FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail. Hence, this study aimed to investigate the role of FKBPL and SIRT-1 in pre-gestational (type 1 diabetes mellitus, T1D) and gestational diabetes mellitus (GDM). Placental protein expression of important angiogenesis proteins, FKBPL, SIRT-1, PlGF and VEGF-R1, was determined from pregnant women with GDM or T1D, and in the first trimester trophoblast cells exposed to high glucose (25 mM) and varying oxygen concentrations [21%, 6.5%, 2.5% (ACH-3Ps)]. Endothelial cell function was assessed in high glucose conditions (30 mM) and following FKBPL overexpression. Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 was significantly downregulated (p<0.05) even when adjusted for gestational age (r=-0.92, p=0.001). Both FKBPL and SIRT-1 protein expression was reduced in ACH-3P cells in high glucose conditions associated with 6.5%/2.5% oxygen concentrations compared to experimental normoxia (21%; p<0.05). FKBPL overexpression in endothelial cells (HUVECs) exacerbated reduction in tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05). In conclusion, FKBPL and/or SIRT-1 downregulation in response to diabetic pregnancies may have a key role in the development of vascular dysfunction and associated complications affected by impaired placental angiogenesis.

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

CONTEXT: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies. OBJECTIVE: To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44. DESIGN AND INTERVENTION: FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling. SETTINGS AND PARTICIPANTS: Human samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid. MAIN OUTCOME MEASURES: Preeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed. RESULTS: The CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis. CONCLUSIONS: The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.

Placental vascularization indices and prediction of pre-eclampsia in high-risk women.

OBJECTIVE: To assess ability of first and second trimester Placental Vascularization Indices (PVIs) to predict pre-eclampsia (PE) in high-risk pregnancies. METHOD: PVIs derived from 3-Dimensional power Doppler imaging were measured at 11+0-13 + 6 (n = 194) and 19+0-21 + 6 weeks (n = 195). Logistic regression (LR) models used PE as the outcome. To quantify added value of PVIs to baseline characteristics in predicting PE, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices were calculated. RESULTS: Overall rate of PE was 12% (n = 26). Lower first trimester PVIs were seen in women with PE (mean, SD); Vascularization Index (VI,%): 10.0 (6.2) v 14.7 (7.6), P = 0.005, Flow Index (FI): 37.7 (9.1) v 42.9 (10.4), P = 0.03, Vascularization Flow Index (VFI): 3.8 (2.5) v 6.6 (4.0), P < 0.001). All first trimester PVIs predicted PE in LR models adjusted for covariates. IDI and NRI analyses confirmed added clinical utility of VI (IDI 0.05, P = 0.004; NRI 0.66, P < 0.001) and VFI (IDI 0.06, P = 0.004; NRI 0.53, P = 0.91). In the second trimester, FI was lower in women with PE (39.6 (9.1) v 44.4 (8.6), P = 0.01) and predicted PE in adjusted LR models (standardised OR 0.53, 95% CI 0.29-0.97, P = 0.04). FI discriminated between cases and non-cases of PE (IDI 0.04, P = 0.04). CONCLUSION: First trimester placental vascularization indices (VI, FI and VFI) have the potential to predict PE in high-risk pregnancies, with FI remaining predictive in the second trimester.

Maternal vitamin D and neonatal anthropometrics and markers of neonatal glycaemia: Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks' gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks' gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.

Postnatal Lifestyle Intervention for Overweight Women With Previous Gestational Diabetes: A Randomized Controlled Trial.

