The etiology of stillbirth over 30 years: A cross-sectional study in a tertiary referral unit.

INTRODUCTION: Stillbirth remains an often unpredictable and devastating pregnancy outcome, and despite thorough investigation, the number of stillbirths attributable to unexplained causes remains high. Placental examination has become increasingly important where access to perinatal autopsy is limited. We aimed to examine the causes of stillbirth in normally formed infants over 30 years and whether a declining autopsy rate has affected our ability to determine a cause for stillbirths. MATERIAL AND METHODS: All cases of normally formed singleton infants weighing ≥500 g that died prior to the onset of labor from 1989 to 2018 were examined. Trends for specific causes and uptake of perinatal autopsy were analyzed individually. RESULTS: In all, 229 641 infants were delivered, with 840 stillbirths giving a rate of 3.66/1000. The rate of stillbirth declined from 4.84/1000 in 1989 to 2.51 in 2018 (P < .001). There was no difference in the rate of stillbirth between nulliparous and multiparous women (4.25 vs 3.66 per 1000, P = .026). Deaths from placental abruption fell (1.13/1000 in 1989 to 0 in 2018, P < .001) and the relative contribution of placental abruption to the incidence of stillbirth also fell, from 23.3% (7/30) in 1989 to 0.0% (0/19) in 2018 (P < .001). Stillbirth attributed to infection remained static (0.31/1000 in 1989 to 0.13 in 2018, P = .131), while a specific causal organism was found in 79.2% (42/53) of cases. Unexplained stillbirths decreased from 2.58/1000 (16/6200) in 1989 to 0.13 (1/7581) in 2018 (P < .001) despite a fall in the uptake of perinatal autopsy (96.7% [29/30] in 1989 to 36.8% (7/19) in 2018; P < .001). Placental disease emerged as a significant cause of stillbirth from 2004 onwards (89.5% [17/19] in 2018). CONCLUSIONS: The present analysis is one of the largest single-center studies on stillbirth published to date. Stillbirth rates have fallen across the study period across parity. A decrease in deaths secondary to placental abruption contributed largely to this. Infection-related deaths are static; however, in one-fifth of cases a causative organism was not found. Despite a decreasing autopsy rate, the number of unexplained stillbirths continues to fall as the importance of placental pathology is increasingly recognized.

Identification of those most likely to benefit from a low-glycaemic index dietary intervention in pregnancy.

The present study is a secondary analysis of the ROLO study, a randomised control trial of a low-glycaemic index (GI) diet in pregnancy to prevent the recurrence of fetal macrosomia. The objectives of the present study were to identify which women are most likely to respond to a low-GI dietary intervention in pregnancy with respect to three outcome measures: birth weight; maternal glucose intolerance; gestational weight gain (GWG). In early pregnancy, 372 women had their mid-upper arm circumference recorded and BMI calculated. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. At delivery, infant birth weight was recorded and fetal glucose, C-peptide and leptin concentrations were measured in the cord blood. Women who benefited in terms of infant birth weight were shorter, with a lower education level. Those who maintained weight gain within the GWG guidelines were less overweight in both their first and second pregnancies, with no difference being observed in maternal height. Women who at 28 weeks of gestation developed glucose intolerance, despite the low-GI diet, had a higher BMI and higher glucose concentrations in early pregnancy with more insulin resistance. They also had significantly higher-interval pregnancy weight gain. For each analysis, women who responded to the intervention had lower leptin concentrations in early pregnancy than those who did not. These findings suggest that the maternal metabolic environment in early pregnancy is important in determining later risks of excessive weight gain and metabolic disturbance, whereas birth weight is mediated more by genetic factors. It highlights key areas, which warrant further interrogation before future pregnancy intervention studies, in particular, maternal education level and inter-pregnancy weight gain.

Exploring full cervical dilatation caesarean sections-A retrospective cohort study.

