Volume 46, Issue 7 - Highlight: Antenatal Care

The identification of congenital birth defects and fetal malformations continues to increase during the antenatal period with improved imaging techniques. Understanding of how to treat specific fetal conditions continues to improve outcomes from these treatment modalities. In an effort to further improvement in this field, we provide a review that begins with a brief background of fetal surgery including the history of fetal surgery, ethics surrounding fetal surgery, and considerations of how to treat the fetus during intervention. A synopsis of the most commonly encountered disease processes treated by fetal intervention/surgery including definitions, treatment modalities, and outcomes following fetal intervention/surgery is then provided. Within the sections describing each disease process, methodology is described that has helped with efficiency and success of procedures performed at our institution.

In recent years, the idea of the inverted pyramid of prenatal care and monitoring has emerged, for the purpose of prediction and prevention, early detection and treatment of health disorders of the fetus. Is this enough? If we analyze the period behind us, progress has been made in the field of detection of multiple pregnancies, dating of pregnancy and prenatal detection of chromosomal and structural fetal disorders, as well as a small amount of progress in terms of prediction and prevention of preeclampsia. If these disorders are the consequence of the disturbed or dysfunctional placentation, they are rooted at the time of implantation. This means that the changes that lead to the dysfunctional implantation should be sought in the pre-implantation period, in relation between the embryo and the endometrium. An extended inverted pyramid is necessary to find better results in perinatal medicine. This means that the interventions should be focused on the preconception and peri-implantation periods. The therapy should be on the subcellular and genetic level by applying the latest biotechnological procedures. It is possible that the time is approaching when the listed disorders of a pregnancy will be the indications for the application of a non stimulated in-vitro fertilization (IVF) (without ovary stimulating medication) with the use of new biotechnological achievements.

Fetal malformations are more frequent in twins than in singletons. The aim of our study was to define the influence of a malformed twin on di-chorionic pregnancy outcomes. We performed a retrospective cohort study of di-chorionic pregnancies delivered between 2000 and 2015. Exclusion criteria were: both twins affected by fetal malformations, double intra-uterine fetal death in pregnancies without fetal malformation, selective feticide and therapeutic pregnancy termination. We compared maternal and fetal outcomes of di-chorionic pregnancies not complicated by fetal malformations with pregnancies affected by a single malformed fetus with conservative management. We included 642 di-chorionic pregnancies: 56 (case group, 8.7%) with one twin affected by a malformation (20 minor, 36 major ones), 586 (control group, 91.3%) without fetal malformation. No differences were found on maternal and not malformed co-twin outcomes when compared to pregnancies with no malformation; case vs control group presented similar rates of preeclampsia (8.9% vs. 10.8%, respectively), intrauterine growth restriction (7.1% vs. 9.4%) and composite adverse neonatal outcomes (19.6% vs. 15.1%). No case of fetal death in not malformed co-twin was reported. Expectant management could be a safe option for both mother and co-twin in case of di-chorionic twin pregnancy complicated by only one malformed fetus.

Background: Different etiologies for recurrent pregnancy loss have been identified, among them are: anatomical, endocrine, genetic, chromosomal and thrombophilia pathologies. Aims: To assess medical and obstetric characteristics, and pregnancy outcomes, among women with uterine abnormalities and recurrent pregnancy loss (RPL). This study also aims to assess the impact of uterine anatomic surgical correction on pregnancy outcomes. Methods: A retrospective case control study of 313 patients with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy. Anatomic abnormalities were detected in 80 patients. All patients were evaluated and treated in the RPL clinic at Soroka University Medical Center. Out of 80 patients with uterine anatomic abnormalities, 19 underwent surgical correction, 32 did not and 29 had no clear record of surgical intervention, and thus were excluded from this study. Results: Women with anatomic abnormalities had a higher rate of previous cesarean section (18.8% vs. 8.6%, P=0.022), tended to have a lower number of previous live births (1.05 vs. 1.37, P=0.07), and a higher rate of preterm delivery (22.9% vs. 10%, P=0.037). Using multivariate logistic regression analysis, anatomic abnormality was identified as an independent risk factor for RPL in patients with previous cesarean section after controlling for place of residence, positive genetic/autoimmune/endocrine workup, and fertility problems (OR 7.22; 95% CI 1.17–44.54, P=0.03). Women suffering from anatomic abnormalities tended to have a higher rate of pregnancy loss compared to those without anatomic abnormalities (40% vs. 30.9%, P=0.2). The difference in pregnancy loss rate among women who underwent surgical correction compared to those who did not was not statistically significant. Conclusion: In patients with previous cesarean section, uterine abnormality is an independent risk factor for pregnancy loss. Surgical correction of uterine abnormalities among RPL patients might have the potential to improve live birth rate.

