Women's experience of perinatal support in a high migrant Australian population during the COVID-19 pandemic: a mixed methods study.

BACKGROUND: As a COVID-19 risk mitigation measure, Australia closed its international borders for two years with significant socioeconomic disruption including impacting approximately 30% of the Australian population who are migrants. Migrant populations during the peripartum often rely on overseas relatives visiting for social support. High quality social support is known to lead to improved health outcomes with disruption to support a recognised health risk. AIM: To explore women's experience of peripartum social support during the COVID-19 pandemic in a high migrant population. To quantify type and frequency of support to identify characteristics of vulnerable perinatal populations for future pandemic preparedness. METHODS: A mixed methods study with semi-structured interviews and a quantitative survey was conducted from October 2020 to April 2021. A thematic approach was used for analysis. RESULTS: There were 24 participants interviewed both antenatally and postnatally (22 antenatal; 18 postnatal). Fourteen women were migrants and 10 Australian born. Main themes included; 'Significant disruption and loss of peripartum support during the COVID-19 pandemic and ongoing impact for migrant women'; 'Husbands/partners filling the support gap' and 'Holding on by a virtual thread'. Half of the participants felt unsupported antenatally. For Australian born women, this dissipated postnatally, but migrants continued to feel unsupported. Migrant women discussed partners stepped into traditional roles and duties of absent mothers and mothers-in-law who were only available virtually. CONCLUSION: This study identified disrupted social support for migrant women during the pandemic, providing further evidence that the pandemic has disproportionately impacted migrant populations. However, the benefits identified in this study included high use of virtual support, which could be leveraged for improving clinical care in the present and in future pandemics. The COVID-19 pandemic impacted most women's peripartum social support with migrant families having ongoing disruption. Gains in the pandemic included greater gender equity for domestic work as husbands/partners increased their contribution to domestic work and childcare.

Previous High-Intensity Breastfeeding Lowers the Risk of an Abnormal Fasting Glucose in a Subsequent Pregnancy Oral Glucose Tolerance Test.

Breastfeeding is associated with reduced lifetime cardiometabolic risk, but little is known regarding the metabolic benefit in a subsequent pregnancy. The primary aim of this study was to investigate the association between breastfeeding duration and intensity and next pregnancy oral glucose tolerance test (OGTT) results. A retrospective cohort study was conducted from March 2020 to October 2022. All multiparous women who met inclusion criteria and gave birth during the study period were eligible for inclusion. Analysis was stratified by risk for gestational diabetes (GDM). High GDM risk criteria included previous GDM and BMI > 35 kg/m2. The association between breastfeeding duration and high-intensity breastfeeding (HIBF) and subsequent pregnancy OGTT were assessed with multivariate logistic models adjusted for statistically and clinically relevant covariables. There were 5374 multiparous participants who met the inclusion criteria for analysis. Of these, 61.7% had previously breastfed for >6 months, and 43.4% were at high risk for GDM. HIBF was associated with 47% reduced odds of an abnormal fasting glucose in a subsequent pregnancy OGTT (aOR 0.53; 95%CI 0.38-0.75; p < 0.01). There was no association between HIBF and other glucose results on the OGTT. Women who smoked were least likely to breastfeed at high intensity (aOR 0.31; 95%CI 0.21-0.47; p < 0.01). South Asian women had 65% higher odds of HIBF than women who identified as White/European (aOR 1.65; 1.36-2.00; p < 0.01). This study highlights the importance of exclusive breastfeeding to potentially reduce the prevalence of GDM and may also translate into long-term reduction of cardiometabolic risk.

Changing indications and antenatal prognostic factors for ex-utero intrapartum treatment procedures.

