Etaoin Kent

Placental cord insertion and birthweight discordance in twin pregnancies: results of the national prospective ESPRiT Study

OBJECTIVE The purpose of this study was to evaluate the impact of noncentral placental cord insertion on birthweight discordance in twins. STUDY DESIGN We performed a multicenter, prospective trial of twin pregnancies. Placental cord insertion was documented as central, marginal, or velamentous according to a defined protocol. Association of the placental cord insertion site with chorionicity, birthweight discordance, and growth restriction were assessed. RESULTS Eight hundred sixteen twin pairs were evaluated; 165 pairs were monochorionic, and 651 pairs were dichorionic. Monochorionic twins had higher rates of marginal (P = .0068) and velamentous (P < .0001) placental cord insertion. Noncentral placental cord insertion was more frequent in smaller twins of discordant pairs than control pairs (29.8% vs 19.1%; P = .004). Velamentous placental cord insertion in monochorionic twins was associated significantly with birthweight discordance (odds ratio, 3.5; 95% confidence interval, 1.3-9.4) and growth restriction (odds ratio, 4; 95% confidence interval, 1.1-14.3). CONCLUSION Noncentral placental cord insertion contributes to birthweight discordance in monochorionic twin pregnancies. Sonographic delineation of placental cord insertion may be of value in antenatal assessment of twin pregnancies.

Placental pathology, birthweight discordance, and growth restriction in twin pregnancy: results of the ESPRiT Study.

OBJECTIVE We sought to evaluate the association between placental histological abnormalities and birthweight discordance and growth restriction in twin pregnancies. STUDY DESIGN We performed a multicenter, prospective study of twin pregnancies. Placentas were examined for evidence of infarction, retroplacental hemorrhage, chorangioma, subchorial fibrin, or abnormal villus maturation. Association of placental lesions with chorionicity, birthweight discordance, and growth restriction were assessed. RESULTS In all, 668 twin pairs were studied, 21.1% monochorionic and 78.9% dichorionic. Histological abnormalities were more frequent in placentas of smaller twins of birthweight discordant pairs (P = .02) and in placentas of small for gestational age infants (P = .0001) when compared to controls. The association of placental abnormalities with both birthweight discordance and small for gestational age was significant for dichorionic twins (P = .01 and .0001, respectively). No such association was seen in monochorionic twins. CONCLUSION In a large, prospective, multicenter study, we observed a strong relationship between abnormalities of placental histology and birthweight discordance and growth restriction in dichorionic, but not monochorionic, twin pregnancies.

Platelet reactivity and pregnancy loss

OBJECTIVE We sought to critically evaluate platelet function in recurrent miscarriage (RM). STUDY DESIGN We conducted a prospective study comparing 30 patients with unexplained recurrent first-trimester pregnancy loss with 30 control subjects matched for age and serum progesterone level. Platelet function was determined using a modified assay of light transmission aggregometry with multiple agonists at different concentrations. Dose-response curves were created and half-maximal effective concentration values were calculated. RESULTS At test completion the half-maximal effective concentration values for arachidonic acid in the patients with RM were significantly less than in the control subjects (0.153 vs 0.230; P = .0099). The dose-response curves were tightly matched for the other agonists. CONCLUSION This novel measurement of platelet function has demonstrated that patients with unexplained RM have significantly increased platelet aggregation in response to arachidonic acid. The enhanced response to this agonist provides an empirical rationale for the use of aspirin in management of this clinical condition.