Background: Gestational diabetes mellitus (GDM) is associated with a sevenfold increased lifetime risk of type 2 diabetes. Excessive gestational weight gain and postpartum weight retention are established predictors of long-term obesity. Objective: To determine the impact of a postnatal lifestyle intervention program for overweight women with previous gestational diabetes mellitus (PAIGE). Design: Postnatal overweight women with previous GDM participated in a multicenter randomized controlled trial between June 2013 and December 2014. The intervention comprised a 1-hour educational program, a free 3-month referral to a commercial weight management organization (Slimming World), a pedometer, and structured telephone and text support, in addition to usual care. The control group received usual care only. The primary outcome was weight loss at 6 months. Results: Sixty women were randomized (29 intervention; 31 control) in two centers based on their week of attendance. The intervention group demonstrated significant weight loss at 6 months after randomization compared with the control group: mean ±SD, 3.9 ± 7.0 kg vs 0.7 ±3.8 kg (P = 0.02). Blood glucose levels did not significantly differ. With respect to well-being measures, a bodily pain was significantly reduced in the intervention group (P = 0.007). Conclusions: PAIGE resulted in significantly greater weight loss at 6 months compared with usual care. Such weight loss could prove beneficial in terms of better long-term health and subsequent prevention of type 2 diabetes in overweight women with previous GDM. Future interventions must consider recruitment strategies, timing of the intervention, and inclusion of partners and/or other family members.

Exploring knowledge of pre-eclampsia and views on a potential screening test in women with type 1 diabetes.

OBJECTIVE: to explore knowledge of pre-eclampsia and opinions on potential screening tests for pre-eclampsia in women with type 1 diabetes. DESIGN: a qualitative study using semi-structured interviews of women planning a pregnancy, currently pregnant or post-partum with experience of pre-eclampsia. SETTING, PARTICIPANTS AND METHODS: eleven women with type 1 diabetes were recruited from a pre-pregnancy planning clinic or antenatal clinic. Semi-structured interviews were conducted with the women, asking a series of open-ended questions about their current knowledge of pre-eclampsia and their views on screening for pre-eclampsia. Data analysis was conducted using inductive thematic analysis. FINDINGS: four main themes were identified: Information, sources of stress, awareness and acceptability of screening. Generally, women's knowledge of pre-eclampsia was limited. Most did not appear to be aware of their increased risk of developing the disease. Similarly, the majority of women were unaware as to why their blood pressure and urine were checked regularly. The introduction of a screening test for pre-eclampsia was favoured, with only a small number of women raising concerns related to the screening tests. CONCLUSIONS: health care professionals need to raise awareness of pre-eclampsia in this high risk group. The introduction of a screening test for pre-eclampsia appears to be acceptable in this population, however, further research is required to validate these findings and also to explore the views of women in other high risk groups.

Impact of an educational DVD on anxiety and glycaemic control in women diagnosed with gestational diabetes mellitus (GDM): A randomised controlled trial.

AIMS: The diagnosis of gestational diabetes mellitus (GDM) during pregnancy can lead to anxiety. This study evaluated the impact of an innovative patient-centred educational DVD on anxiety and glycaemic control in women newly diagnosed with GDM. METHODS: 150 multi-ethnic women, aged 19-44years, from three UK hospitals were randomised to either usual care plus DVD (DVD group, n=77) or usual care alone (control group, n=73) at GDM diagnosis. Primary outcomes were anxiety (State-Trait Anxiety Inventory) and mean 1-h postprandial capillary self-monitored blood glucose for all meals, on day prior to follow-up. RESULTS: No significant difference between the DVD and control group were reported, for anxiety (37.7±11.7 vs 36.2±10.9; mean difference after adjustment for covariates (95% CI) 2.5 (-0.8, 5.9) or for mean 1-h postprandial glucose for all meals (6.9±0.9 vs 7.0±1.2mmol/L; -0.2 (-0.5, 0.2). However, the DVD group had significantly lower postprandial breakfast glucose compared to the control group (6.8±1.2 vs 7.4±1.9mmol/L; -0.5 (-1.1, -<0.1; p=0.04). CONCLUSIONS: The results in this trial did not highlight any differences between those who received the intervention and those who received usual care. It is possible that women already felt supported by their frequent attendance at specialist clinics for monitoring and advice. Healthcare professional and family support are key elements to empowering women with GDM and require further consideration in future interventions. Nonetheless, educational resources such as this will be beneficial to help support women given the current resource and time implications of the year on year rises in the incidence of gestational diabetes.

