Volume 44, Issue 8 - Highlight: Multiples

Objective: This prospective cohort study evaluated the relationship between fertility treatments and the prevalence and outcomes of dichorionic discordant twins. This issue has gained importance due to twin gestations resulting from fertility treatments. Study design: Mothers of dichorionic twin pregnancies achieved in a single fertility clinic by assisted reproduction techniques, who had completed the first trimester of the pregnancy, were prospectively enrolled. Pregnancies with major fetal anomalies were excluded. Data regarding concordant and discordant twins based on the fertility treatments given to achieve the pregnancies were analyzed to determine the prevalence of discordance and pregnancy outcomes. Results: A total of 571 dichorionic twin pregnancies were available for evaluation. Fertility treatments modalities, sperm quality and implantation of cultured and thawed embryos did not influence the rate and severity of discordant twins. Increased hospitalization rates were found among discordant (n=108) compared to concordant (n=463) twins (47.2% vs. 31.3%, P<0.0001) and higher rates of betamethasone treatment (65.7% vs. 28.9%, P<0.0001). Secondary analysis of discordant pregnancies with a growth restricted twin, revealed the same results. We found no association between various fertility treatments and twin discordance. Conclusions: Our data suggest that fertility treatments do not play a major role in the pervasiveness and outcome of discordant twin pregnancies.

Aim: In the current review study, we present recent data regarding the importance of intertwin estimated fetal weight (EFW) and crown rump length (CRL) discordance for the prediction of adverse perinatal outcome both in monochorionic and in dichorionic diamniotic gestations. Results: Twins with significant weight disparity are associated with higher rates of perinatal morbidity and mortality, regardless of gestational age at delivery. However, there is no agreement regarding as to the cut off value above which the perinatal outcome is unfavorably affected and the threshold range from 10 to 30%. On the other hand, CRL discrepancy has proved to be a weak predictor of adverse outcomes, such as fetal or neonatal death in fetuses without chromosomal and structural abnormalities. In clinical practice, decisions about obstetric surveillance of discordant twin gestations, frequency of fetal sonographic monitoring and time of delivery are usually based on amniotic fluid volume and Doppler assessments on a weekly basis. Conclusion: Significant EFW discordance leads to adverse perinatal outcome, although the cut-off value has not yet been estimated. CRL discrepancy is not correlated well with adverse perinatal outcome. However, increased monitoring of women with EFW and CRL discrepancy is suggested.

Objective: To calculate an updated prospective risk of fetal death in monochorionic-biamniotic (MCBA) twins. Study design: We evaluated 520 MCBA twin pregnancies that had intensive prenatal surveillance and delivered in a single Portuguese referral center. The prospective risk of fetal death was calculated as the total number of deaths at the beginning of the gestational period divided by the number of continuing pregnancies at or beyond that period. Data were compared to the 2006 previous report. Results: Nearly 80% of the neonates weighed <2500 g, including 13.5% who weighed <1500 g. Half were born at <36 weeks, including 13.8% who were born at <32 weeks. The data indicate an increased IUFD rate over time – 16 fetal deaths per pregnancy (3.1%) and 22 IUFDs per fetus (2.1%). The rate of IUFD after 32–33 weeks, however, was halved (1/187 pregnancies and 1/365 fetuses, 0.5 and 0.3%, respectively). Conclusion: Intensive prenatal surveillance might decrease the unexpected fetal death rates after 33 week’s gestation and our data do not support elective preterm birth for uncomplicated MCBA twins.

Objective: To evaluate if the perinatal outcomes of dichorionic-triamniotic (DC) triplets are significantly different than that of trichorionic (TC) triplets. Study design: Comparison of maternal and neonatal data of 44 DC to 46 TC triplets, using univariate analysis. Results: DC triplets were significantly more common after spontaneous conception but all other maternal characteristics as well complications and cesarean section rates were similar. Both groups had similar incidence of birth at <32 and <28 weeks as well as similar incidence of very low and extremely low birth weight. There was similar incidence of neonatal morbidity except for twin-twin transfusion syndrome (13.6%) in the DC group. The stillbirth rate was 45/1000 and 29/1000, the early neonatal mortality rates were 63/1000 and 45/1000, and the perinatal mortality rate was 106/1000 and 72/1000 for DC and TC triplets, respectively (all not significantly different). Conclusions: Our data indicate that DC twins are not significantly disadvantaged compared to TC triplets and the similar outcomes might be reassuring for those who consider continuing their DC triplet pregnancy.