Objective: Echocardiography is the most important tool to assess infants with congenital diaphragmatic hernia (CDH) for pulmonary hypertension (PH). The pattern of blood flow in the pulmonary artery [described as time to peak velocity (TPV)/right ventricular ejection time (RVET) ratio] provides distinct information about pulmonary arterial pressure. The aim of our study was to investigate the correlation of TPV/RVET measurements with the most commonly used classification system for PH in CDH newborns and the association of these measurements with outcome parameters. Methods: Echocardiographic measurements were obtained in 40 CDH newborns within 6 h of life. The obtained measurements were correlated with the decision for or against extracorporeal membrane oxygenation (ECMO); early mortality; total duration of mechanical ventilation and total duration of oxygen supplementation. Results: The correlation coefficient between severity of PH and TPV/RVET measurements was −0.696 (P<0.001). Using receiver operating characteristic (ROC) analyses the optimal cutoff for TPV/RVET in order to predict the necessity for ECMO or early mortality without ECMO was 0.29 with a sensitivity of 86.7%, a specificity of 68%, a positive predictive value of 61.9% and a negative predictive value of 89.5%. Newborns with a TPV/RVET below the cutoff had a 5.9-fold risk for ECMO or early mortality, a significantly longer duration of mechanical ventilation (13.4 days vs. 7.4 days, P=0.003) and oxygen supplementation (22.4 days vs. 9.0 days, P=0.019), and a lower survival rate (76.2% vs. 100%, P=0.021). Conclusions: TPV/RVET is a feasible parameter to assess PH in CDH newborns with close correlation to outcome parameters.

Introduction: To evaluate various sonographic estimated fetal weight (sEFW) formulas’ accuracy for small- and large-for-gestational age (SGA/LGA) prediction in breech-presenting fetuses. Materials and methods: A retrospective analysis of all ultrasound-based fetal biometrical measurements performed within 3 days of delivery in term pregnancies, in one medical center (2007–2014). Overall, 274 breech-presenting fetuses (study group) were compared to 274 vertex-presenting fetuses (control group) matched by gender, gestational age and birth weight. sEFW was calculated by six previously published formulas. Accuracy was compared utilizing systematic error and random error for every formula. Prediction precision of SGA and LGA was evaluated by calculating each formula’s sensitivity, specificity, +/− predictive value, and the area under the receiver-operating characteristic (ROC) curve (AUC). Results: Systematic error and random error varied greatly between formulas, ranging from −7.4% to 3.1%, 7.3% to 8.3% for the vertex-presenting fetuses and −8.9% to 1.9%, 7.9% to 8.6% for the breech-presenting fetuses, respectively. There was no statistical difference in small- or large-for-gestational age prediction parameters between the groups. The highest sensitivity and specificity for prediction was achieved by same formula regardless of presentation. Conclusion: In our cohort, overall accuracy was slightly superior among vertex-presenting fetuses without difference in prediction accuracy for small- and large-for-gestational age neonates.

Objective: Our main objective was to study the influence on birth and ultrasound fetal weight of traditional factors in combination with non-traditionally explored predictors such as paternal height to provide a new customized in utero growth model. We also have compared it in our population with other customized and non-customized models. Methods: We collected 5243 cases of singleton pregnancies. An integrated study of the different variables was performed in a multivariate model to predict the fetus birthweight and customized growth curves were created following the Gardosi procedure. Results: Gestational age (P<0.001), parity (P<0.001), maternal age (P<0.001), maternal body mass index (P<0.001), maternal height (P<0.001), parental height (P<0.001), pregnancy-associated plasma protein A (PAPP-A) (P<0.001), free-beta human chorionic gonadotropin (FBHCG) (P<0.013), single umbilical artery (SUA) (P<0.009), region of origin (P<0.001), fetal sex (P<0.001), smoking (P<0.001) and pre-gestational diabetes (P<0.001) showed statistical significance. We created two growth customized models (simple and advance) that have shown good performance in predicting fetal weight at delivery and estimated by ultrasounds. The percentage of small for gestational age (SGA) cases (P10) predicted by the two models at birth were 9.9% and 9%, and for large gestational ages (LGA) (P90) we obtained values of 90.1% and 90.3%. Also, using the fetal weights measured by ultrasounds, we obtained P10 adjusted predictions, 9.2% and 9.4%, for the simpler and advance models, respectively, which were more adjusted than the 0.4, 4.6 and 10.6 obtained using the other compared models. For an easy use of models an app and a nomogram is provided. Conclusion: Using new predictor variables we implemented new growth in utero model, with predictions more adjusted to our population than Spanish customized or Intergrowth 21 st models with better performance for birth and ultrasound fetal weights. We propose using a prediction model that includes parental height.