How do women feel about being weighed during pregnancy? A qualitative exploration of the opinions and experiences of postnatal women.

OBJECTIVE: to explore routine weighing in antenatal care and weight management in pregnancy with women who have been weighed during pregnancy. DESIGN: a qualitative study utilising semi-structured telephone interviews, and thematic analysis. SETTING: participants resided in Dublin, Ireland and had been weighed during pregnancy. PARTICIPANTS: individual telephone interviews conducted with ten postpartum women (nine months postpartum). FINDINGS: experiences of routine weighing were positive, and participants believed it should be part of standard antenatal care. Several benefits to routine weighing were cited, including providing reassurance and minimising postpartum weight retention. It was felt that there was a lack of information provided on gestational weight gain and healthy lifestyle in pregnancy, and that healthcare professionals are ideally placed to provide this advice. Increased information provision was seen as a method to improve healthy lifestyle behaviours in pregnancy. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: these findings contribute to the current debate about the re-introduction of routine weighing throughout pregnancy (Allen-Walker et al., 2016). Women stated that they expected to be weighed during pregnancy and, contrary to previous claims, there was no evidence that routine weighing during antenatal care caused anxiety. From discussions it was clear that women desired more information on gestational weight gain and a healthy lifestyle, and felt that health professionals should provide this.

Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women With Type 1 Diabetes.

OBJECTIVE: To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks' gestation, respectively). RESULTS: FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6-21.4] vs. 12.7 ng/mL [interquartile range 9.6-17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6-25.8] vs. 14.6 ng/mL [interquartile range 10.8-19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24-6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester. CONCLUSIONS: Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes.

Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes. OBJECTIVES: To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes. SEARCH STRATEGY: We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity. MAIN RESULTS: A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful. CONCLUSIONS: Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy.

Placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes: The effect of vitamin C and E supplementation.

AIM: In view of the increased rates of pre-eclampsia observed in diabetic pregnancy and the lack of ex vivo data on placental biomarkers of oxidative stress in T1 diabetic pregnancy, the aim of the current investigation was to examine placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes. A further objective of the study was to investigate the putative impact of vitamin C and E supplementation on antioxidant enzyme activity and lipid peroxidation in type 1 diabetic placentae. METHODS: The current study measured levels of antioxidant enzyme [glutathione peroxidase (Gpx), glutathione reductase (Gred), superoxide dismutase (SOD) and catalase] activity and degree of lipid peroxidation (aqueous phase hydroperoxides and 8-iso-prostaglandin F2α) in matched central and peripheral samples from placentae of DAPIT (n=57) participants. Levels of vitamin C and E were assessed in placentae and cord blood. RESULTS: Peripheral placentae demonstrated significant increases in Gpx and Gred activities in pre-eclamptic in comparison to non-pre-eclamptic women. Vitamin C and E supplementation had no significant effect on cord blood or placental levels of these vitamins, nor on placental antioxidant enzyme activity or degree of lipid peroxidation in comparison to placebo-supplementation. CONCLUSION: The finding that maternal supplementation with vitamin C/E does not augment cord or placental levels of these vitamins is likely to explain the lack of effect of such supplementation on placental indices including antioxidant enzymes or markers of lipid peroxidation.

Parent ratings of child cognition and language compared with Bayley-III in preterm 3-year-olds.