Outcome following selective fetoscopic laser ablation for twin to twin transfusion syndrome: an 8 year national collaborative experience

OBJECTIVE With the recognition of the role of fetoscopic laser ablation for twin to twin transfusion syndrome (TTTS), there is a requirement for auditable standards for this technically challenging and specialized treatment. The purpose of this study is to report on the perinatal and medium-term neurodevelopmental outcomes following an 8-year national single center experience in the management of TTTS using the selective fetoscopic laser ablation technique. STUDY DESIGN An audit of all cases of TTTS treated with selective laser ablation by a single national fetal medicine team was performed. Overall perinatal survival and medium-term neurodevelopmental outcomes were reported and correlated with gestational age at diagnosis, placental location, volume of amnio-reduction, Quintero staging and percentage inter-twin growth discordance. Procedure-related complications were recorded. RESULTS The overall fetal survival for the first 105 consecutive cases of TTTS was 61% (128/210 fetuses). Dual survival occurred in 47% (49/105) of cases, and with a single survival rate of 28% (30/105), perinatal survival of least one infant was achieved in 75% (79/105) of cases. No correlation was found between any clinical or sonographic marker and perinatal outcome, although dual survival was noted to be significantly decreased with increasing Quintero stage (p=0.041). Currently, 86% of survivors have been reported to have a normal medium-term neurological outcome. CONCLUSION Fetoscopic laser ablation is the established optimal treatment for severe twin to twin transfusion syndrome (TTTS). We report comparable short and medium-term outcomes following the selective fetoscopic technique comparing results from our national program with internationally published single-center outcomes, supporting the efficacy and safety of this treatment at our center.

Endothelial Progenitor Cells in Mothers of Low-Birthweight Infants: A Link between Defective Placental Vascularization and Increased Cardiovascular Risk?

CONTEXT Offspring birthweight is inversely associated with future maternal cardiovascular mortality, a relationship that has yet to be fully elucidated. Endothelial progenitor cells (EPCs) are thought to play a key role in vasculogenesis, and EPC numbers reflect cardiovascular risk. OBJECTIVE Our objective was to ascertain whether EPC number or function was reduced in mothers of low-birthweight infants. DESIGN AND SETTING This was a prospective cohort study in a general antenatal department of a university maternity hospital. PARTICIPANTS Twenty-three mothers of small for gestational age (SGA) infants (birthweight < 10th centile) and 23 mothers of appropriate for gestational age (AGA) infants (birthweight ≥ 10th centile) were recruited. MAIN OUTCOME MEASURES Maternal EPC number and function, conventional cardiovascular risk markers, and cord blood adiponectin were measured. RESULTS Median EPC count was lower (294 vs. 367, P = 0.005) and EPC migration was reduced (0.91 vs. 1.59, P < 0.001) in SGA compared with AGA infants, with no difference in EPC adhesion (0.221 vs. 0.284 fluorescence units, P = 0.257). Maternal triglyceride levels were higher in SGA than AGA infants (0.98 vs. 0.78 mmol/liter, P = 0.006), but there was no difference in cholesterol, glucose, insulin, glycosylated hemoglobin, adiponectin, or blood pressure. There was a moderate monotone (increasing) relationship between birthweight and umbilical cord blood adiponectin (r = 0.475, P = 0.005). CONCLUSION Giving birth to an SGA infant was associated with lower maternal EPC number and reduced migratory function. Cord blood adiponectin was significantly correlated with birthweight.

Early and late preterm delivery rates - a comparison of differing tocolytic policies in a single urban population.

Objective: Preterm delivery results in neonatal morbidity and mortality. We set out to estimate the difference in rates of preterm delivery in two institutions, serving a single population, with differing policies regarding use of tocolytic drugs for the prevention of preterm delivery. Study design: A retrospective study comparing preterm delivery rates between 2002 and 2007 in two large tertiary hospitals serving a single urban population with similar risk factor profile located less than 2 miles from each other. During the study period Hospital A routinely used tocolytic therapy, Hospital B operates a policy of never using any tocolytic drugs. Rates of delivery prior to 26, 30, 34 and 37 weeks were compared for each hospital. Results: During the study period there were 90,843 deliveries between the two hospitals. The overall rates of preterm delivery at less than 37 weeks gestation were comparable with 6.62% (2794/42,232) in Hospital A and 6.15% (2989/48,611) in Hospital B (p = 0.99). There was no significant difference in the numbers delivering at less than 34 weeks, 995/42,232 (2.36%) versus 1134/48,611 (2.33%), p = 0.59, less than 30 weeks, 403/42,232 (0.95%) versus 429/48,611 (0.88%), p = 0.87 or prior to 26 weeks, 126/42,232 (0.29%) versus 121/48,611 (0.25%), p= 0.08. Conclusion: In this large population routine use of tocolytic drugs in the treatment of threatened preterm labor does not alter rates of early or late preterm delivery. While this study is limited by its retrospective nature, it calls into question the practice of tocolysis.