Objective: To compare first trimester 2D conventional and 3D power Doppler angiography measures in twins and singletons following assisted reproduction. Methods: We prospectively evaluated 50 singleton and 47 twin pregnancies that eventually ended in live births. Patients were recruited from a single assisted reproductive technology (ART) center with standard treatment protocols. Obstetric ultrasound was performed at 8–9 weeks +6 days. Intervillous flow, uteroplacental circulation and uterine artery pulsatility (PI) and resistance index (RI) using two-dimensional (2D) ultrasound examination were evaluated. Using three-dimensional (3D) power Doppler angiography, placental volume and the 3D power Doppler indices from the intervillous and uteroplacental circulation were calculated. Results: Demographic and cycle characteristics were similar in mothers of singletons and twins. Placental volume was significantly (1.6-fold) larger in twins. Vascular density and blood perfusion in the intervillous space were lower in twins. The comparison of the other parameters did not show significant differences between singletons and twins. Conclusion: The data confirm the larger placental volume in twins, denoting a probable higher production of placental hormones that would support an early twin pregnancy. The lower vascular density and blood perfusion in the intervillous space in twins may also confer a reproductive advantage to them.

Background: Recurrent pregnancy loss (RPL) is defined by two or more failed clinical pregnancies. Three to four percent of the couples with RPL have chromosomal aberrations (CA) in at least one partner. The parent’s structural chromosomal abnormalities may cause an unbalanced karyotype in the conceptus which could lead to implantation failure, early or late pregnancy loss, or delivery of a child with severe physical and/or mental disabilities. Objective: To compare live birth rates of couples with CA to couples with normal karyotypes and to investigate medical and obstetric characteristics and pregnancy outcomes of couples with CA and RPL who attend an RPL clinic at a tertiary hospital. Methods: A retrospective cohort study, including 349 patients with two or more consecutive pregnancy losses. The study group consisted of 52 patients with CA, and the control group consisted of 297 couples with normal karyotype. All patients were evaluated and treated in the RPL clinic at Soroka University Medical Center and had at least one subsequent spontaneous pregnancy. Results: The demographic and clinical characteristics were not found to be statistically different between the two groups. The group of carriers of CA had 28/52 (53.8%) live births in their index pregnancy vs. the normal 202/297 (68%) (P=0.067, CI 95%) in the control group. No statistically significant etiology was found between the study group and the control group. A statistically significant difference in live birth rates was found when comparing the total amount of pregnancies [index pregnancy (IP)+post index pregnancy (PIP)] between the study group and the control group (54.16% vs. 67.82%, respectively, P=0.0328). Conclusion: Patients with RPL and CA who have spontaneous pregnancies, have a good prognosis (63.4%) of a successful pregnancy with at least one of the pregnancies (index or post index) resulting in a live birth.