BACKGROUND: Parent ratings on questionnaires may provide valid and cost-effective tools for screening cognitive development of children at risk of developmental delay. AIMS: In this study, we examined the convergent validity of combining parent-based reports of non-verbal cognitive abilities (PARCA3) and verbal abilities (CDI-III) in relation to the Bayley-III cognitive scale in 3-year-olds born late pre-term. METHODS: Mothers of 185 late-preterm children were asked to complete the PARCA3 and the CDI-III shortly before children reached age three; children were then assessed using the Bayley-III close to their third birthday. RESULTS: The two maternal questionnaires were significantly and moderately correlated with the Bayley-III cognitive scores. Together the maternal ratings accounted for 15% of the variance in the Bayley-III cognitive scores, after controlling for other covariates in regression analysis. In particular, the PARCA3 contributed significantly to explain variance in the Bayley-III cognitive scores when controlling for the CDI-III. However, the CDI-III was also independently associated with the Bayley-III cognitive scores. CONCLUSIONS: Parent ratings of child cognition and language together may provide cost-effective screening of development in "at risk" preschoolers.

Glycemic targets in the second and third trimester of pregnancy for women with type 1 diabetes.

OBJECTIVE: To assess the relationship between second and third trimester glycemic control and adverse outcomes in pregnant women with type 1 diabetes, as uncertainty exists about optimum glycemic targets. RESEARCH DESIGN AND METHODS: Pregnancy outcomes were assessed prospectively in 725 women with type 1 diabetes from the Diabetes and Pre-eclampsia Intervention Trial. HbA1c (A1C) values at 26 and 34 weeks' gestation were categorized into five groups, the lowest, <6.0% (42 mmol/mol), being the reference. Average pre- and postprandial results from an eight-point capillary glucose profile the previous day were categorized into five groups, the lowest (preprandial <5.0 mmol/L and postprandial <6.0 mmol/L) being the reference. RESULTS: An A1C of 6.0-6.4% (42-47 mmol/mol) at 26 weeks' gestation was associated with a significantly increased risk of large for gestational age (LGA) (odds ratio 1.7 [95% CI 1.0-3.0]) and an A1C of 6.5-6.9% (48-52 mmol/mol) with a significantly increased risk of preterm delivery (odds ratio 2.5 [95% CI 1.3-4.8]), pre-eclampsia (4.3 [1.7-10.8]), need for a neonatal glucose infusion (2.9 [1.5-5.6]), and a composite adverse outcome (3.2 [1.3-8.0]). These risks increased progressively with increasing A1C. Results were similar at 34 weeks' gestation. Glucose data showed less consistent trends, although the risk of a composite adverse outcome increased with preprandial glucose levels between 6.0 and 6.9 mmol/L at 34 weeks (3.3 [1.3-8.0]). CONCLUSIONS: LGA increased significantly with an A1C ≥6.0 (42 mmol/mol) at 26 and 34 weeks' gestation and with other adverse outcomes with an A1C ≥6.5% (48 mmol/mol). The data suggest that there is clinical utility in regular measurement of A1C during pregnancy.

Physical activity, sedentary behaviour and fetal macrosomia in uncomplicated pregnancies: a prospective cohort study.

OBJECTIVE: to explore maternal energy balance, incorporating free living physical activity and sedentary behaviour, in uncomplicated pregnancies at risk of macrosomia. METHODS: a parallel-group cross-sectional analysis was conducted in healthy pregnant women predicted to deliver infants weighing ≥ 4000 g (study group) or < 4000 g (control group). Women were recruited in a 1:1 ratio from antenatal clinics in Northern Ireland. Women wore a SenseWear(®) Body Media Pro3 physical activity armband and completed a food diary for four consecutive days in the third trimester. Physical activity was measured in Metabolic Equivalent of Tasks (METs) where 1 MET = 1 kcal per kilogram of body weight per hour. Analysis of covariance (ANCOVA) was employed using the General Linear Model to adjust for potential confounders. FINDINGS: of the 112 women recruited, 100 complete datasets were available for analysis. There was no significant difference in energy balance between the two groups. Intensity of free living physical activity (average METs) of women predicted to deliver macrosomic infants (n = 50) was significantly lower than that of women in the control group (n = 50) (1.3 (0.2) METs (mean, standard deviation) versus 1.2 (0.2) METs; difference in means -0.1 METs (95% confidence interval: -0.19, -0.01); p = 0.021). Women predicted to deliver macrosomic infants also spent significantly more time in sedentary behaviour (≤ 1 MET) than the control group (16.1 (2.8) hours versus 13.8 (4.3) hours; 2.0 hours (0.3, 3.7), p = 0.020). KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: although there was no association between predicted fetal macrosomia and energy balance, those women predicted to deliver a macrosomic infant exhibited increased sedentary behaviour and reduced physical activity in the third trimester of pregnancy. Professionals caring for women during pregnancy have an important role in promoting and supporting more active lifestyles amongst women who are predicted to deliver a macrosomic infant given the known associated risks.