Objecive: To evaluate the perinatal outcome of monochorionic-diamniotic twins conceived by assisted reproduction technology (ART). Methods: We compared data from a national population-based perinatal registry on perinatal outcomes of monochorionic-diamniotic twins conceived by ART with their dichorionic counterparts and with spontaneous monochorionic-diamniotic twins. We compared maternal characteristics, pregnancy complications and perinatal outcomes. Results: Monochorionic-diamniotic twin pregnancies (n=45) comprised 5.5% of all ART twins, and 9.3% of all monochorionic twins in this dataset. ART does not appear to increase the already high risk of monochorionicity compared to spontaneous conception, with the latter having an increased incidence for birth weight <1500 g [odds ratio (OD) 2.6, 95% confidence interval (CI) 1.2–5.4]. Conclusion: Our results disagree with hospital-based data and suggest that monochorionic-diamniotic twins following ART are not at increased risk of adverse perinatal outcomes compared to spontaneous monochorionic-diamniotic twins as well as to dichorionc twins conceived by ART.

Objective: To compare indications for delivery and neonatal morbidities between twins and singletons born between 34 and 35 weeks of gestation. Study design: A prospective observational study was performed in which all infants born between January and August 2008, at Sheba Medical Center at 34 0/7–35 6/7 weeks of gestational age were included. Indications for delivery, infants’ morbidities and medical interventions were documented. Twins and singletons were compared for antenatal maternal characteristics, risks of short-term neonatal complications and interventions. Results: One hundred and seventy-three mothers and 229 neonates (114 twins and 115 singletons) were included. Background maternal characteristics as well as the use of antenatal steroids and MgSO4 were similar between the groups. Only 44% of all deliveries were spontaneous, while the rest were indicated deliveries. Twins were born lighter and 31.9% of them were SGA. Nevertheless, singletons were significantly more likely to receive medical interventions such as prolonged oxygen use (>1 day) and phototherapy. All late preterm infants (n=5) needing surfactant administration were singletons. Overall, the risk of needing any medical intervention was significantly higher for singletons compared with twins (OR 1.8, 95% CI 1.02–3.2). Conclusions: A significant proportion of late preterm births is iatrogenic. Twins and singletons are dissimilar with regards to risks of short-term complications. Despite being born smaller and more SGA, twins are at lower risk of requiring medical intervention in the immediate neonatal period compared with singletons.

Background: Data regarding the effects of multifetal pregnancy on the incidence of gestational diabetes mellitus (GDM) are inconsistent and even conflicting. Twin pregnancies have been associated with no increase, a marginal increase or a higher incidence of gestational diabetes. In triplet pregnancies, these effects have not been investigated yet. Objectives: To analyze the results of the glucose challenge and tolerance tests in singleton, twin and triplet pregnancies. Study design: A retrospective database analysis of pregnant women with singletons, twins or triplets who had complete results of the 50 g glucose challenge test (GCT) and the 100 g oral glucose tolerance test (OGTT). The cohort included 12,382 singletons, 515 twins and 39 triplets. Results: There were significantly higher rates of abnormal GCTs in twins and triplets compared to singletons (45.4% and 33.3%, respectively vs. 13.7%, P<0.001 and P<0.05). Significantly higher rates of gestational diabetes in twins (10.1% vs. 2.9 %, P<0.001) and triplets (12.8% vs. 2.9%, P<0.05) compared to singletons were observed. Mean glucose levels after the GCT were higher in twins compared to singletons, and even more in triplets (108 mg/dL in singletons vs. 120 mg/dL in twins vs. 129 mg/dL in triplets, P<0.001). Conclusions: Glucose intolerance is aggravated in multifetal pregnancies. The likelihood of an abnormal GCT and gestational diabetes is higher in twins and triplets compared to singletons.