BACKGROUND: The rate of caesarean sections at full cervical dilatation with their high risk of morbidity continues to rise mirroring the overall increase in caesarean section rates internationally. OBJECTIVES: The objectives of this study were to determine the rate of full dilatation caesarean section in a tertiary referral unit and evaluate key labour, maternal and fetal factors potentially linked to those deliveries. We also assessed maternal and fetal morbidity at full dilatation sections. Where possible, these were compared with successful operative vaginal deliveries carried out in theatre to determine key differences. STUDY DESIGN: Retrospective cohort study. We reviewed the rate of full dilatation caesarean section over a 10-year period. We analysed deliveries (caesarean sections or operative vaginal deliveries) in single cephalic pregnancies ≥34 weeks with contemporaneously collected data from our unit's electronic database for 2015. RESULTS: The rate of full dilatation caesarean section increased by over a third in the ten-year period (56/6947 (0.80%) vs 92/7378 (1.24%), p = 0.01). Of 84 full dilatation caesarean sections who met the inclusion criteria, 63 (75%) were nulliparous and the mean maternal age was 33 (±5) years. Oxytocin was used in the second stage in less than half of second stage caesarean sections (22 out of a recorded 57, 38.6%). There were more fetal head malposition (occipito-posterior, or occipito-transverse) at full dilatation caesarean section compared to successful operative vaginal deliveries (41/46 (89.1%) vs 2/21 (9.5), p < 0.001). The rate of significant postpartum haemorrhage (defined as estimated blood loss ≥1000 ml) was similar in both full dilatation caesarean section and operative vaginal deliveries. There was no difference in the mean birthweight at full dilatation caesarean sections compared to operative vaginal delivery (3.88 kg (2.80-5.33 kg) vs 3.48 kg (1.53-4.40 kg)). There was no difference in neonatal morbidity. CONCLUSION: Fetal head malposition is associated with a higher risk of full dilatation caesarean section. Interestingly, maternal and fetal morbidity were similar between full dilatation caesarean sections and anticipated difficult operative vaginal deliveries carried out in theatre. The management of labour in terms of the decision to use oxytocin judiciously in hope of correcting inefficient uterine contractions and continuous labour ward training, particularly the diagnosis of malposition and its correction may be beneficial in reducing the rate of full dilation caesarean sections.

The Effects of Fetal Gender on Maternal and Fetal Insulin Resistance.

OBJECTIVE: Gender plays a role in the development of a number of cardiovascular and metabolic diseases and it has been suggested that females may be more insulin resistant in utero. We sought to assess the relationship between infant gender and insulin resistance in a large pregnancy cohort. STUDY DESIGN: This is a secondary analysis of a cohort from the ROLO randomized control trial of low GI diet in pregnancy. Serum insulin, glucose and leptin were measured in early pregnancy and at 28 weeks. At delivery cord blood C-peptide and leptin were measured. A comparison of maternal factors, fetal biometry, insulin resistance and leptin was made between male and female offspring. A multivariate regression model was built to account for the possible effects of maternal BMI, birthweight and original study group assignment on findings. RESULTS: A total of 582 women were included in this secondary analysis, of whom 304 (52.2%) gave birth to male and 278 (47.8%) gave birth to female infants. Compared to male infants at birth, female infants were significantly lighter, (3945 ± 436 vs. 4081± 549g, p<0.001), shorter in length (52.36 ± 2.3 vs. 53.05 ± 2.4cm, p<0.001) and with smaller head circumferences (35.36 ± 1.5 vs. 36.10 ± 1.1cm, p<0.001) than males. On multiple regression analysis, women pregnant with female fetuses were less insulin resistant in early pregnancy, i.e. had lower HOMA indices (B = -0.19, p = 0.01). Additionally female fetuses had higher concentrations of both cord blood leptin and C-peptide at birth when compared to male offspring (B = 0.38, p<0.001 and B = 0.31, p = 0.03 respectively). CONCLUSION: These findings suggest gender is a risk factor for insulin resistance in-utero. Additionally, carrying a female fetus decreases the risk of insulin resistance in the mother, from as early as the first trimester.

Mode of delivery and outcomes by birth weight among spontaneous and induced singleton cephalic nulliparous labors.

OBJECTIVE: To assess the effect of birth weight on mode of delivery among nulliparous women in a setting with no policy of elective induction for suspected macrosomia. METHODS: In an observational study, data were assessed from nulliparous women with a single cephalic pregnancy of at least 37 weeks in spontaneous (Robson group 1) and induced (Robson group 2a) labor attending a hospital in Dublin, Ireland, between January 1, 2008, and December 31, 2009. The primary outcome measure was mode of delivery. RESULTS: A total of 7528 nulliparous labors were included (4989 in group 1 and 2539 in group 2a). The cesarean section rate was 15.1% overall (n=1139), with 411 (8.2%) in group 1, and 728 (28.7%) in group 2a. Cesarean delivery rates rose with increasing birth weight in group 1, from 119 (6.3%) of 1886 infants weighing 3000-3499 g and 160 (8.5%) of 1892 weighing 3500-3999 g, to 19 (26.8%) of 71 weighing 4500-4999 g. Rates of cesarean delivery were significantly higher in induced labor (group 2a) for each birth-weight category, ranging from 202 (25.9%) of 781 weighing 3000-3499 g and 243 (27.0%) of 899 weighing 3500-3999 g, to 38 (48.1%) of 79 weighing 4500-4999 g (P<0.01 for all). CONCLUSION: In a setting with standardized management of labor, birth weight remains a significant determinant of mode of delivery.