Objective: To identify factors associated with a successful induction of labor in twin pregnancies and associated maternal morbidity. Study design: This was a retrospective review of twin pregnancies ≥24 weeks’ gestation undergoing labor induction from 2011 to 2016. The primary outcome was a successful induction of labor. The secondary outcome was a composite of maternal morbidity, including ≥1 of the following: estimated blood loss (EBL) >1500 ml, blood transfusion, hysterectomy, intensive care unit (ICU) admission or maternal death. Results: Of 104 twin pregnancies undergoing labor induction, 64 (61.5%) had a vaginal delivery of both twins. Multiparity [odds ratio (OR) 12.3, 95% confidence interval (CI) 3.9–38.8, P≤0.005] and maternal age <35 years (OR 2.33, 95% CI 1.1–5.2, P=0.038) were independently associated with vaginal delivery. The overall rate of composite maternal morbidity was 7.7%. Cesarean delivery (CD) was associated with an increased rate of composite maternal morbidity compared to the successful induction group (17.5% vs. 1.6%, P≤0.005). An EBL >1500 ml, uterine atony and the use of ≥1 uterotonic agent were more frequent in the CD group. Conclusions: Multiparous women and those <35 years of age were more likely to have a vaginal delivery. Maternal morbidity is increased in women who required a CD after labor induction compared to those who achieved a vaginal delivery.

The purpose of this study was to investigate when in pregnancy to stop the administration of low dose aspirin (150 mg/daily) so as to prevent fetal growth restriction (FGR) A randomised, placebo-controlled study was designed. The patients were all screened positive using the Fetal Medicine Foundation (FMF) early pregnancy screening test for preeclampsia (PE) and FGR prediction. One hundred and fifty patients were enrolled and divided equally into three groups: A – the controls who received placebo treatment; B – those who received aspirin till 32 weeks of gestation and C – those who received aspirin till 36 weeks of gestation. The mean gestational age at enrollment was similar for all the groups (12.4 weeks). The growth curves, fetal and maternal Doppler measurements and amniotic fluid index (AFI) were monitored every 4 weeks. Also, the outcome of the pregnancy was noted and all the results were compared between the groups. FGR was defined as a fetal weight below the 10 th centile for gestational age. In group C, there were less cases of FGR compared with the other groups: 6% vs. 10% in group B vs. 24% in controls. Also, there was a significant birth weight improvement in this group with a median of 3180 g compared with 2950 g in group B and 2760 g in group A (P=0.01). The gestational age at delivery was similar in all the groups (39 weeks in group C/39.2 weeks in group B/38.6 weeks in group A). In conclusion, low dose aspirin improves the outcome in the selected population and should be offered for prevention of FGR from 12 to 36 weeks.

Objective: It is well known that a short cervix at mid-pregnancy is a risk factor for spontaneous preterm birth in both singleton and twin gestations. Recent evidence also suggests that a long cervix at mid-pregnancy is a predictor of the risk of cesarean section (C/S) in singleton gestation. The purpose of this study was to determine whether a long cervix at mid-pregnancy was associated with an increased risk of C/S in women with twin pregnancies. Methods: We enrolled 746 women pregnant with twins whose cervical length was measured by trans-vaginal ultrasonography at a mean of 22 weeks of gestation and who delivered in our institution. Cases with a short cervix [cervical length (CL) <15 mm] were excluded. Cases were divided into four groups according to the quartile of CL. Results: The rate of C/S increased according to the quartile of CL (47% in the 1 st quartile, 51% in the 2 nd quartile, 56% in the 3 rd quartile and 62% in the 4 th quartile, P<0.005, χ 2 for trend). CL was an independent risk factor for C/S even after adjustment for confounding variables. When confining analysis to women who delivered after a trial of labor (n=418), to nulliparous women (n=633) or to those who delivered at late preterm or full term (n=666), the rate of C/S also increased according to the quartile of CL, and the relationship between CL and the risk of C/S remained significant after adjustment in each group. Conclusion: In women pregnant with twins, long CL at mid-pregnancy was a risk factor for C/S.

Aim: To compare the efficacy of three postoperative feeding regimens on bowel function recovery after term elective cesarean section (CS). Methods: Women recruited for this randomized trial were allocated into three groups. Women in group (A) were instructed to chew sugarless gum for 10 min every 2 h after surgery. Group (B) mothers received IV fluids for 6 h followed by sipping fruit juices sweetened with honey. Group (C) had oral intake of clear fluids after passage of flatus and regular diet with the passage of bowel movement. The main outcome measures were the timing of first return to bowel movement and initiation of regular diet. Results: The mean times to first hearing of bowel sounds, to first flatus passage and to first defecation were significantly lower in group A (10, 17.5 and 28.1 h, respectively) compared to groups B and C [15.1, 24.9 and 36 h (B) and 21.6, 38.8 and 49.4 h (C)]. Initiation of regular diet was significantly earlier in group A compared to groups B and C (21 vs. 27.5 and 40.3 h, respectively). Conclusion: Chewing gum appears to be more advantageous than early or traditional feeding regimens after term elective CS resulting in rapid recovery of bowel function.

