Thrombocalc: implementation and uptake of personalized postpartum venous thromboembolism risk assessment in a high-throughput obstetric environment.

INTRODUCTION: Venous thromboembolism risk assessment (VTERA) is recommended in all pregnant and postpartum women. Our objective was to develop, pilot and implement a user-friendly electronic VTERA tool. MATERIAL AND METHODS: We developed "Thrombocalc", an electronic VTERA tool using Microsoft EXCEL™ . Thrombocalc was designed as a score-based tool to facilitate rapid assessment of all women after childbirth. Calculation of a total score estimated risk of venous thromboembolism in line with consensus guidelines. Recommendations for thromboprophylaxis were included in the VTERA output. Implementation was phased. Uptake of the VTERA tool was assessed prospectively by monitoring the proportion of women who gave birth in our institution and had a completed risk assessment. Factors affecting completion and accuracy of risk assessments were also assessed. RESULTS: Thrombocalc was used prospectively to risk-assess 8380 women between September 2014 and December 2015. Compliance with this tool increased dramatically throughout the study period; over 92% of women were risk-assessed in the last quarter of data collection. Compliance was not adversely affected if delivery took place out of working hours [adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI) 0.93-1.14]. Risk assessment was less likely in the case of cesarean deliveries (aOR 0.66, 95% CI 0.60-0.73) and stillborn infants (aOR 0.48, 95% CI 0.29-0.79). Misclassification of risk factors led to approximately 207 (2.5%) inaccurate thromboprophylaxis recommendations. CONCLUSIONS: Our electronic, score-based VTERA tool provides a highly effective mechanism for rapid assessment of individual postpartum venous thromboembolism risk in a high-throughput environment.

The effect of maternal subclinical hypothyroidism on IQ in 7- to 8-year-old children: A case-control review.

BACKGROUND: In Ireland, pregnant women are not routinely screened for subclinical hypothyroidism (SCH). AIM: Our objective was to compare the intelligence quotient (IQ) of children whose mothers had been diagnosed with SCH prenatally with matched controls using a case-control retrospective study. MATERIALS AND METHODS: In a previous study from our group, 1000 healthy nulliparous women were screened anonymously for SCH. This was a laboratory diagnosis involving elevated TSH with normal fT4 or normal TSH with hypothyroxinaemia. We identified 23 cases who agreed to participate. These were matched with 47 controls. All children underwent neurodevelopmental assessment at age 7-8. Wechsler Intelligence Scale for Children IV assessment scores were used to compare the groups. Our main outcome measure was to identify whether there was a difference in IQ between the groups. RESULTS: From the cohort of cases, 23 mothers agreed to the assessment of their children as well as 47 controls. The children in the control group had higher mean scores than those in the case group across Verbal Comprehension Intelligence, Perceptual Reasoning Intelligence, Working Memory Intelligence, Processing Speed Intelligence and Full Scale IQ. Mann-Whitney U-test confirmed a significant difference in IQ between the cases (composite score 103.87) and the controls (composite score 109.11) with a 95% confidence interval (0.144, 10.330). CONCLUSIONS: Our results highlight significant differences in IQ of children of mothers who had unrecognised SCH during pregnancy. While our study size and design prevents us from making statements on causation, our data suggest significant potential public health implications for routine prenatal screening.

The correlation of ultrasonographic placental architecture with placental histology in the low-risk primigravid population.

