Impact of preconception weight loss on fasting glucose and pregnancy outcomes in women with obesity: A randomized trial.

OBJECTIVE: This study examined the effectiveness of a nonsurgical, preconception weight loss intervention on pregnancy outcomes in women with obesity. METHODS: This was a two-arm, parallel-group randomized controlled trial. A total of 164 women with BMI 30 to 55 kg/m2 who were aged 18 to 38 years and planning pregnancy were randomized to a 12-week standard dietary intervention (SDI; n = 79) or a modified very low-energy diet (VLED; n = 85). Participants were observed for ≤48 weeks while trying for pregnancy and then during pregnancy. The primary outcome was maternal fasting plasma glucose at 26 to 28 weeks' gestation. Exploratory outcomes were individual and composite obesity-related adverse pregnancy outcomes. RESULTS: Weight loss was greater in the VLED group (SDI 3.2 [0.6] kg vs. VLED 13.0 [0.5] kg, p < 0.01). In completers who had a singleton live birth (SDI 22/79 vs. VLED 35/85, p = 0.10), there was no difference in fasting glucose at 26 to 28 weeks' gestation (SDI 4.8[0.2] mmol/L vs. VLED 4.6 [0.1] mmol/L, p = 0.42). However, the composite of adverse pregnancy outcomes was significantly lower in the VLED group (p < 0.001). CONCLUSIONS: Substantial prepregnancy weight loss in women with obesity does not alter fasting glucose at 26 to 28 weeks' gestation but does reduce a composite of adverse pregnancy outcomes. A better understanding of metabolic changes in pregnancy after preconception weight loss may assist in improving maternal and neonatal health outcomes.

Time to pregnancy after a prepregnancy very-low-energy diet program in women with obesity: substudy of a randomized controlled trial.

OBJECTIVE: To examine the impact of a prepregnancy very-low-energy diet (VLED) program on time to pregnancy in women with obesity. DESIGN: Substudy of a two-arm parallel group randomized controlled trial. SETTING: Multiple tertiary care centers. PATIENT(S): Women 18-38 years old with obesity (body mass index 30-55 kg/m2) and planning conception. INTERVENTION(S): One hundred sixty-four normoglycemic women with body mass index 30-55 kg/m2, aged 18-38 years, and planning pregnancy were recruited through a social media platform for a two-arm randomized controlled trial. Women were allocated to a 12-week standard dietary intervention (SDI) or modified VLED. Completers of the intervention were observed for up to 48 weeks, and time to pregnancy was recorded. MAIN OUTCOME MEASURE(S): The prespecified exploratory outcome for this substudy was time to pregnancy between the completion of the 12-week intervention and the date of conception. RESULT(S): Maternal weight loss at the end of the 12-week intervention was 3.1% in the SDI group and 11.9% in the VLED group. In completers of the 12-week intervention, time to pregnancy was significantly shorter in the women allocated to the VLED group than in the SDI group. Post hoc analysis showed that this difference in time to conception was particularly overt within 90 days of the intervention. CONCLUSION(S): A VLED program that achieves substantial weight loss before conception reduces time to pregnancy compared with an SDI in women with obesity. TRIAL REGISTRATION NUMBER: ACTRN12614001160628.

INTERGROWTH-21st compared with GROW customized centiles in the detection of adverse perinatal outcomes at term.