OBJECTIVE: In cases of suspected neonatal airway obstruction, the ex-utero intrapartum treatment (EXIT) procedure is used to secure the airway while a fetus remains on placental circulation. We report indications and outcomes from all EXIT procedures at a tertiary obstetric unit between 1997 and 2020. METHOD: Retrospective cohort study with data collected from maternal and neonatal medical records. RESULTS: Indications for EXIT procedures were micrognathia (n = 7), lymphatic malformations (n = 5), cervical teratomas (n = 4), goiters (n = 2), and intra-oral epulis (n = 1). Infants with a fetal teratoma were delivered earliest due to 75% presenting with preterm premature rupture of membranes or preterm labor. Low birth weight was found in 75% of these neonates; they did not survive 1 year. Intubation at EXIT occurred for 58% (n = 11) of babies, and six neonates required a tracheostomy. In four cases of fetal micrognathia, the inferior facial angle (IFA) was noted to be <5th centile. All but one micrognathia case had polyhydramnios. Of the total cohort, 75% of neonates were alive at 1 year. CONCLUSION: Risks for neonatal demise with EXIT include fetal teratoma, low birth weight, and prematurity. Micrognathia has become an increasingly valid indication for the procedure. The combination of polyhydramnios and IFA <5% correlates well with severe airway obstruction and suggests consideration of EXIT.

Investigating service delivery and perinatal outcomes during the low prevalence first year of COVID-19 in a multiethnic Australian population: a cohort study.

OBJECTIVE: Investigate the impact of the COVID-19 pandemic on perinatal outcomes in an Australian high migrant and low COVID-19 prevalent population to identify if COVID-19 driven health service changes and societal influences impact obstetric and perinatal outcomes. DESIGN: Retrospective cohort study with pre COVID-19 period 1 January 2018-31 January 2020, and first year of global COVID-19 period 1 February 2020-31 January 2021. Multivariate logistic regression analysis was conducted adjusting for confounders including age, area-level socioeconomic status, gestation, parity, ethnicity and body mass index. SETTING: Obstetric population attending three public hospitals including a major tertiary referral centre in Western Sydney, Australia. PARTICIPANTS: Women who delivered with singleton pregnancies over 20 weeks gestation. Ethnically diverse women, 66% overseas born. There were 34 103 births in the district that met inclusion criteria: before COVID-19 n=23 722, during COVID-19 n=10 381. MAIN OUTCOME MEASURES: Induction of labour, caesarean section delivery, iatrogenic and spontaneous preterm birth, small for gestational age (SGA), composite neonatal adverse outcome and full breastfeeding at hospital discharge. RESULTS: During the first year of COVID-19, there was no change for induction of labour (adjusted OR, aOR 0.97; 95% CI 0.92 to 1.02, p=0.26) and a 25% increase in caesarean section births (aOR 1.25; 95% CI 1.19 to 1.32, p<0.001). During the COVID-19 period, we found no change in iatrogenic preterm births (aOR 0.94; 95% CI 0.80 to 1.09) but a 15% reduction in spontaneous preterm birth (aOR 0.85; 95% CI 0.75 to 0.97, p=0.02) and a 10% reduction in SGA infants at birth (aOR 0.90; 95% CI 0.82 to 0.99, p=0.02). Composite adverse neonatal outcomes were marginally higher (aOR 1.08; 95% CI 1.00 to 1.15, p=0.04) and full breastfeeding rates at hospital discharge reduced by 15% (aOR 0.85; 95% CI 0.80 to 0.90, p<0.001). CONCLUSION: Despite a low prevalence of COVID-19, both positive and adverse obstetric outcomes were observed that may be related to changes in service delivery and interaction with healthcare providers. Further research is suggested to understand the drivers for these changes.

Outcomes and success of new tiered perinatal transfer policy within a tertiary level obstetric unit in Australia.

BACKGROUND: New South Wales Health introduced the new Tiered Networking Arrangements for Perinatal Care in New South Wales policy directive (TPN Policy), which defined key performance and quality indicators after implementation. AIMS: This study aims to assess the success of the TPN Policy implementation in the Western Sydney TPN in accordance with key performance indicators. MATERIALS AND METHODS: This is a retrospective cohort study of acute perinatal transfers within the Western Sydney TPN between 1 December 2019 to 31 December 2020. The primary outcome is compliance with objectives of the TPN Policy, as measured as an Aggregate Compliance Score comprising the five measures. Secondary outcomes include clinical, neonatal and logistics outcomes. RESULTS: There were 181 acute perinatal transfers within, into or out of the Western Sydney TPN between 1 December 2019 to 31 December 2020. There were 122 transfers within the network, 40 into the TPN and 19 were out of the TPN. All groups were at least partially compliant with the TPN Policy. No transfers in any of groups scored below three ('partially compliant'). A quarter of transfers gave birth within 24 h of transfer. Over half of those who were transferred and admitted went on to give birth prior to discharge or transfer. CONCLUSIONS: Overall, the TPN Policy met its objectives after implementation in the Western Sydney TPN, while maintaining appropriate neonatal outcomes. All women arrived at an appropriate facility prior to giving birth, although the majority did not give birth within 24 h. Neonatal intensive care unit bed availability is a key limitation to future improvement.