AIM: To determine the association, if any, between placental architecture findings assessed ultrasonographically at 22 and 36 weeks and placental histology. METHODS: There was prospective recruitment of 1011 low-risk primigravids from the antenatal clinic at the Rotunda Hospital, Dublin, Ireland. Ultrasound of the placenta was performed at 22 and 36 weeks and histological assessment was made of the placenta of all participants. RESULTS: Complete data pertaining to ultrasound and placental histology was available for 810 women (80%). Placental calcification on ultrasound in the third trimester was associated with a higher incidence of placental infarction identified following placental histology (80.0% vs. 21.5%; P=0.009: r=0.115). The placental thickness on ultrasound in the second trimester was less in cases complicated by chorioamnionitis (2.62 cm vs. 3.07 cm; P=0.039: r=-0.176). Chronic villitis was associated with a statistically significant increased incidence of antenatal placental infarction identified on ultrasound in the third trimester (10.7% vs. 1.9%; P=0.020: r=0.113). Intervillous thrombi occurred more frequently in cases with reduced placental thickness on ultrasound in the second trimester (3.0 cm vs. 3.3 cm; P=0.035: r=-0.171). CONCLUSIONS: Antenatal ultrasound of the placenta may aid detection of placental disease, particularly in the identification of placental infarction.

Subclinical hypothyroidism as a risk factor for placental abruption: evidence from a low-risk primigravid population.

BACKGROUND: Subclinical thyroid hypofunction in pregnancy has been shown to have an association with neurodevelopmental delay in the offspring. It is unclear whether obstetric factors may account for this observation. AIMS: To establish the prevalence of subclinical hypothyroidism (SCH) in a low-risk primigravid population and to explore its association with obstetric sequelae. MATERIALS AND METHODS: Nine hundred and fifty-three primigravid women had thyroid hormone indices analysed in the early second trimester. Delivery and neonatal outcomes were available for 904 women who met the criteria for inclusion in the study. Women with subclinical hypothyroidism (thyroid-stimulating hormone (TSH) values at or above the 98th percentile with a normal free thyroxine (fT4)) or isolated maternal hypothyroxinaemia (fT4 level at or below the second percentile with a normal-range TSH) were compared with biochemically euthyroid controls. Chi-squared test and analysis of variance were used for statistical analysis. RESULTS: The prevalence of SCH or isolated maternal hypothyroxinaemia was 4%. Positivity for antithyroid peroxidase (TPO) or antithyroglobulin (ATG) antibodies correlated with SCH status (P = 0.02). Placental abruption was observed more commonly in the setting of either SCH or isolated maternal hypothyroxinaemia when compared with euthyroid controls (P = 0.02 and 0.04, respectively). CONCLUSIONS: Subclinical hypothyroidism and isolated maternal hypothyroxinaemia are associated with placental abruption. The observation of these effects in this healthy low-risk population lends weight to the case for antenatal screening for diminished thyroid reserve.

Reviewing the past to inform the future: an 8-year review of severe maternal morbidity.

BACKGROUND: Maternal morbidity is becoming a key indicator used to compare health systems in the developed world and also to inform clinical practice. OBJECTIVE: This study aimed to evaluate a single center experience of severe maternal morbidity over an 8-year period. STUDY DESIGN: We conducted a retrospective review of all cases of severe maternal morbidity from 2012 to 2019 at a tertiary level maternity hospital in the Republic of Ireland with approximately 9000 births per year. We examined maternal demographics, pregnancy characteristics, and care requirements. Descriptive statistics were used throughout. RESULTS: There were 81,504 maternity cases and 67,894 births during the study period. A total of 504 women had a severe maternal morbidity, giving a rate of 6.1 per 1000 maternity cases overall, peaking in 2017 at 8.8 per 1000. When individual severe maternal morbidity events were evaluated, the rate increased from 6 per 1000 to 9 per 1000 over the 8-year period. There were no differences in maternal age, nationality, or body mass index during the years analyzed. Interestingly, 8.9% (n=45) were multiple gestations, and nearly one-fifth (19.4%; n=98) required escalation of care to a general hospital; of these, 14.0% (n=74) required cardiac or intensive care management. The majority of morbidities manifested in the third trimester (58.7%; n=296) or postnatally (42.8%, n=216). The most common severe maternal morbidities were hypertensive disorders of pregnancy, followed by postpartum hemorrhage and sepsis (45.0%, 44.2%, and 12.7%, respectively). CONCLUSION: We provide a longitudinal overview of severe maternal morbidity in a large maternity hospital that replicates other international findings. This information can be used for healthcare comparisons and for resource planning and allocation.