Background: INTERGROWTH-21st charts provide standards for infants born under optimal pregnancy conditions. However, their validity in a general obstetric population is unclear. We aimed to identify whether INTERGROWTH-21st charts, compared with gestation related optimal weight (GROW) charts customized on maternal height, weight, and parity, better identified the at-risk infant.Methods: We performed a retrospective cohort analysis of all term women who gave birth at a single tertiary obstetric center during the period 1994-2016. Routinely collected maternity data was used for analysis. The primary outcome was an Apgar score <7 at 5 min. Secondary outcomes included Apgar score <5 at 5 min, stillbirth or admission to the neonatal intensive care unit (NICU). Populations of newborns were identified as SGA by: (a) INTERGROWTH-21st <10th centile (SGAIG10th); (b) INTERGROWTH-21st z-score < -1 (SGAIGzscore); and (c) GROW customized charts <10th (SGAcust). The subgroups identified by only one chart were also specifically examined. Each SGA group was compared to infants appropriate for gestational age (AGA) on all charts (non-SGA).Results: Data for 71,487 births were available for analysis after exclusion of women with missing height or weight data. Only 3280 (4.6%) newborns were considered SGAIG10th, with 5878 (8.2%) SGAIGzscore and 7599 (10.6%) SGAcust. INTERGROWTH-21st identified only 110 additional infants (0.15%) that were not identified by customized charts; none of these experienced any adverse outcomes. Customized centiles identified a further 4429 (6.2%) SGA infants (SGAcust-only) that were not identified as SGAIG10th, and who did demonstrate an increased risk of Apgar score <7 (OR 1.33, 95%CI 1.08-3.28) and stillbirth (OR 2.47, 95%CI 1.41-4.44) compared to the non-SGA infant. Significantly more obese women had infants considered SGAcust (19.3%) than SGAIG10th (10.0%) or SGAIGzscore (9.9%).Conclusions: Amongst our general obstetric study population, the 10th centile of INTERGROWTH-21st identified only 4.6% of infants as SGA and was less likely to identify infants of obese women as SGA. Customized centiles identified almost all SGA-IG infants, including an additional group (SGAcust-only) at higher risk of stillbirth and adverse outcomes compared with non-SGA infants.

Identification of the optimal growth charts for use in a preterm population: An Australian state-wide retrospective cohort study.

BACKGROUND: Preterm infants are a group at high risk of having experienced placental insufficiency. It is unclear which growth charts perform best in identifying infants at increased risk of stillbirth and other adverse perinatal outcomes. We compared 2 birthweight charts (population centiles and INTERGROWTH-21st birthweight centiles) and 3 fetal growth charts (INTERGROWTH-21st fetal growth charts, World Health Organization fetal growth charts, and Gestation Related Optimal Weight [GROW] customised growth charts) to identify which chart performed best in identifying infants at increased risk of adverse perinatal outcome in a preterm population. METHODS AND FINDINGS: We conducted a retrospective cohort study of all preterm infants born at 24.0 to 36.9 weeks gestation in Victoria, Australia, from 2005 to 2015 (28,968 records available for analysis). All above growth charts were applied to the population. Proportions classified as <5th centile and <10th centile by each chart were compared, as were proportions of stillborn infants considered small for gestational age (SGA, <10th centile) by each chart. We then compared the relative performance of non-overlapping SGA cohorts by each chart to our low-risk reference population (infants born appropriate size for gestational age [>10th and <90th centile] by all intrauterine charts [AGAall]) for the following perinatal outcomes: stillbirth, perinatal mortality (stillbirth or neonatal death), Apgar <4 or <7 at 5 minutes, neonatal intensive care unit admissions, suspicion of poor fetal growth leading to expedited delivery, and cesarean section. All intrauterine charts classified a greater proportion of infants as <5th or <10th centile than birthweight charts. The magnitude of the difference between birthweight and fetal charts was greater at more preterm gestations. Of the fetal charts, GROW customised charts classified the greatest number of infants as SGA (22.3%) and the greatest number of stillborn infants as SGA (57%). INTERGROWTH classified almost no additional infants as SGA that were not already considered SGA on GROW or WHO charts; however, those infants classified as SGA by INTERGROWTH had the greatest risk of both stillbirth and total perinatal mortality. GROW customised charts classified a larger proportion of infants as SGA, and these infants were still at increased risk of mortality and adverse perinatal outcomes compared to the AGAall population. Consistent with similar studies in this field, our study was limited in comparing growth charts by the degree of overlap, with many infants classified as SGA by multiple charts. We attempted to overcome this by examining and comparing sub-populations classified as SGA by only 1 growth chart. CONCLUSIONS: In this study, fetal charts classified greater proportions of preterm and stillborn infants as SGA, which more accurately reflected true fetal growth restriction. Of the intrauterine charts, INTERGROWTH classified the smallest number of preterm infants as SGA, although it identified a particularly high-risk cohort, and GROW customised charts classified the greatest number at increased risk of perinatal mortality.

Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life.