The BLIiNG study - Breastfeeding length and intensity in gestational diabetes and metabolic effects in a subsequent pregnancy: A cohort study.

BACKGROUND: Gestational diabetes mellitus is associated with higher risk for developing type 2 diabetes. Breastfeeding is protective against the development of type 2 diabetes after gestational diabetes. There are no data regarding the effect of breastfeeding on the development of recurrent gestational diabetes. OBJECTIVE: Investigate the relationship of previous breastfeeding duration and intensity with the recurrence of gestational diabetes, and second pregnancy glucose tolerance test results. METHODS: We conducted a questionnaire-based pilot cohort study, enrolling 210 women during a subsequent second pregnancy, after a gestational diabetes-affected first pregnancy. Models for length and intensity of breastfeeding as predictors of the oral glucose tolerance test and for diagnosis of gestational diabetes in second pregnancy were fitted and then adjusted for possible confounders. RESULTS: Recurrent gestational diabetes rate in the study cohort was 70% (n = 146). In a fully adjusted model high intensity breastfeeding was associated with a lower 2-hour glucose level on the oral glucose tolerance test (by 0.66 mmol/L, 95% CI [0.15-1.17]; p = 0.01) and breastfeeding greater than six months with a lower 1-hour glucose on the oral glucose tolerance test (by 0.67 mmol/L, 95% CI [0.16-1.19]; p = 0.01), compared to women who breastfed less intensively or for a shorter duration respectively. There was an 18% reduction in the risk of gestational diabetes if a woman breastfed for more than six months (RR 0.82, 95% CI [0.69-0.98]; p = 0.03). The association was attenuated in the fully adjusted model (RR 0.89, 95% CI [0.78-1.02]; p = 0.09). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: We found the risk of recurrent gestational diabetes was reduced by both increased duration and intensity of breastfeeding. Antenatal lactation education should be embedded into care pathways for women diagnosed with gestational diabetes.

Exploring the COVID-19 pandemic experience of maternity clinicians in a high migrant population and low COVID-19 prevalence country: A qualitative study.

BACKGROUND: Australia experienced a low prevalence of COVID-19 in 2020 compared to many other countries. However, maternity care has been impacted with hospital policy driven changes in practice. Little qualitative research has investigated maternity clinicians' perception of the impact of COVID-19 in a high-migrant population. AIM: To investigate maternity clinicians' perceptions of patient experience, service delivery and personal experience in a high-migrant population. METHODS: We conducted semi-structured in-depth interviews with 14 maternity care clinicians in Sydney, New South Wales, Australia. Interviews were conducted from November to December 2020. A reflexive thematic approach was used for data analysis. FINDINGS: A key theme in the data was 'COVID-19 related travel restrictions result in loss of valued family support for migrant families'. However, partners were often 'stepping-up' into the role of missing overseas relatives. The main theme in clinical care was a shift in healthcare delivery away from optimising patient care to a focus on preservation and safety of health staff. DISCUSSION: Clinicians were of the view migrant women were deeply affected by the loss of traditional support. However, the benefit may be the potential for greater gender equity and bonding opportunities for partners. Conflict with professional beneficence principles and values may result in bending rules when a disconnect exists between relaxed community health orders and restrictive hospital protocols during different phases of a pandemic. CONCLUSION: This research adds to the literature that migrant women require individualised culturally safe care because of the ongoing impact of loss of support during the COVID-19 pandemic.

Aspirin for the prevention of pre-eclampsia in women with pre-existing diabetes: Systematic review.