Antenatal suspicion of ischemic placental disease and coexistence of maternal and fetal placental disease: analysis of over 500 cases.

OBJECTIVE: To investigate the antenatal suspicion of placental disease and the coexistence of maternal and fetal placental ischemic disease. STUDY DESIGN: A prospective cohort study on normally formed singleton infants from 2000 to 2008 inclusive with placental ischemic disease. RESULTS: Uteroplacental ischemia or fetoplacental thrombotic vasculopathy was identified in 511 of 74,857 births (7/1000 births). Four hundred fifty-nine cases met the inclusion criteria. Maternal and fetal placental vascular disease coexisted in 9.2% (n = 42) of cases. Placental ischemic disease was suspected antenatally in 70% (324/459). Maternal placental disease occurred in 40% (184/459) and 30% (140/459) had fetal pathology. The perinatal mortality rate was 12.7/1000. Antenatal suspicion of placental disease led to increased obstetric intervention and delivery of small-for-gestational age infants. CONCLUSION: Maternal and fetoplacental vascular disease coexisted in 9.2%. Placental disease was suspected antenatally in 70% of cases and was associated with increased rates of obstetric intervention.

The impact of umbilical and uterine artery Doppler indices on antenatal course, labor and delivery in a low-risk primigravid population.

AIMS: To evaluate the impact of umbilical and uterine artery Doppler in the second and third trimester on antenatal course, labor and delivery in a low-risk primigravid population. METHODS: Prospective recruitment of 1011 low-risk primigravidas with uterine and umbilical artery Doppler assessment at 22-24 weeks and 36 weeks. All mothers and infants were reviewed postnatally with a retrospective analysis of ultrasound and clinical outcome data. RESULTS: Elevated uterine artery indices were associated with increased rates of threatened miscarriage, higher rates of pre-eclampsia (PET) and a higher incidence of fetal birth weight <2nd and 9th centile for gestation. Uterine artery pulsatility index (PI) >95th centile for gestation was associated with statistically higher rates of small-for-gestational age (SGA) infants. Elevated umbilical artery indices were associated with higher rates of induction of labor and a higher incidence of fetal birth weight infants <2nd and 9th centile for gestation. Umbilical artery PI >95th centile for gestation was associated with statistically higher rates of SGA infants. CONCLUSION: Elevated uterine and umbilical artery indices are associated with higher rates of maternal and fetal disease.

The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

AIMS: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.

The incidence and impact of increased body mass index on maternal and fetal morbidity in the low-risk primigravid population.

OBJECTIVE: To determine the incidence and impact of increased body mass index (BMI) on maternal and fetal morbidity in the low-risk primigravid population. METHODS: This was a prospective study with retrospective analysis of delivery outcome data. All low-risk primigravida who met the inclusion criteria during the recruitment period were approached. BMI was calculated using the formula weight/height squared. The participants were divided into five categories: 'underweight' (BMI <20 kg/m2), 'normal' (BMI 20.01-25 kg/m2), 'overweight' (BMI 25.01-30 kg/m2), 'obese' (BMI 30.01-40 kg/m2), and 'morbidly obese' (BMI >40 kg/m2). Maternal outcomes evaluated included gestation at delivery, onset of labor (spontaneous/induced/elective cesarean section), length of labor, use of oxytocin and epidural, mode of delivery, and estimated blood loss. Perinatal outcome measures included infant birth weight (kg) and centile, gestational age, ponderal index, Apgar score <7 at 5 minutes, cord pH <7.1, presence of meconium grade 3 at delivery, degree of resuscitation required, admission to neonatal intensive care unit (NICU), and duration of stay. RESULTS: One thousand and eleven women participated in the study. Complete outcome data were available for 833 women (82%). A significant difference was identified in gestation at delivery between the subgroups (p < 0.004). A significant positive correlation was identified between cesarean section rates with increasing BMI, even when gestation was controlled for (p = 0.004). Similarly, women in the normal BMI group remained significantly less likely to have an infant requiring NICU admission than obese women (2.2% vs. 8.6%; p = 0.011). CONCLUSION: High BMI is associated with longer gestations, higher operative delivery rates, and an increased rate of neonatal intensive care admission

The impact of positive acquired thrombophilia serology on ultrasound, obstetric outcome and the placenta in a low-risk primigravid population.