BACKGROUND: Women with previous gestational diabetes mellitus (GDM) have evidence of postpartum ß-cell dysfunction, which increases their risk of developing type 2 diabetes (T2DM) later in life. Elevated levels of circulating cell-free preproinsulin (INS) DNA correlate with dying ß-cells in both mice and humans. The aim of this study was to determine if cell-free circulating INS DNA levels are higher in women with previous GDM who develop T2DM. METHODS: We used droplet digital (dd) PCR to measure the levels of cell-free circulating methylated and unmethylated INS DNA in plasma from 97 women with normal glucose tolerance (NGT), 12 weeks following an index GDM pregnancy. Women were assessed for up to 10 years for the development of T2DM. RESULTS: In the follow-up period, 22% of women developed T2DM. Compared with NGT women, total cell-free INS DNA levels were significantly higher in women who developed T2DM (P = 0.02). There was no difference in cell-free circulating unmethylated and methylated INS DNA levels between NGT women and women who developed T2DM (P = 0.09 and P = 0.07, respectively). CONCLUSIONS: In women with a previous index GDM pregnancy, postpartum levels of cell-free circulating INS DNA are significantly higher in those women who later developed T2DM.

Do Postpartum Levels of Apolipoproteins Prospectively Predict the Development of Type 2 Diabetes in Women with Previous Gestational Diabetes Mellitus?

AIMS: The risk of developing type 2 diabetes is greater in women with previous gestational diabetes mellitus (GDM). Apolipoprotein (Apo) species have been associated with the development of type 2 diabetes in the general population. The aim of this study was to determine if circulating levels of Apo species can predict development of type 2 diabetes in women with previous GDM. METHODS: Apo AI, Apo AII, Apo B, Apo CII, Apo CIII and Apo E levels were measured in 95 women with normal glucose tolerance, 12 weeks following an index GDM pregnancy. Women were assessed for up to 10 years for the development of type 2 diabetes. RESULTS: Postpartum Apo CIII levels, and Apo CIII/Apo AI, Apo CIII/Apo AII, Apo CIII/Apo CII, Apo CIII/Apo E and Apo E/Apo CIII ratios were significantly and positively associated with the development of type 2 diabetes. After controlling for age and BMI, these associations, except for the Apo E/Apo CIII ratio, remained significant. In a clinical model of prediction of type 2 diabetes that included age, BMI, and pregnancy and postnatal fasting glucose, the addition of Apo CIII levels, Apo CIII/Apo AI, Apo CIII/Apo AII, Apo CIII/Apo CII, and Apo CIII/Apo E resulted in a net reclassification improvement of 16.2%. CONCLUSIONS: High Apo CIII levels and the Apo CIII/Apo AI, Apo CIII/Apo AII, Apo CIII/Apo CII, and Apo CIII/Apo E ratios are all significant risk factors for the development of type 2 diabetes in women with a previous GDM pregnancy.

Depression across pregnancy and the postpartum, antidepressant use and the association with female sexual function.

BACKGROUND: There is an established relationship between depression and sexual functioning in women. However, there is limited research examining the relationship between perinatal depression and sexual functioning. METHODS: This study draws on the Mercy Pregnancy and Emotional Wellbeing Study and reports on 211 women recruited in early pregnancy and followed to 12 months postpartum. Women were assessed for depression using the Structured Clinical Interview for the DSM-IV, repeated measurement of depressive symptoms using the Edinburgh Postnatal Depression Scale and sexual functioning using the Female Sexual Functioning Inventory. Data were also collected on antidepressant use, mode of delivery, history of childhood trauma, breastfeeding and partner support. RESULTS: Women showed a decline in sexual functioning over pregnancy and the first 6 months postpartum, which recovered by 12 months. For women with depression, sexual functioning was lower throughout pregnancy and continued to be lower at 6 months postpartum than those without depression. Ongoing depressive symptoms at 12 months were also associated with lower sexual functioning. Sexual functioning was not predicted by mode of delivery, antidepressant use or childhood trauma. Breastfeeding predicted lower sexual functioning only at 6 months. Higher partner support predicted higher female sexual functioning. CONCLUSIONS: Pregnancy and the postpartum are a time of reduced sexual functioning for women; however, women with depression are more likely to have lower levels of sexual functioning and this was not predicted by antidepressant use. In women with perinatal depression, consideration of the impact on sexual functioning should be an integral part of care.