BACKGROUND: There is a lack of evidence for pre-eclampsia prophylaxis with aspirin in women with pre-existing diabetes mellitus (DM). AIMS: To examine the evidence for aspirin in pre-eclampsia prophylaxis in women with pre-existing DM. MATERIAL AND METHODS: An electronic search using Ovid MEDLINE, Embase, CinicalTrials.gov and the Cochrane CENTRAL register of controlled trials through to February 2021 was performed. Reference lists of identified studies, previous review articles, clinical practice guidelines and government reports were manually searched. Randomised controlled trials (RCTs) of aspirin vs placebo for pre-eclampsia prophylaxis were included. Articles were manually reviewed to determine if cohorts included women with DM. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data from included trials were extracted independently by two authors who also independently assessed risk of bias as per the Cochrane Handbook criteria version 5.1.0. Data were analysed using Rev-Man 5.4. RESULTS: Forty RCTs were identified, of which 11 included a confirmed subset of women with DM; however, data were insufficient for meta-analysis. Meta-analysis of 930 women with DM, from individual patient data included in a systematic review and unpublished data from one of the 11 RCTs, showed a non-significant difference in the outcome of pre-eclampsia in participants treated with aspirin compared to placebo (odds ratio 0.58; 95% CI 0.20-1.71; P = 0.33). CONCLUSIONS: Pre-eclampsia risk reduction with aspirin prophylaxis in women with pre-existing DM may be similar to women without pre-existing DM. However, randomised data within this meta-analysis were insufficient, warranting the need for further studies within this high-risk group of women.

Perinatal and Child Factors Mediate the Association between Preeclampsia and Offspring School Performance.

OBJECTIVE: To determine whether maternal preeclampsia is an independent risk factor for poorer academic school performance in offspring, taking into account important perinatal and child factors. STUDY DESIGN: A population-based cohort study using record-linkage of state-wide data was undertaken. We evaluated children born at 28+ weeks of gestation in New South Wales, Australia who had grade 3 record-linked education outcomes via the National Assessment Program-Literacy and Numeracy (NAPLAN) between 2009 and 2014. Children with in utero preeclampsia exposure were compared with those without exposure. Robust multivariable Poisson models were used to determine adjusted relative risks. RESULTS: Crude models demonstrated an increased risk of scoring below the national minimal standard in all 5 domains (reading, writing, spelling, grammar and punctuation, and numeracy) for children exposed to preeclampsia, ranging from a relative risk (RR) of 1.13 (95% CI, 1.04-1.24) for reading to 1.19 (95% CI, 1.09-1.30) for numeracy. These differences were attenuated once adjusted for perinatal and child factors (RR, 1.07 [95% CI, 0.97-1.18] to 1.11 (95% CI, 0.99-1.22]), with combined perinatal and childhood factors mediating between 35.7% (writing) to 55.1% (spelling) of the association. Gestational age at birth was the most important perinatal factor, explaining 10.5% (grammar and punctuation) to 20.6% (writing) of the association between preeclampsia and poor school performance, followed by small for gestational age. CONCLUSION: The poorer educational performance experienced by children born to women with preeclampsia appears largely attributable to perinatal and childhood factors, suggesting an opportunity to improve school performance in children exposed to preeclampsia by optimizing these perinatal factors, particularly gestational age at birth.

Association of Preeclampsia With Myocardial Injury Among Patients Undergoing Noncardiac Surgery: The PREECLAMPSIA-VISION Study.

BACKGROUND: In women, preeclampsia has a known association with increased long-term cardiovascular morbidity and mortality. However, it is unknown whether it is associated with increased postoperative cardiovascular morbidity and mortality in women. We aimed to determine if preeclampsia is an independent risk factor for myocardial injury after noncardiac surgery (MINS) and postoperative 30-day mortality. METHODS: This study was a large international multicentre cohort study of a representative sample of 40,004 patients recruited from August 2007 to November 2013. Participants were ≥ 45 years of age and underwent inpatient noncardiac surgery. Within this cohort, our study examined women with a history of pregnancy. Using multivariable models, we explored the association between a history of pregnancy affected by preeclampsia and our primary outcome of MINS and secondary outcome of postoperative mortality within 30 days. MINS was defined as prognostically relevant myocardial injury due to ischemia that occurred during or within 30 days after noncardiac surgery. RESULTS: Analyses were restricted to the 13,902 participants with a history of pregnancy. Among these women, 976 (7.0%) had a history of preeclampsia. A history of preeclampsia was associated with an increased risk of MINS, with an adjusted hazard ratio of 1.26 (95% confidence interval 1.03-1.53; P = 0.02). Preeclampsia was not significantly associated with 30-day mortality. CONCLUSIONS: Preeclampsia is a risk factor for MINS and should be considered in the preoperative cardiovascular risk assessment of women.

Selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitors and epidemiological characteristics associated with prenatal diagnosis of congenital heart disease.

OBJECTIVE: Identify early pregnancy associations of congenital heart disease (CHD) in a multiethnic cohort. METHODS: This retrospective observational cohort study compared the general obstetric population to women who gave birth at a referral centre in Australia between 2012 and 2017, after 20 weeks' of gestation, with a pregnancy affected by CHD. We defined mood disorder and anxiety as a history of self-reported or medically diagnosed anxiety, depression, postpartum depression or bipolar disorder. RESULTS: We compared epidemiological factors between 30 842 general obstetric patients and 470 obstetric patients with a foetus affected by CHD. Multivariate analysis showed independent associations between CHD and use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in the first trimester (relative risk [RR] 4.14, 95% CI 2.58-6.65), history of anxiety or mood disorder with no SSRI/SNRI first trimester (RR 2.20, 95% CI 1.77-2.74), folate and/or pregnancy multivitamin use in the first trimester (RR 0.69, 95% CI 0.55-0.87) and increased risk with maternal age >40 years (RR 2.30, 95% CI 1.57-3.38). CONCLUSIONS: Our data show maternal mood disorders with and without SSRI or SNRI use, maternal age >40 years and lack of multivitamin/folate use to be independently associated with CHD in pregnancy.

Pregnancy complicated by refractory severe hypercholanaemia from sodium taurocholate co-transporting polypeptide deficiency.

Sodium taurocholate co-transporting polypeptide deficiency is a rare metabolic autosomal recessive condition resulting in critically elevated plasma bile acid levels. Hypercholanaemia in similar conditions such as intrahepatic cholestasis of pregnancy has been associated with an increased risk of adverse obstetric outcomes including stillbirth. We present the first case of Sodium taurocholate co-transporting polypeptide deficiency in a current pregnancy in a patient with one previous stillbirth in the context of severe hypercholanaemia, where conventional treatments for cholestasis including ursodeoxycholic acid, rifampicin and cholestyramine were ineffective. Therapeutic plasma exchange and novel treatment with elobixibat were trialed with mixed results. The pregnancy resulted in an iatrogenic preterm delivery of a live infant at 32 weeks gestation.

Fetal adrenal gland: Total gland volume and fetal zone to total gland ratio as markers of small for gestational age.

PURPOSE: Fetal adrenal gland changes have previously been investigated as novel markers of preterm labor and small for gestational age (SGA) fetuses. We aimed to compare the fetal adrenal gland parameters in SGA and appropriate for gestational age (AGA) fetuses. METHODS: A prospective cohort study was conducted on SGA fetuses with estimated fetal weight (EFW) ≤10th centile and AGA (EFW >10th centile) at 17 to 34 weeks gestation. Fetal adrenal total gland volume (TGV), TGV corrected for EFW (cTGV), fetal zone volume (FZV), FZV corrected for EFW (cFZV), and FZV:TGV ratio were compared and correlated with gestational age and EFW. Receiver operator curves assessed FZV:TGV ratio, cTGV, and cFZV in detecting SGA. RESULTS: Ultrasound examinations from 103 AGA and 50 SGA fetuses showed that (a) SGA fetuses had higher TGV (P = .002), FZV (P = .001), and FZV:TGV (P = .036) compared to AGA fetuses; (b) fetal adrenal TGV, FZV, cFZV, and FZV:TGV increase with advancing gestational age and EFW while cTGV does not; (c) Fetal adrenal changes in cTGV, cFZV, and FZV:TGV have ability to differentiate SGA; (d) FZV:TGV ratio 10 and 25 may be used to identify or exclude SGA in antenatally suspected SGA. CONCLUSIONS: We investigated the concept that SGA fetuses have measurable changes to the adrenal gland. We have shown that fetal TGV, TGV, and FZV:TGV ratio show differences between AGA and SGA with TGV remaining significant after accounting for GA at scan. These findings may be useful as potential biomarkers for diagnosing or excluding SGA.