Infants Born with Down Syndrome: Burden of Disease in the Early Neonatal Period

Objective To evaluate the incidence of direct admission of infants with Down syndrome to the postnatal ward (well newborn nursery) vs the neonatal intensive care unit (NICU), and to describe the incidence of congenital heart disease (CHD) and pulmonary hypertension (PH). Study design This retrospective cohort study of Down syndrome used the maternal/infant database (2011‐2016) at the Rotunda Hospital in Dublin, Ireland. Admission location, early neonatal morbidities, outcomes, and duration of stay were evaluated and regression analyses were conducted to identify risk factors associated with morbidity and mortality. Results Of the 121 infants with Down syndrome, 54 (45%) were initially admitted to the postnatal ward, but 38 (70%) were later admitted to the NICU. Low oxygen saturation profile was the most common cause for the initial and subsequent admission to the NICU. Sixty‐six percent of the infants (80/121) had CHD, 34% (41/121) had PH, and 6% died. Risk factors independently associated with primary NICU admission included antenatal diagnosis of Down syndrome, presence of CHD, PH, and the need for ventilation. Conclusions Infants with Down syndrome initially admitted to the postnatal ward have a high likelihood of requiring NICU admission. Overall, high rates of neonatal morbidity were noted, including rates of PH that were higher than previously reported. Proper screening of all infants with Down syndrome for CHD and PH is recommended to facilitate timely diagnoses and potentially shorten the duration of the hospital stay.

The Impact of Maternal Gestational Hypertension and the Use of Anti-Hypertensives on Neonatal Myocardial Performance

Background: Assessment of myocardial performance in neonates using advanced techniques such as deformation imaging and rotational mechanics has gained considerable interest. The applicability of these techniques for elucidating abnormal myocardial performance in various clinical scenarios is becoming established. We hypothesise that term infants born to mothers with gestational hypertension (GH) may experience impaired performance of the left and right ventricles during the early neonatal period. Objectives: We aimed to assess left and right ventricular (LV and RV) function using echocardiography in infants born to mothers with GH and compare them to a control group. Methods: Term infants (>36+6 weeks) born to mothers with GH underwent assessment to measure biventricular function using ejection fraction (EF), deformation imaging, left-ventricle rotational mechanics (apical rotation, basal rotation, twist, twist rate, and untwist rate), and right ventricle-specific functional parameters (tricuspid annular plane systolic excursion and fractional area change) in the first 48 h after birth. A control group comprising infants born to healthy mothers was used for comparison. Results: Fifteen infants with maternal GH and 30 age-matched controls were enrolled. The GH infants exhibited no differences in birthweight or LV or RV length, but they had lower EF (54 vs. 61%; p < 0.01), LV global longitudinal strain (-20 vs. -25%; p < 0.01), and LV twist (11 vs. 16°; p = 0.04). There were no differences in any of the RV functional parameters. Conclusion: Infants born to mothers with GH exhibited lower LV function than healthy controls, while RV function appeared to be preserved. This relationship warrants further exploration in a larger cohort.