Customised growth charts in large-for-gestational-age infants and the association with emergency caesarean section rate.

BACKGROUND AND AIM: Large-for-gestational-age (LGA) infants are at increased risk of intrapartum complications. However, some infants classified as LGA may be appropriate-for-gestational-age (AGA) if adjusted for maternal stature. We determined whether customisation of birthweight centiles by maternal height, or height and weight, improves the detection of LGA infants at risk of complications. METHODS: We conducted a retrospective analysis of 38 246 term, singleton nulliparous women. We compared population birthweight centiles to those customised by height, or height and weight for complications including intrapartum caesarean section, instrumental delivery, postpartum haemorrhage, anal sphincter injury and neonatal outcomes. RESULTS: Those considered LGA when customised for height but AGA by population centiles (LGA-ht-only) were at increased risk of intrapartum emergency caesarean section compared with infants AGA on all charts (AGA-all); odds ratio (OR) 4.64, 95% CI 3.22-6.76. In contrast, infants considered LGA on population charts, but AGA when customised by height (LGA-pop-only) were not at increased risk compared to the AGA-all group (OR 1.43, 95% CI 0.70-1.88). Infants classified as LGA-ht-only compared to LGA-pop-only remained at significantly higher risk after adjustment for potential confounders (aOR 3.27; 95% CI 2.02-5.31). No difference was seen for any other outcomes. No benefit was seen with customisation by both maternal height and weight. CONCLUSION: Women with an infant classified as AGA on population centiles but LGA when customised for height are at increased risk of intrapartum caesarean section. This is a population unrecognised in current practice. Fetal growth should be customised for maternal height when making assessments regarding the LGA infant.

Preconception management of women with obesity: A systematic review.

The prevalence of women of child-bearing age with obesity continues to rise at an alarming rate. This has significant implications for both the short-term and long-term health of mother and offspring. Given the paucity of evidence-based literature in this field, the preconception management of women with obesity is highly variable both between institutions and around the world. This systematic review aims to evaluate studies that inform us about the role of preconception weight loss in the fertility and pregnancy outcomes of women with obesity. Current therapeutic interventions are discussed, with a specific focus on the suitability of weight loss interventions for women with obesity planning pregnancy. There are significant knowledge gaps in the current literature; these are discussed and areas for future research are explored.

Health consequences for mother and baby of substantial pre-conception weight loss in obese women: study protocol for a randomized controlled trial.

BACKGROUND: Current guidelines for the management of obesity in women planning pregnancy suggest lifestyle modification before conception. However, there is little evidence that lifestyle modification alters pregnancy outcomes. Bariatric surgery results in significant weight loss. This appears to reduce the risk of adverse pregnancy outcomes for the mother but may increase the risk of adverse outcomes for the infant. In order to reduce the risks of obesity-related adverse pregnancy outcomes for both mother and offspring, alternative approaches to the management of obesity in women planning pregnancy are needed. METHODS/DESIGN: This study, a two-arm, parallel group, randomized control trial, will be conducted at the Metabolic Disorders Centre, University of Melbourne. This trial will recruit 164 women aged 18-38 years with a body mass index of 30-55 kg/m2 who plan to conceive in the next 6-12 months. Women will be randomized to one of two 12-week interventions (Group A and Group B). Group A will aim for modest weight loss (MWL; ≤ 3% body weight) using a hypocaloric diet. Group B will aim for substantial weight loss (SWL; 10-15% body weight) using a modified very low energy diet (VLED) program. All participants will be asked to comply with National Health and Medical Research Council (NHMRC) guidelines for exercise and will be provided with standard pre-pregnancy advice according to Royal Australian and New Zealand College of Obstetrics and Gynaecology guidelines. All participants will then be observed for the subsequent 12 months. If pregnancy occurs within the 12-month follow-up period, data on weight and metabolic status of the mother, and pregnancy outcomes of mother and offspring will be recorded. The primary outcome is maternal fasting plasma glucose at 26-28 weeks' gestation, given that this is known to correlate with pregnancy outcomes. Time to conception, live birth rate, gestational weight gain, and a composite of adverse pregnancy outcomes for mother and baby will comprise the secondary outcomes. DISCUSSION: There is increasing emphasis on obese women losing weight before conception. To date, no randomized controlled trial has demonstrated an effective means of weight loss that results in improved pregnancy outcomes for both mother and baby. This study intends to determine if substantial pre-conception weight loss, achieved using a VLED, improves pregnancy outcomes for mother and baby when compared with standard care. This research will potentially change clinical care of an obese woman planning pregnancy. TRIAL REGISTRATION: ANZCTR, 12,614,001,160,628 . Registered on 5 November 2014.