Therapeutic plasma exchange for the management of severe gestational hypertriglyceridaemic pancreatitis due to lipoprotein lipase mutation.

SUMMARY: A 19-year-old female presented at 25-weeks gestation with pancreatitis. She was found to have significant hypertriglyceridaemia in context of an unconfirmed history of familial hypertriglyceridaemia. This was initially managed with fasting and insulin infusion and she was commenced on conventional interventions to lower triglycerides, including a fat-restricted diet, heparin, marine oil and gemfibrozil. Despite these measures, the triglyceride levels continued to increase as she progressed through the pregnancy, and it was postulated that she had an underlying lipoprotein lipase defect. Therefore, a multidisciplinary decision was made to commence therapeutic plasma exchange to prevent further episodes of pancreatitis. She underwent a total of 13 sessions of plasma exchange, and labour was induced at 37-weeks gestation in which a healthy female infant was delivered. There was a rapid and significant reduction in triglycerides in the 48 h post-delivery. Subsequent genetic testing of hypertriglyceridaemia genes revealed a missense mutation of the LPL gene. Fenofibrate and rosuvastatin was commenced to manage her hypertriglyceridaemia postpartum and the importance of preconception counselling for future pregnancies was discussed. Hormonal changes in pregnancy lead to an overall increase in plasma lipids to ensure adequate nutrient delivery to the fetus. These physiological changes become problematic, where a genetic abnormality in lipid metabolism exists and severe complications such as pancreatitis can arise. Available therapies for gestational hypertriglyceridaemia rely on augmentation of LPL activity. Where there is an underlying LPL defect, these therapies are ineffective and removal of triglyceride-rich lipoproteins via plasma exchange should be considered. LEARNING POINTS: Hormonal changes in pregnancy, mediated by progesterone,oestrogen and human placental lactogen, lead to a two- to three-fold increase in serum triglyceride levels. Pharmacological intervention for management of gestational hypertriglyceridaemia rely on the augmentation of lipoprotein lipase (LPL) activity to enhance catabolism of triglyceride-rich lipoproteins. Genetic mutations affecting the LPL gene can lead to severe hypertriglyceridaemia. Therapeutic plasma exchange (TPE) is an effective intervention for the management of severe gestational hypertriglyceridaemia and should be considered in cases where there is an underlying LPL defect. Preconception counselling and discussion regarding contraception is of paramount importance in women with familial hypertriglyceridaemia.

Lipid profiling in maternal and fetal circulations in preeclampsia and fetal growth restriction-a prospective case control observational study.

BACKGROUND: While many risk factors for preeclampsia, such as increased body mass index, advanced maternal age, chronic hypertension, diabetes, are now established in clinical practice, maternal lipid profile has not been included in the risk assessment for preeclampsia. We aim to characterize the serum levels of Total Cholesterol (TC), High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglycerides (TG), Apolipoprotein A1, Apolipoprotein B and their ratios TC/HDL and ApoB/ApoA1 in the maternal and fetal circulations of normal pregnancy, preeclampsia (PE), fetal growth restriction (FGR) and PE + FGR. METHODS: A prospective cross-sectional case control study was conducted measuring maternal and fetal lipid levels by enzymatic analysis and immune-turbidimetric enzymatic assays. FGR was defined by elevated umbilical artery Doppler resistance in association with estimated fetal weight < 10%. Kruskal Wallis non-parametric analysis of variance was used to test for homogeneity across the clinical groups for each of the variables, Mann-Whitney tests for pairwise comparisons and Spearman rank correlation were used to quantify gestational age-related changes. RESULTS: (1) TG levels were elevated in maternal PE and cord blood PE + FGR groups compared to normal pregnancies. (2) A statistically significant elevation of fetal ApoB levels was observed in PE, FGR and PE + FGR compared to normal pregnancies. Apolipoprotein levels A1 and B were not different between maternal groups. (3) TC, HDL, LDL and TC/HDL levels did not show any significant gestational variation or between clinical groups in the maternal or fetal circulation. CONCLUSIONS: Elevation in maternal TG levels may have a role in the pathogenesis of PE. The implications of elevated maternal and fetal TG levels and elevated fetal Apolipoprotein B levels deserves further exploration of their role in long term cardiovascular risk in the mother as well as the offspring.