Objective: To evaluate the relationship between respiratory morbidity in twins by gestational age, birth order and mode of delivery. Methods: All twin deliveries at <37 weeks, registered in a national database, in the period 2003–2012 were classified into four gestational age groups: 33–36, 30–32, 28–29, and <28 weeks. Outcome variables included transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS) and need for assisted ventilation. Results: A total of 1836 twins were born vaginally, and 2142 twins were born by cesarean delivery, for a grand total of 3978 twins. TTN did not appear to be related to birth order and to the mode of delivery. In contrast, RDS was more frequent among the second born twins in the vaginal birth groups born at 30–36 weeks [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.2–5.1 and OR 2.0, 95% CI 1.2–3.5 for 33–36 weeks and 30–32 weeks, respectively], whereas this trend was seen in the cesarean birth groups born earlier (OR 3.8, 95% CI 1.1–13.0 for 28–29 weeks). Cesarean delivery significantly increased the frequency of RDS in twin A as well as in twin B compared with vaginal birth, but only at gestational ages <30 weeks. Conclusion: Mode of delivery and birth order have a gestational age dependent effect on the incidence of RDS.

Objective: To investigate the neonatal outcomes of twin pregnancies delivered at late-preterm versus term gestation based on chorionicity and indication for delivery. Study Design: This is a retrospective cohort study of women with twin pregnancies delivered at ≥34 weeks of gestation from 1995 to 2014. Subjects were categorized into two groups according to gestational age at delivery: late-preterm group (34–36 weeks) and term group (≥37 weeks). Neonatal outcome measures including neonatal intensive care unit (NICU) admission, mechanical ventilator support, and respiratory distress syndrome (RDS) were compared between the late-preterm and term group based on chorionicity (monochorionic or dichorionic) and delivery indication (elective or non-elective). Results: A total of 1198 twin pregnancies were included in the study: 679 in the late-preterm group and 519 in the term group. Late-preterm twin infants had higher rates of NICU admission, mechanical ventilator support, and RDS than did term twin infants, regardless of the chorionicity and indication for delivery. In the multivariable analysis, late-preterm birth, monochorionicity, and non-elective delivery were independently associated with a significantly higher risk of NICU admission and mechanical ventilator support. Conclusion: The late-preterm birth was associated with a higher risk of adverse neonatal outcome regardless of chorionicity and indication for delivery, and showed significantly increased risk by monochorionicity and non-elective delivery.

Objective: Though the outcome for children with congenital diaphragmal hernia (CDH) is improving, management of seriously compromised respiratory and cardiovascular function remains a great challenge. The aim of this study was to review a tertiary center experience in treating children with CDH. Design: Retrospective observational study from January 2005 to December 2014. Setting: Neonatal Intensive Care Unit (NICU) of University Children Hospital (UCH), Belgrade, Serbia. Patients: Children with CDH. Results: The CDH was diagnosed prenatally in 23% patients. An overall survival rate was 62%. Among those patients who underwent surgical repair 29 (90%) survived. There was statistically significant difference in survival rate between operated patients and total examined population (P=0.020). Prenatally diagnosed neonates with CDH had significantly lower survival rate comparing to those who were postnatally diagnosed (20% vs. 75%; P=0.002). Fatal outcome was more frequent in patients with small birth weight comparing to those with normal birth weight (67% vs. 30%; P=0.046). Conclusions: Our center survival rate for CDH is in accordance with other reported studies. Based on our experience there are potential points for further improvement. First, further increase of prenatal detection, planning for delivery, and coordinated transfer to tertiary institution, in order to avoid transfer of near death patients. Second, preoperative management in the NICU. This could be done by more uniform implementation of current consensual guidelines in monitoring, mechanical ventilation and circulatory support of these delicate patients, together with rationale use of newer therapeutic resources.

Aim: To evaluate the short-term effects of blood transfusion on iron status [hemoglobin, ferritin, soluble transferrin receptor (sTfR), and reticulocyte count], hepcidin, and erythropoietin in stable preterm infants. Method: Sixty-three preterm infants treated with red blood cell transfusions (RBCTs) were included. Venous blood samples were collected before and within 24 h after each transfusion. Results: Hemoglobin concentration increased after RBCT (7.2±1.2 g/dL vs. 13.7±2.3 g/dL, P=0.02), as well as ferritin [131 (63–110.4) ng/mL vs. 211 (125.7–299.2) ng/mL, P=0.05); reticulocyte count decreased. sTfR did not change. Hepcidin serum levels increased from 37.5 (21.3–84.7) ng/mL to 72.6 (31.3–126.2) ng/mL, (P=0.04) and erythropoietin decreased (48±19 pg/mL vs. 29±17 pg/mL, P=0.06) after RBCT. A positive linear correlation was found (R 2 =0.76, P=0.0001) between hepcidin and ferritin levels of post-minus-pre RBCT. Hepcidin levels increased significantly in preterm infants who received RBCT after 1 month of age compared to those who received RBCT at <1 month (P=0.03). No correlation was found between gestational age, weight appropriate for age, or length of blood storage and hepcidin levels. Conclusion: Preterm infants can control iron levels by regulating hepcidin and decreasing erythropoietin. This ability varies with postnatal age.