Reply to letter to the editor entitled “Non-Invasive cardiac output monitoring (NICOM ® ) can predict the evolution of uteroplacental disease—results of the prospective HANDLE study”

We thank Dr. Perry et al. [1] for their recent interest in the HANDLE study and would like to respond to some of their comments relating to our recent publication on the role of bioreactance obtained haemodynamic variables in the prediction of the uteroplacental diseases preeclampsia (PE) and fetal growth restriction (FGR) [2]. Our cohort did not exclude those with advanced maternal age (range 16–44 years) or obesity (body mass index range 16.26– 39.89; n = 54 (14.8%) with a BMI >30). This technology has previously been applied by my co-authors to a high risk population with a history of PE [3]. Therefore, our objective for this cohort was to better identify the at risk nulliparous parturient. As such multiparous women and those with a history of PE were excluded. In our methodology we detailed the power calculation from an anticipated 5% nulliparous PE rate in our local population and recruited 422 expecting to capture 20 PE cases. The anticipated 5% and subsequent 20 cases of nulliparous PE rate was previously achieved in another study carried out in our unit using transthoracic echocardiography in low risk nulliparous women [4]. Our group have also recently demonstrated very acceptable agreement between bioreactance and echocardiography for the measurement of stoke volume (mean bias 6 mL, LOA 18–29 mL, ICC 0.8) and measurement of cardiac output (mean bias 0.2L, LOA 1.3–1.7L, ICC 0.8) this cohort with a mean percentage error of 26% and a precision of 3.4% [5]. We entirely agree that FGR is not diagnosed by an EFW of <10th centile. It is well established that the detection rate fetal growth restriction (FGR) via clinical examination is suboptimal [6]. The authors completely agree that those fetus at greatest risk are those for whom the estimated fetal weight is less than the third centile. However, even when a definition of a birthweight <10th centile is applied there is a significant differencce in the haemodynamic status of the mother which therefore poses a potential for earlier recognition and better management of those pregnancies. As detailed in the manuscript only one third of infants with a birthweight <10th centile were suspected antenatally in this cohort. Although the data was not presented in the referred manuscript there were no differences in the haemodynamics of pregnancies where the birthweight was <3rd centile and those <10th centile. Whilst Perry et al. suggest a smaller mother would have a lower cardiac output we did not observe this difference. There was no difference in maternal cardiac index (adjusted for body surface area) of FGR and unaffected pregnancies. We thank Dr Perry et al. for their acknowledgement surrounding the strength of the postnatal element of this study. This has not been addressed in this manuscript and the postnatal persistence of a high resistance vasculature is the subject of a further manuscript which is currently under submission.

2.2 Abnormal cerebroplacental ratio predicts adverse outcomes in dichorionic twins

Objective To evaluate the significance of an abnormal cerebroplacental ratio (CPR) in twin pregnancies. Study design In the prospective multicenter ESPRiT study, twin pregnancies underwent serial sonographic evaluation including multi-vessel Doppler studies. CPR was expressed as the ratio of the pulsatility index (PI) of the middle cerebral artery to the PI of the umbilical artery. CPR PI < 1.0 was considered abnormal. The relationship between abnormal CPR at final sonographic examination and adverse clinical outcomes was assessed and results stratified by chorionicity. A p-value of <0.01 was considered significant. Results Of 1028 twin pairs recruited, 932 had CPR data available. 18% of the cohort were monochorionic (MC), of whom 15.2% had an abnormal CPR at the final sonographic evaluation. This was not significantly different among dichorionic (DC) twins (12.7%; p = 0.24 for comparison). In MC twins an abnormal CPR did not predict adverse clinical outcomes. In contrast, among DC twins an abnormal CPR prior to delivery was associated with reduced mean birthweight (BW) (p = 0.0002) and an increase in the rates of BW <5th centile (p = 0.01), NICU admission (p = 0.001) and perinatal morbidity (p = 0.002). There was also a trend toward a lower mean GA at delivery and higher rates of both preterm delivery and significant inter-twin BW discordance. Conclusion An abnormal CPR is strongly associated with adverse outcomes in DC twin pregnancies but not in MC twin pregnancies. This reflects the differing pathological processes, which affect growth and placental function in DC and MC pregnancies.