Urinary and Serum Angiogenic Markers in Women With Preexisting Diabetes During Pregnancy and Their Role in Preeclampsia Prediction.

OBJECTIVE: To determine the correlation between urinary and serum placental growth factor (PlGF) and investigate the predictive value as pregnancy progresses of urinary PlGF compared with serum PlGF, soluble fms-like tyrosine kinase 1 (sFLT-1), and the sFLT-1-to-PlGF ratio for the outcome of preeclampsia in women with preexisting diabetes. RESEARCH DESIGN AND METHODS: A multicenter prospective cohort study was conducted of 158 women with preexisting insulin-requiring diabetes (41 with type 1 and 117 with type 2). Urinary PlGF and serum PlGF, sFLT-1, and the sFLT-1-to-PlGF ratio were assessed four times (14, 24, 30, and 36 weeks' gestation), and the association with the outcome of preeclampsia was investigated. RESULTS: A correlation between urinary and serum PlGF was demonstrated from 24 weeks' gestation onward (P < 0.001). At all time points, those who developed preeclampsia had lower serum PlGF levels (P < 0.05), and receiver operating characteristic curves demonstrated that serum PlGF in this cohort performed better than the serum sFLT-1-to-PlGF ratio as a predictive test for preeclampsia. Preconception HbA1c ≥6.5% (48 mmol/mol) was an important discriminative predictor for preeclampsia (P = 0.01). CONCLUSIONS: This study prospectively describes the longitudinal changes in urinary PlGF alongside serum angiogenic markers throughout pregnancy in women with preexisting diabetes. We demonstrate correlation between urinary and serum PlGF and that in women with preexisting diabetes in pregnancy, serum PlGF is a better predictor of preeclampsia than the sFLT-1-to-PlGF ratio.

Urinary placental growth factor in preeclampsia and fetal growth restriction: An alternative to circulating biomarkers?

AIM: To correlate plasma and urinary soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) in preeclampsia (PE) and fetal growth restriction (FGR) and assess the performance in detecting established disease. METHODS: A cross-sectional case-control study recruited 26-40 weeks gestation pregnancies into four clinical groups: normal pregnancy, PE, PE + FGR, and FGR. enzyme-linked immunosorbent assay (ELISA) measurements of urinary and plasma sFlt-1 and PlGF levels were performed. Urinary levels of sFlt-1 and PIGF were normalized to creatinine. Spearman's rank correlation was used to assess the association between plasma and urinary levels of sFlt-1 and PIGF, and receiver operating characteristic graphs were used to quantify the performance of each individual marker and their ratios in predicting normal versus pathological pregnancies affected by preeclampsia and/or FGR. RESULTS: There was a significant correlation between plasma PlGF and urinary PlGF (r = 0.718, P < 0.001) in all groups. In the pathological groups, plasma sFlt-1 and urinary sFlt-1 as well as plasma sFlt-1: PIGF ratio and urinary sFlt-1: PlGF ratio were higher, but plasma PIGF and urinary PlGF were lower when compared to normal pregnancy. Plasma PIGF and plasma sFlt-1: PlGF ratio was comparable in performance to urinary PlGF and urinary sFlt-1: PIGF ratio for the diagnosis of preeclampsia and/or FGR. CONCLUSION: Urinary PIGF can be used as an alternative to circulating biomarkers in preeclampsia and FGR. Plasma sFlt-1, PlGF and sFlt-1: PlGF ratio as well as urinary PIGF and sFlt-1: PlGF ratio can be used to differentiate between normal pregnancy and pregnancies complicated by preeclampsia and FGR.

Characterization of fetal monocytes in preeclampsia and fetal growth restriction.