Why we miss fetal growth restriction: Identification of risk factors for severely growth-restricted fetuses remaining undelivered by 40 weeks gestation.

BACKGROUND: Severe fetal growth restriction (FGR) is a leading cause of adverse perinatal morbidity and mortality; however, in Victoria, 35% of severely growth-restricted infants are undelivered by 40 weeks gestation. AIMS: We aimed to identify factors associated with failure to deliver severely growth-restricted fetuses by 40 weeks gestation. METHODS: We conducted a retrospective case-control study of term singletons born <3rd centile for gestation at a single tertiary centre (2010-2017). Infants with a planned delivery for FGR between 37.0-39.6  weeks gestation ('planned birth' group; n = 187) were compared with those undelivered by 40.0  weeks ('undelivered' group; n = 233). Variables assessed included the presence of risk factors for FGR, model of care, symphyseal-fundal height measurements and third trimester ultrasounds. RESULTS: An equivalent proportion of women were 'high-risk' for FGR on history (31.3% vs 38.0%, P = 0.187) in the planned and undelivered groups. Women booked under low-risk models (shared care and midwifery-led care) were significantly more likely to be in the undelivered group compared to those booked under traditional collaborative models (79.8% vs 37.4%, P < 0.001). Women in the undelivered group were less likely to have received a third trimester ultrasound (93.0% vs 40.3%, P < 0.001); however, they were more likely to have had a reassuring ultrasound with an estimation of fetal weight or abdominal circumference >10th centile (78.7% vs 16.1%, P < 0.001). CONCLUSIONS: Failure to deliver the severely growth-restricted fetus before 40.0 weeks is more likely to occur in the following situations: (i) failure to receive an indicated third trimester ultrasound; (ii) the presence of falsely reassuring third trimester ultrasound scan; and (iii) booking under a low-risk rather than traditional collaborative models of care.

How common is substantial weight gain after pregnancy?

BACKGROUND: Although population-based studies indicate that on average, women gain 1-2kg between pregnancies, women with obesity often attribute its development to childbearing. There is little contemporary data available regarding how commonly this occurs, particularly in women of different body mass index (BMI) categories. The aim of this study was to examine inter-pregnancy weight changes among women at a tertiary obstetric hospital in Melbourne, Australia. METHODS: This was a retrospective review of data from the Birthing Outcomes System electronic record of 19,617 women aged 20 years or older, who delivered at least two consecutive singleton infants at ≥37 weeks' gestation at Mercy Hospital for Women between December 1994 and December 2015. A logistic regression model was used to assess the relationship between gain of ≥4kg/m2 between pregnancies and maternal BMI category in the first pregnancy, adjusting for covariates of maternal age, inter-pregnancy interval, and socioeconomic status. RESULTS: Gain of ≥4kg/m2 between the first two pregnancies occurred in 7.5% of normal weight women, 10.5% of overweight women, and 13.4% of women with obesity. One in five women who were normal weight in their first pregnancy increased to overweight or obese BMI categories in their second pregnancy. CONCLUSIONS: Substantial weight gain in relation to pregnancy affects a considerable proportion of women. Since inter-pregnancy weight gain is associated with several complications in the next pregnancy and longer term, avoiding excessive weight gain during and between pregnancies may prevent adverse health consequences in mothers and offspring.

Mercy Pregnancy and Emotional Well-being Study (MPEWS): Understanding maternal mental health, fetal programming and child development. Study design and cohort profile.