Our aim was to determine the prevalence and sequelae of positive acquired thrombophilia serology in the asymptomatic low-risk primigravid population. We undertook a prospective blinded study of 1011 primigravid patients screening for lupus anticoagulant, anticardiolipin antibody, anti-ß 2 glycoprotein-1 and antinuclear antibody assessment at booking and 36 weeks gestation. Serial ultrasounds of the fetus with uterine and umbilical Dopplers and placental evaluation were performed at 24 and 36 weeks gestation. Antenatal course, labour and delivery outcome and placental histology were reviewed. The incidence of positive acquired thrombophilia serology was 27.4%. Overall, there was no difference in rates of fetal loss or maternal disease between women with positive acquired thrombophilia serology and the control population. Routine testing for acquired thrombophilic traits is therefore not warranted.

The impact of ultrasonographic placental architecture on antenatal course, labor and delivery in a low-risk primigravid population.

OBJECTIVE: To ascertain the impact of placental architecture on antenatal course and labor delivery in a low-risk primigravid population. METHODS: This study involves prospective recruitment of 1011 low-risk primigravids with placental ultrasound at 22?24 weeks and 36 weeks. Detailed postnatal review of all mothers and infants was undertaken. Retrospective analysis of ultrasound and clinical outcome data was performed. RESULTS: Eight hundred ten women with complete outcome data were available. Anterior placentation was statistically associated with intrauterine growth restriction (IUGR) and preterm birth and fundal placentation was significantly associated with a higher incidence of pregnancy-induced hypertension and infants with a birthweight less than the 9th centile. Placental infarcts in the third trimester was significantly increased in cases complicated by pre-eclampsia (PET) and in cases with fetal acidosis. Placental calcification was associated a 40-fold increase in the incidence of IUGR. Placental lakes in the second trimester were more prevalent in patients with threatened miscarriage. Increased placental thickness was associated with a higher rate of fetal acidosis. The Grannum grade of the placenta was higher with threatened first or second trimester loss, PET and in infants born less than 9th centile for gestation. CONCLUSION: Placental site and architecture impact on the incidence of maternal and fetal disease.

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy.

OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET). METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P < 0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET. RESULTS: There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET. CONCLUSIONS: Maternal IGF-2 has a significant positive correlation with PET.

Illegal drug use, smoking and alcohol consumption in a low-risk Irish primigravid population.

To evaluate the prevalence of illegal drug use, smoking and alcohol consumption in Irish primigravidas, we interviewed 1011 women at their booking visit. A total of 23.5% (235) of women had used illegal drugs prior to their first pregnancy, 28.9% were ex-smokers and 27.9% were still smoking during pregnancy. A total of 53.9% admitted to drinking alcohol during pregnancy. Smokers are 2.8 times more likely to have used drugs in the past than non-smokers. Level of alcohol consumption appears to be a significant predictor of drug use.

Maternal and fetal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3, and their relationship to fetal acidosis at delivery.

OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and in fetal cord blood at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, Illinois, USA), with p<0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking and in fetal blood by cord blood analysis at delivery. Cord pH was also recorded. RESULTS: There was no significant correlation between maternal IGF-1, IGF-2, or IGFBP-3 levels and fetal acidosis. However, a significant correlation does exist between cord IGF-1 levels and fetal acidosis. CONCLUSION: Fetal cord IGF-1 has a significant correlation with fetal acidosis at delivery.