre-eclampsia, caesarean sections, preterm births and perinatal deaths. CONCLUSIONS: Nearly two-thirds of women with a booking HbA1c of 41-49 mmol/mmol developed GDM as well as multiple other perinatal complications compared to women with HbA1c ≤40. Trials to evaluate the impact of treatment in early pregnancy on the risk of late-pregnancy complications are required.

The placenta in fetal growth restriction: What is going wrong?

The placenta is essential for the efficient delivery of nutrients and oxygen from mother to fetus to maintain normal fetal growth. Dysfunctional placental development underpins many pregnancy complications, including fetal growth restriction (FGR) a condition in which the fetus does not reach its growth potential. The FGR placenta is smaller than normal placentae throughout gestation and displays maldevelopment of both the placental villi and the fetal vasculature within these villi. Specialized epithelial cells called trophoblasts exhibit abnormal function and development in FGR placentae. This includes an altered balance between proliferation and apoptotic death, premature cellular senescence, and reduced colonisation of the maternal decidual tissue. Thus, the placenta undergoes aberrant changes at the macroscopic to cellular level in FGR, which can limit exchange capacity and downstream fetal growth. This review aims to compile stereological, in vitro, and imaging data to create a holistic overview of the FGR placenta and its pathophysiology, with a focus on the contribution of trophoblasts.

Effect of sildenafil citrate treatment in the eNOS knockout mouse model of fetal growth restriction on long-term cardiometabolic outcomes in male offspring.

Fetal growth restriction (FGR) is associated with an increased risk of hypertension, insulin resistance, obesity and cardiovascular disease in adulthood. Currently there are no effective treatments to reverse the course of FGR. This study used the eNOS knockout mouse (eNOS-/-), a model of FGR, to determine the ability of sildenafil, a potential new treatment for FGR, to improve cardiovascular and metabolic outcomes in adult offspring following a complicated pregnancy. Pregnant eNOS-/- and C57BL/6J control dams were randomised to sildenafil treatment (0.2 mg/ml in drinking water) or placebo at day 12.5 of gestation until birth. After weaning, male offspring were randomised to either a high fat (HFD; 45% kcal from fat) or normal chow diet (ND), and raised to either postnatal day 90 or 150. Growth and body composition, glucose tolerance, insulin resistance, systolic blood pressure and vascular function were analysed at both time-points. eNOS-/- offspring were significantly smaller than their C57BL/6J controls at weaning and P90 (p < 0.01); at P150 they were a similar weight. Total adipose tissue deposition at P90 was significantly increased only in eNOS-/- mice fed a HFD (p < 0.001). At P150 both C57BL/6J and eNOS-/- offspring fed a HFD demonstrated significant adipose tissue deposition (p < 0.01), regardless of maternal treatment. Both diet and maternal sildenafil treatment had a significant effect on glucose tolerance. Glucose tolerance was significantly impaired in eNOS-/- mice fed a HFD (p < 0.01); this was significant in offspring from both sildenafil and vehicle treated mothers at P90 and P150. Glucose tolerance was also impaired in C57BL/6J mice fed a HFD at both P90 and P150 (p < 0.01), but only in those also exposed to sildenafil. In these C57BL/6J mice, sildenafil was associated with impaired insulin sensitivity at P90 (p = 0.020) but increased insulin resistance at P150 (p = 0.019). Exposure to sildenafil was associated with a significant increase in systolic blood pressure in eNOS-/- mice compared with their C57BL/6J diet controls at P150 (p < 0.05). Exposure to sildenafil had differing effects on vascular function in mesenteric arteries; it increased vasodilation in response to ACh in C57BL/6J mice, but was associated with a more constrictive phenotype in eNOS-/- mice. eNOS-/- mice demonstrate a number of impaired outcomes consistent with programmed cardiometabolic disease, particularly when faced with the 'second hit' of a HFD. Exposure to sildenafil treatment during pregnancy did not increase fetal growth or significantly improve adult metabolic or cardiac outcomes. Maternal sildenafil treatment was, however, associated with small impairments in glucose handling and an increase in blood pressure. This study highlights the importance of understanding the long-term effects of treatment during pregnancy in offspring from both complicated and healthy control pregnancies.

Maternal Administration of Sildenafil Citrate Alters Fetal and Placental Growth and Fetal-Placental Vascular Resistance in the Growth-Restricted Ovine Fetus.

Intrauterine growth restriction (IUGR) causes short- and long-term morbidity. Reduced placental perfusion is an important pathogenic component of IUGR; substances that enhance vasodilation in the uterine circulation, such as sildenafil citrate (sildenafil), may improve placental blood flow and fetal growth. This study aimed to examine the effects of sildenafil in the growth-restricted ovine fetus. Ewes carrying singleton pregnancies underwent insertion of vascular catheters, and then, they were randomized to receive uterine artery embolization (IUGR) or to a control group. Ewes in the IUGR group received a daily infusion of sildenafil (IUGR+SC; n=10) or vehicle (IUGR+V; n=8) for 21 days. The control group received no treatment (n=9). Umbilical artery blood flow was measured using Doppler ultrasound and the resistive index (RI) calculated. Fetal weight, biometry, and placental weight were obtained at postmortem after treatment completion. Umbilical artery RI in IUGR+V fell less than in controls; the RI of IUGR+SC was intermediate to that of the other 2 groups (mean±SEM for control versus IUGR+V versus IUGR+SC: ∆RI, 0.09±0.03 versus -0.01±0.02 versus 0.03±0.02; F(2, 22)=4.21; P=0.03). Compared with controls, lamb and placental weights were reduced in IUGR+V but not in IUGR+SC (control versus IUGR+V versus IUGR+SC: fetal weight, 4381±247 versus 3447±235 versus 3687±129 g; F(2, 24)=5.49; P=0.01 and placental weight: 559.7±35.0 versus 376.2±32.5 versus 475.2±42.5 g; F(2, 24)=4.64; P=0.01). Sildenafil may be a useful adjunct in the management of IUGR. An increase in placental weight and fall in fetal-placental resistance suggests that changes to growth are at least partly mediated by changes to placental growth rather than alterations in placental efficiency.

Potential targets for the treatment of preeclampsia.

INTRODUCTION: Preeclampsia is a disorder of pregnancy, typically characterized by hypertension and proteinuria observed after the 20th week of gestation. Preeclampsia has dire consequences for both maternal and neonatal health: it is associated with 50,000 - 100,000 annual deaths globally, as well as serious fetal and neonatal morbidity and mortality, including increased risk of fetal growth restriction and still birth. Despite the severe health, social, and economic costs of preeclampsia, currently the only curative therapy is delivery of the baby and placenta, which itself carries the associated risks of premature birth. The lack of treatments for this condition is attributable to a number of causes, including but not limited to: a partial understanding of the complex pathophysiological mechanisms underlying this complex disease; an inability to sensitively predict women who will go on to develop the disease; and a paucity of robust animal models with which to test new treatments. AREAS COVERED: Recently, progress has been made in identifying potential new therapeutic targets. This review will discuss in detail the evidence supporting further investigation of these targets, which include angiogenic factors, agents that increase vasodilation, anti-inflammatory drugs, substances that reduce oxidative stress, and statins. EXPERT OPINION: New therapeutic targets have the potential to make a significant positive impact on maternal and neonatal health. It is exciting that a number of potential therapies are currently being investigated; however, it is also vital that basic research continues to identify potential mechanisms and targets, and that any potential therapy is thoroughly tested before progression to clinical trial.