Maternal mental health represents a significant global health burden. The Mercy Pregnancy and Emotional Well-being Study (MPEWS) was established to provide a comprehensive investigation of early developmental mechanisms and modifiers for maternal, fetal and child emotional well-being. MPEWS is a prospective, longitudinal study from pregnancy to 36 months postpartum that includes diagnostic measures of maternal mental health, observational measures of the mother-infant relationship, measures of child development, and repeat biological sampling. A total of 282 pregnant women were recruited in early pregnancy from the Mercy Hospital for Women in Melbourne, Australia, including 52 women on antidepressant medication, 31 non-medicated women meeting diagnostic criteria for current unipolar depression or dysthymia, and 65 women with a past history of depression. Sample recruitment characteristics included a mean age of 31 years and average gestation of 16 weeks. The MPEWS cohort was comparable to national averages for Australia on key pregnancy and birth variables. Those participants taking antidepressant medication had higher mean Edinburgh Postnatal Depression Scale (EPDS) and State Trait Anxiety Inventory (STAI) scores than the cohort as a whole but were comparable on other key variables. The MPEWS protocol provides a unique opportunity to evaluate the impact of pregnancy mental health on future maternal mental health and child development to aid the development of evidence-based interventions. The study is open for collaborative proposals via approach to the principal investigators.

Predicting Preterm Labour: Current Status and Future Prospects.

Preterm labour and birth are a major cause of perinatal morbidity and mortality. Despite modern advances in obstetric and neonatal management, the rate of preterm birth in the developed world is increasing. Yet even though numerous risk factors associated with preterm birth have been identified, the ability to accurately predict when labour will occur remains elusive, whether it is at a term or preterm gestation. In the latter case, this is likely due to the multifactorial aetiology of preterm labour wherein women may display different clinical presentations that lead to preterm birth. The discovery of novel biomarkers that could reliably identify women who will subsequently deliver preterm may allow for timely medical intervention and targeted therapeutic treatments aimed at improving maternal and fetal outcomes. Various body fluids including amniotic fluid, urine, saliva, blood (serum/plasma), and cervicovaginal fluid all provide a rich protein source of putative biochemical markers that may be causative or reflective of the various pathophysiological disorders of pregnancy, including preterm labour. This short review will highlight recent advances in the field of biomarker discovery and the utility of single and multiple biomarkers for the prediction of preterm birth in the absence of intra-amniotic infection.

Human cervicovaginal fluid biomarkers to predict term and preterm labor.

Preterm birth (PTB; birth before 37 completed weeks of gestation) remains the major cause of neonatal morbidity and mortality. The current generation of biomarkers predictive of PTB have limited utility. In pregnancy, the human cervicovaginal fluid (CVF) proteome is a reflection of the local biochemical milieu and is influenced by the physical changes occurring in the vagina, cervix and adjacent overlying fetal membranes. Term and preterm labor (PTL) share common pathways of cervical ripening, myometrial activation and fetal membranes rupture leading to birth. We therefore hypothesize that CVF biomarkers predictive of labor may be similar in both the term and preterm labor setting. In this review, we summarize some of the existing published literature as well as our team's breadth of work utilizing the CVF for the discovery and validation of putative CVF biomarkers predictive of human labor. Our team established an efficient method for collecting serial CVF samples for optimal 2-dimensional gel electrophoresis resolution and analysis. We first embarked on CVF biomarker discovery for the prediction of spontaneous onset of term labor using 2D-electrophoresis and solution array multiple analyte profiling. 2D-electrophoretic analyses were subsequently performed on CVF samples associated with PTB. Several proteins have been successfully validated and demonstrate that these biomarkers are associated with term and PTL and may be predictive of both term and PTL. In addition, the measurement of these putative biomarkers was found to be robust to the influences of vaginal microflora and/or semen. The future development of a multiple biomarker bed-side test would help improve the prediction of PTB and the clinical management of patients.

Concordance of maternal and paternal decision-making and its effect on choice for vaginal birth after caesarean section.