The effectiveness of weight management interventions in breastfeeding women--a systematic review and critical evaluation.

BACKGROUND: The postpartum period is a vulnerable time for excess weight retention, particularly for the increasing number of women who are overweight at the start of their pregnancy and subsequently find it difficult to lose additional weight gained during pregnancy. Although postpartum weight management interventions play an important role in breaking this potentially vicious cycle of weight gain, the effectiveness of such interventions in breastfeeding women remains unclear. Our aim was to systematically review the literature about the effectiveness of weight management interventions in breastfeeding women. METHODS: Seven electronic databases were searched for eligible papers. Intervention studies included were carried out exclusively in breastfeeding mothers, ≤2 years postpartum and with a body mass index greater than 18.5 kg/m(2) , with an outcome measure of change in weight and/or body composition. RESULTS: Six studies met the selection criteria, and were stratified according to the type of intervention and outcome measures. Despite considerable heterogeneity among studies, the dietary-based intervention studies appeared to be the most efficacious in promoting weight loss; however, few studies were tailored toward the needs of breastfeeding women. CONCLUSIONS: Weight management interventions which include an energy-restricted diet may play a key role in successful postpartum weight loss for breastfeeding mothers.

Neonatal intensive care and late preterm infants: health and family functioning at three years.

BACKGROUND: Late preterm infants (LPIs), born at 34+0 to 36+6 weeks of gestation contribute a significant proportion of all neonatal intensive care (NIC) admissions and are regarded as being at risk of adverse outcomes compared to term-born infants. AIM: To explore the health outcomes and family functioning of LPIs who required neonatal intensive care, at three years of age. STUDY DESIGN AND SUBJECTS: This cohort study included 225 children born late preterm, between 1 January and 31 December 2006 in Northern Ireland. Children admitted for NIC (study group, n=103) were compared with children who did not require NIC or who required special care only for up to three days (comparison group, n=122). OUTCOME MEASURES: Health outcomes were measured using the Health Status Questionnaire, health service usage by parent report and family functioning using the PedsQL™ Family Impact Module. RESULTS: LPIs who required NIC revealed similar health outcomes at three years in comparison to those who did not. Despite this, more parents of LPIs who required NIC reported visiting their GP and medical specialists during their child's third year of life. Differences in family functioning were also observed with mothers of LPIs who required NIC reporting, significantly lower levels of social and physical functioning, increased difficulties with communication and increased levels of worry. CONCLUSIONS: LPIs were observed to have similar health outcomes at three years of age regardless of NIC requirement. The increase in GP and medical specialist visits and family functioning difficulties observed among those infants who required NIC merits further investigation.

Women's perceptions and experiences of fetal macrosomia.

OBJECTIVE: to explore women's perceptions and experiences of pregnancy and childbirth following birth of a macrosomic infant (birth weight ≥4000g). METHODS: a qualitative design utilising interviews conducted 13-19 weeks post partum in women's homes. The study was conducted in one Health and Social Care Trust in Northern Ireland between January and September 2010. Participants were identified from a larger cohort of women recruited to a prospective study exploring the impact of physical activity and nutrition on macrosomia. Eleven women who delivered macrosomic infants participated in this phase of the study. FINDINGS: four overarching themes emerged: preparation for delivery; physical and emotional impact of macrosomia; professional relations and perceptions of macrosomia. Findings highlighted the importance of communication with health professionals in relation to both prediction of macrosomia and decision making about childbirth, and offers further understanding into the physical and emotional impact of having a macrosomic infant on women. Furthermore, there was evidence that beliefs and perceptions relating to macrosomia may influence birth experiences and uptake of health promotion messages. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: this study provides important insight into women's experiences of macrosomia throughout the perinatal period and how they were influenced by previous birth experiences, professional relations and personal perceptions and beliefs about macrosomia. Pregnant women at risk of having a macrosomic infant may require extra support throughout the antenatal period continuing into the postnatal period. Support needs to be tailored to the woman's information needs, with time allocated to explore previous birth experiences, beliefs about macrosomia and options for childbirth.