Objective: Pregnancies in women affected by a muscular dystrophy are at an increased risk of adverse maternal and neonatal outcomes due to the effect of the disease on the muscular, cardiac and respiratory systems. We sought to evaluate the risk of adverse outcomes within a large population-based cohort study. Methods: We used the data extracted from the Nationwide Inpatient Sample (NIS) to conduct a retrospective population-based cohort study consisting of over 12 million births that occurred in the United States between 1999 and 2013. Births to mothers with muscular dystrophy were identified using the International Classification of Diseases, Ninth Revision (ICD-9) codes and were compared with births to mothers with no maternal muscular dystrophy. Unconditional logistic regression analysis was used to evaluate the adjusted effect of muscular dystrophy on maternal and neonatal outcomes. Results: During the 14-year study period, there was an increasing trend in the incidence of muscular dystrophy, with a cumulative incidence of 7.26 in 100,000 births. Women with muscular dystrophy and their neonates were at a significantly increased risk of adverse pregnancy outcomes: specifically, an increased risk of preeclampsia, preterm premature rupture of membranes, preterm labor, venous thromboembolism, cardiac dysrhythmia, requiring a blood transfusion and giving birth by cesarean section. Neonates born to affected mothers were at a significantly higher risk of being born preterm, with a congenital malformation and suffering intrauterine growth restriction. Conclusion: The risk of several adverse maternal and neonatal outcomes is increased in pregnant women with muscular dystrophy. As such, additional surveillance in order to mitigate the risk of adverse outcomes is warranted in these pregnancies.

Objective: To compare the fetal brain structures assessed in routine sonographic scans during the second and third trimesters in diabetic and normal pregnancies. Methods: In this retrospective study, we measured the head circumference (HC), the transversal diameter of the cerebellum (TCD) and the sizes of the cisterna magna (CM), the cavum septi pellucidi (CSP) and the lateral ventricles (LV) in stored sonographic scans between 20 and 41 weeks of gestation. We compared 231 fetuses of diabetic mothers (diabetic group) to 231 fetuses of normal pregnancies (control group) matched by gestational age. The diabetic group was divided into three subgroups: pre-existing maternal diabetes, diet-controlled gestational diabetes and insulin-dependent gestational diabetes. Results: The mean widths of the CSP and LV were larger in fetuses of diabetic mothers in comparison with the controls (P<0.001, P<0.001; respectively). The sizes of HC, CM and TCD were similar in both groups. These results were consistent across the three subgroups. Conclusions: Diabetes is associated with altered fetal brain development. We would like to introduce the increased widths of CSP and LV as potential markers for gestational diabetes.

Aims: The comparison of body composition parameters between the small for gestational age (SGA) and appropriate for gestational age (AGA) at term, 1, 3 and 5 months corrected ages in very preterm infants. Methods: This cohort study included 92 preterm infants at term age, younger than 32 weeks or <1500 g, classified in two groups: SGA and AGA. Anthropometry and body composition, estimated by air displacement plethysmography, were evaluated at the corrected ages: term and 1, 3, and 5 months. We used the lean mass/fat mass index (LM/FM) at each time point and the weight, length and head circumference SDS gain between the time points. Results: At term age, the SGA preterm infants had less lean mass (g), fat mass (g) and percent fat mass but a greater LM/FM index than AGA infants (P<0.001). At 1 month corrected age the LM/FM index and percent fat mass between the groups became similar. Lower lean mass persisted up to 3 months in the SGA group [4004 g (3256–4595) vs. 4432 g (3190–6246), P<0.001]. During the first month corrected age, the weight SDS gain was higher in SGA preterm infants when compared to AGA preterm infants. However, the SGA preterm infants remained lighter, shorter and with smaller head circumferences than the AGA preterm infants until 3 months of corrected age. Conclusions: The greater lean tissue deficits and an earlier “catch-up” in fat in the SGA group can reflect growth patterns variability since the early life.

General ethical principles such as respect for autonomy and justice could probably be unique around the world but there is an enormous diversity of medical care possibilities that are provided for patients around the globe, and therefore different approaches should be considered depending on the level of health care provided.