Impact of a low glycemic index diet in pregnancy on markers of maternal and fetal metabolism and inflammation.

This is a secondary analysis of 621 women in ROLO study, a randomized control trial of low glycemic index (GI) diet in pregnancy to prevent the recurrence of macrosomia, which aims to assess the effect of the diet on maternal and fetal insulin resistance, leptin, and markers of inflammation. In early pregnancy and at 28 weeks, serum was analyzed for insulin, leptin, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6). At delivery, cord blood concentrations of leptin, TNF-α, IL-6, and C-peptide were recorded. We found no difference between those who did or did not receive low GI advice with respect to the concentrations of any marker in early pregnancy, at 28 weeks or in cord blood. Women in the intervention arm of the study did have a lower overall rise in insulin concentrations from early pregnancy to 28 weeks gestation, P = .04. Of the women in the intervention arm, 20% were in the highest quartile for insulin change (28-week insulin - insulin at booking) compared to 29% of controls (P = .02). In conclusion, a low GI diet in pregnancy has little effect on leptin and markers of inflammation although an attenuated response to the typical increase in insulin resistance seen in pregnancy with advancing gestation was seen in those who received the low GI advice.

Leptin, fetal growth and insulin resistance in non-diabetic pregnancies.

BACKGROUND: Interrogation of the association between leptin, insulin resistance and fetal growth may provide a biological link for the fetal programming of later metabolic health. AIMS: Our aim was to clarify the relationship between maternal and fetal leptin, insulin resistance and fetal growth. STUDY DESIGN: Maternal leptin, glucose and insulin were measured in early pregnancy and at 28weeks and the HOMA index calculated. At 34weeks, ultrasound scan assessed fetal weight and adiposity (abdominal wall width). At delivery birthweight was recorded and cord blood analyzed for fetal c-peptide and leptin. Analysis was performed using a multivariate linear regression model. SUBJECTS: 574 non-diabetic pregnant women. OUTCOME MEASURES: Fetal growth and maternal and fetal insulin resistance. RESULTS: On multivariate analysis a relationship was identified between maternal and fetal leptin concentrations at each time point and maternal body mass index. Maternal leptin was related to insulin resistance in early pregnancy (ß=0.15, p=0.02) and at 28week gestation (ß=0.27, p<0.001). Fetal insulin resistance correlated with maternal leptin in early pregnancy (ß=0.17, p=0.004); at 28weeks (ß=0.12, p=0.05), and with leptin in cord blood (r=0.28, p<0.001). Fetal weight at 34weeks was related to maternal leptin in early pregnancy (ß=0.16, p=0.02). Both maternal and fetal leptin correlated with infant size at birth (ß=0.12, p=0.07 in early pregnancy, ß=0.21, p=0.004 in cord blood), independent of all other outcome measures. CONCLUSION: Our findings have confirmed that in a non-diabetic cohort there is a link between maternal and fetal leptin and insulin resistance. We also established a link between maternal leptin in early pregnancy and both fetal and neonatal size. These results add to the growing body of evidence suggesting a role for leptin in the fetal programming of childhood obesity and metabolic dysfunction.

Obstetric and metabolic implications of excessive gestational weight gain in pregnancy.

OBJECTIVE: To compare maternal characteristics, obstetric outcomes and insulin resistance in a cohort of women subdivided into those who did and those who did not exceed the Institute of Medicine (IOM) gestational weight gain guidelines. METHODS: This is a prospective study of 621 women without diabetes. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width (AAW). At delivery birthweight was recorded and fetal glucose, C-peptide and leptin measured in cord blood. Insulin resistance was calculated using the HOMA equation. Outcomes in those who did and did not exceed IOM guidelines were compared. RESULTS: Overall, 267 women (43%) exceeded IOM guidelines and 354 (57%) did not. On 34-week ultrasound women with excessive weight gain had higher fetal weights (2681 ± 356 g vs. 2574 ± 331, P = 0.001) and fetal adiposity (AAW) (5.29 ± 1.3 vs. 4.8 ± 1.2, P = 0.001). Infant birthweight and birthweight centiles were also higher in those who exceeded the guidelines. There was no difference between the two groups in maternal insulin resistance in early pregnancy, but by 28 weeks those with excessive weight gain had higher maternal HOMA indices and higher maternal leptin concentrations. CONCLUSION: Excessive maternal gestational weight gain has significant implications for infant growth and adiposity, with potential implications for later adult health.