BACKGROUND: The proportion of women who plan for a repeat elective caesarean section (CS) is one of the major determinants of the overall rate of CS, and programs aiming to reduce the rate of CS have not been greatly successful. To date, there appear to have been no large studies directly addressing paternal influences on decision-making regarding vaginal birth after caesarean (VBAC). This study aimed to compare the reactions of fathers and mothers to the prospect of VBAC. METHODS: Couples were recruited from three Australian hospitals and were eligible with a singleton pregnancy, a normal morphology ultrasound, and where there was no condition in the new pregnancy that would preclude a vaginal birth. Questionnaires were scheduled for 20 weeks' gestation, 32-36 weeks' gestation and six weeks postnatal and were sent separately to each partner. RESULTS: Seventy-five couples completed the full sets of questionnaires during the study period. In total, 31 women (41%) ultimately attempted vaginal delivery, and 44 (59%) were delivered by planned CS. When the paternal rating of risk fell between the second and third trimesters, the couple were likely to attempt VBAC (P < 0.05). Where the maternal rating of importance was 3 or less, 92% had a planned CS compared to 63% for the same paternal scores (P = 0.02). CONCLUSION: This study suggests that interventions that improve the paternal perceptions of risk during a pregnancy might increase the chance that a couple will attempt VBAC.

Pregnancy associated plasma protein-A links pregnancy and melanoma progression by promoting cellular migration and invasion.

Melanoma is the most common cancer diagnosed in pregnant women and an aggressive course with poorer outcomes is commonly described during pregnancy or shortly after childbirth. The underlying mechanisms for this are not understood. Here, we report that melanoma migration, invasiveness and progression are promoted by Pregnancy-Associated Plasma Protein-A (PAPPA), a pregnancy-associated metalloproteinase produced by the placenta that increases the bioavailability of IGF1 by cleaving it from a circulating complex formed with IGFBP4. We show that PAPPA is widely expressed by metastatic melanoma tumors and is elevated in melanoma cells exhibiting mesenchymal, invasive and label-retaining phenotypes. Notably, inhibition of PAPPA significantly reduced invasion and migration of melanoma cells in vitro and in vivo within the embryonic chicken neural tube. PAPPA-enriched pregnancy serum treatment enhanced melanoma motility in vitro. Furthermore, we report that IGF1 can induce the phenotypic and functional effects of epithelial-to-mesenchymal transition (EMT) in melanoma cells. In this study, we establish a clear relationship between a pregnancy-associated protein PAPPA, melanoma and functional effects mediated through IGF1 that provides a plausible mechanism for accelerated melanoma progression during pregnancy. This opens the possibility of targeting the PAPPA/IGF1 axis therapeutically.

The prediction of type 2 diabetes in women with previous gestational diabetes mellitus using lipidomics.

AIMS/HYPOTHESIS: The risk of developing diabetes is greater for women with previous gestational diabetes mellitus (GDM). In the general population, plasma lipidomic analysis can identify individuals at risk of developing type 2 diabetes. The aim of this study was to determine whether circulating lipid levels 12 weeks following a GDM pregnancy were associated with an increased risk of developing type 2 diabetes. METHODS: Plasma lipid profiles containing >300 lipids were measured in 104 normal glucose-tolerant women 12 weeks following an index GDM pregnancy using electrospray-ionisation tandem mass spectrometry. Women were assessed for 10 years for development of overt type 2 diabetes. RESULTS: Among the 104 women with previous GDM, 21 (20%) developed diabetes during the median follow-up period of 8.5 years. Three lipid species, the cholesteryl ester species CE 20:4, the alkenylphosphatidylethanolamine species PE(P-36:2) and the phosphatidylserine species PS 38:4, were independently and positively associated with the development of type 2 diabetes. In a clinical model of prediction of type 2 diabetes that included age, BMI, and levels of pregnancy fasting glucose, postnatal fasting glucose, triacylglycerol and total cholesterol, the addition of these three lipid species resulted in an improvement in the net reclassification index of 22.3%. CONCLUSIONS/INTERPRETATION: The lipid species CE 20:4, PE(P-36:2) and PS 38:4 were significant risk factors for the development of type 2 diabetes in women with a previous history of GDM. This report is the first to use plasma lipidomic analysis to identify individual lipids as potential biomarkers for the prediction of type 2 diabetes in women with a history of GDM.