The role of angiogenic and antiangiogenic factors in the second trimester in the prediction of preeclampsia in pregnant women with type 1 diabetes.

OBJECTIVE: To assess the association between circulating angiogenic and antiangiogenic factors in the second trimester and risk of preeclampsia in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Maternal plasma concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) were available at 26 weeks of gestation in 540 women with type 1 diabetes enrolled in the Diabetes and Preeclampsia Intervention Trial. RESULTS: Preeclampsia developed in 17% of pregnancies (n = 94). At 26 weeks of gestation, women in whom preeclampsia developed later had significantly lower PlGF (median [interquartile range]: 231 pg/mL [120-423] vs. 365 pg/mL [237-582]; P < 0.001), higher sFlt-1 (1,522 pg/mL [1,108-3,393] vs. 1,193 pg/mL [844-1,630] P < 0.001), and higher sEng (6.2 ng/mL [4.9-7.9] vs. 5.1 ng/mL[(4.3-6.2]; P < 0.001) compared with women who did not have preeclampsia. In addition, the ratio of PlGF to sEng was significantly lower (40 [17-71] vs. 71 [44-114]; P < 0.001) and the ratio of sFlt-1 to PlGF was significantly higher (6.3 [3.4-15.7] vs. 3.1 [1.8-5.8]; P < 0.001) in women who later developed preeclampsia. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to a logistic model containing established risk factors (area under the curve [AUC], 0.813) significantly improved the predictive value (AUC, 0.850 and 0.846, respectively; P < 0.01) and significantly improved reclassification according to the integrated discrimination improvement index (IDI) (IDI scores 0.086 and 0.065, respectively; P < 0.001). CONCLUSIONS: These data suggest that angiogenic and antiangiogenic factors measured during the second trimester are predictive of preeclampsia in women with type 1 diabetes. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to established clinical risk factors significantly improves the prediction of preeclampsia in women with type 1 diabetes.

Impact of neonatal intensive care on late preterm infants: developmental outcomes at 3 years.

BACKGROUND: Late preterm infants (LPIs) (34-36 weeks' gestation) account for up to 75% of preterm births and constitute a significant proportion of all neonatal admissions. This study assessed the impact of neonatal intensive or high-dependency care (IC) on developmental outcomes of LPIs at 3 years of age. METHODS: This cohort study included 225 children born late preterm in Northern Ireland during 2006. Children born late preterm who received IC were compared with children born late preterm who did not receive IC. Cognitive, motor, and language skills were assessed by using the Bayley Scales of Infant and Toddler Development, Third Edition. Growth was assessed by using anthropometric measures of height and weight. RESULTS: LPIs who received IC were more often less mature (34 weeks' gestation), with lower birth weight (≤ 2500 g) and Apgar scores (<7 at 5 minutes) compared with the control group. They were more often born by cesarean delivery and more likely to have received resuscitation at birth. At 3 years of age, children born late preterm who received IC demonstrated similar cognitive, motor, and language skills compared with children in the control group. Measurements of growth also did not differ significantly between groups. CONCLUSIONS: Despite having increased maternal, perinatal, and neonatal risk factors, there were no significant differences in early childhood development between LPIs who received IC and those who did not. LPIs do not receive routine follow-up after IC and this study provides useful and reassuring data for parents and clinicians on the longer-term outcome of this infant group.