Background There is little available data on fetal monocyte phenotype and function. A prospective cross-sectional pilot study was conducted to describe the cord blood monocyte subset phenotype in preeclampsia (PE) and fetal growth restriction (FGR) as compared to normal pregnancy and maternal circulation. Methods Maternal and cord blood samples from 27 pregnancies were collected at delivery from normal pregnancy, PE, FGR and PE+FGR. The distribution of fetal monocyte subtypes was characterized by CD14 and CD16 expression using flow cytometry and compared for each clinical group using a classification of classical, intermediate and non-classical subsets. Results The intermediate monocytes were the dominant monocyte subset in the cord blood of PE and PE+FGR with an increase in the combined inflammatory monocyte subsets intermediate and non-classical in PE compared to normal pregnancy. The non-classical monocyte subset proportion was elevated in all pathological groups PE, FGR and PE+FGR. A significant reduction in the non-classical monocyte subset was observed in the cord blood of the normal pregnancy group as compared to the maternal circulation. Conclusion This study describes for the first time in the fetal circulation, dominant monocyte intermediate subsets and increased inflammatory subsets in PE as well as increased non-classical subsets in PE and FGR compared to normal pregnancy.

Antenatal ultrasound diagnosis of small bowel non-rotation in complex left isomerism: a case report.

PRESENTATION OF CASE: A multiparous expectant mother was referred to our tertiary unit at 23 weeks with a complex fetal cardiac anomaly in the context of suspected heterotaxy syndrome. The cardiac findings were consistent with isomerism: the fetal cardiac position was levocardia with a single functioning double outlet ventricle and AV valve, pulmonary stenosis, and interrupted inferior vena cava (IVC) with azygous continuation. The fetal abdominal situs was also altered, with the stomach to the right, and the hepatobiliary system midline to left. The spleen was not identified antenatally or postnatally. At 36 weeks, ultrasound revealed an abnormal bowel pattern with small bowel loops on the right side of the abdomen and large bowel on the left, suggesting a diagnosis of non- rotation. The infant was delivered vaginally at 39 weeks. The cardiac diagnosis and non-rotation of the small bowel were confirmed by postnatal echocardiography and contrast fluoroscopy. DISCUSSION: Heterotaxy syndrome is traditionally classified into right or left isomerism depending on how and where the organs are anatomically arranged. The case presented here demonstrates mixed laterality and prenatal ultrasound features of non-rotation. CONCLUSION: It is important to be informed of the embryological variants of isomerism and actively seek antenatal evidence of bowel non-rotation in such cases.

Microalbuminuria as an early predictor of preeclampsia in the pre-gestational diabetic population: A prospective cohort study.

OBJECTIVES: To determine if microalbuminuria can be used as a predictive marker of preeclampsia and adverse pregnancy and neonatal outcomes in women with pre-existing diabetes and to compare the prognostic utility of urinary albumin to creatinine ratio (uACR) and urinary protein to creatinine ratio (uPCR). STUDY DESIGN: Multicentre prospective cohort study. Antenatal Diabetes in Pregnancy clinics at three tertiary referral hospitals in Western Sydney, Australia. 158 women with pre-existing diabetes requiring insulin in pregnancy. A spot uPCR and uACR was performed in each trimester. Pregnancy and fetal outcomes were investigated using linear models and receiver-operating characteristic (ROC) curves. MAIN OUTCOME MEASURES: The primary outcome was preeclampsia (PE). Secondary outcomes investigated were other adverse pregnancy and neonatal outcomes. RESULTS: Increased levels of both uPCR and uACR in trimester 3 were associated with the occurrence of PE (p = 0.007, 0.010 respectively). In the 113 patients with normal pregnancy uPCR (<30 mg/mmol) in trimester 1, microalbuminuria was found to be predictive of PE (p = 0.01) and need for operative delivery (p = 0.03). CONCLUSIONS: In women with pre-existing diabetes, uPCR and uACR appear to have similar ability to diagnose PE, but microalbuminuria demonstrates prognostic ability at a much earlier gestation, prior to the onset of other signs or symptoms of PE. We therefore suggest that assessing microalbuminuria rather than overt proteinuria in trimester 1 provides prognostic information in women with pre-existing diabetes requiring insulin and should be used routinely to evaluate risk of PE in this high-risk cohort of women.