Objectives: We investigated the accuracy of left-to-right shunt detection using transpulmonary ultrasound dilution (TPUD) and compared the agreement between pulmonary over systemic blood flow (Qp/Qs) ratio measured by TPUD [Qp/Qs(tpud)] and ultrasonic flow probes [Qp/Qs(ufp)]. Methods: Seven newborn lambs under general anesthesia were connected to the TPUD monitor (COstatus™) after insertion of arterial and central venous catheters. A Gore-Tex ® shunt, inserted between the descending aorta and left pulmonary artery, was intermittently opened and closed while cardiac output was varied by blood withdrawals. Flow probes were placed around the main pulmonary artery (Qufp) and the descending aorta proximal (Qpre) and distal (Qpost) to the shunt insertion. Qp/Qs(ufp) was calculated as (Qufp+Qpre–Qpost)/Qufp. Results: Seventy-two paired measurement sessions were analyzed. Shunts were detected by TPUD with a positive predictive value of 86%, a negative predictive value of 100%, a sensitivity of 100% and a specificity of 83%. The Bland-Altman analysis comparing Qp/Qs(tpud) and Qp/Qs(ufp) showed an overall mean bias (SD) of 0.1 (0.3), limits of agreement (LOA) of ±0.6 and a percentage error of 34.8%. Conclusions: The qualitative diagnostic accuracy of TPUD for shunt detection is high. Modification of the algorithm seems required as shunt quantification by TPUD is accurate, but not yet very precise.

Objective: This is a comprehensive study designed to evaluate the clinical usefulness of transcutaneous bilirubinometry (TcB) in very low birth weight (VLBW) newborns of African American (AA) descent. Methods: TcB was conducted at the anterior superior iliac spine (ASIS), temporal region and sternum within 2 h of total serum bilirubin (TSB) measurements in newborns born at ≤32 weeks’ gestation prospectively. Average (AVG) TcB levels were also calculated. The relationships between TSB and TcB levels were analyzed using non-parametric Spearman bivariate correlations, a Bland-Altman plot procedure and a decision tree (DT) analysis. Results: One hundred newborns and 555 TSB data points were available. Eighty-nine percent of the newborns were AA. A significant correlation (P<0.0001) was observed between TSB and TcB values obtained at the ASIS (r=0.73), sternum (0.73), temporal region (0.61) and AVG (0.77). The Bland-Altman plot revealed a good agreement between AVG TcB values and TSB values. A DT analysis indicated that AVG TcB was also found to be the most significant predictor of TSB values in both the no phototherapy (PT) and biliblanket subgroups. Conclusion: TcB can be used reliably in VLBW AA newborns in the absence of overhead PT. The use of TcB in monitoring jaundice in VLBW newborns would help decrease the number of blood draws and cost of care.

Objective: To examine the outcomes of births among small and appropriate for gestational age (SGA and AGA) infants by gestational age and maternal characteristics. Materials and methods: We used a national perinatal registry to compare the selected maternal and neonatal outcomes between AGA and SGA neonates born at gestational age groups 33–36, 30–32, 28–29, and <28 weeks. We evaluated maternal body mass index (BMI), pre-gestational/gestational diabetes, hypertensive disorders, and cesarean births as well as frequencies of 5-min Apgar score <7, intraventricular hemorrhage (IVH), respiratory distress syndrome (RDS), the need for assisted ventilation, and early neonatal deaths. Results: We evaluated 159,774 AGA (8871 preterm) and 13,735 SGA (1147 preterm) infants and found a gradual decrease in the incidence of SGA infants with increasing gestational age. Diabetes was unrelated to having an SGA or AGA infant among preterm births, but the odds ratio (OR) for preeclampsia among preterm-SGA pregnancies was up to 6.9 (95% CI 3.8, 12.5) at <28 weeks. SGA infants fare worse compared to AGA neonates in every parameter tested but only in preterm births >30 weeks. Conclusions: Being SGA further complicates preterm births after 30 weeks of gestation but not earlier. This might suggest that an extended period in the hostile intrauterine environment, or that being born at <30 weeks, is bad enough and is not further aggravated by being SGA.