Can anomalies of fetal brain circulation be useful in the management of growth restricted fetuses?

Assessment of the fetal cerebral circulation provides important information on the hemodynamic changes associated with chronic hypoxia and intrauterine growth restriction. Despite the incorporation of new US parameters, the landmark for the fetal brain hemodynamic evaluation is still the middle cerebral artery. However, new vascular territories, such as the anterior and posterior cerebral arteries, might provide additional information on the onset of the brain sparing effect. The fractional moving blood volume estimation and three-dimensional power Doppler ultrasound indices are new techniques that seem to be promising in identifying cases at earlier stages of vascular deterioration; still, they are not available for clinical application and more information is needed on the reproducibility and advantages of three-dimensional power Doppler ultrasound blood flow indices. In the past, the brain sparing effect was considered as a protective mechanism; however, recent information challenges this concept. There is growing evidence of an association between brain sparing effect and increased risk of abnormal neurodevelopment after birth. Even in mild late-onset intrauterine growth restriction affected fetuses with normal umbilical artery blood flow, increased cerebral blood perfusion can be associated with a substantial risk of abnormal neuroadaptation and neurodevelopment during childhood.     

Do intrauterine growth restricted fetuses of the hypertensive and normotensive mothers differ from each other?

Purpose

To investigate if normotensive and hypertensive patients with intrauterine growth restricted (IUGR) fetuses were different with respect to maternal and fetal characteristics and Doppler flow.

Methods

The records of patients with IUGR fetuses who had to be delivered before 34th gestational week because of fetal distress were examined. Early Doppler abnormalities were defined as increased umbilical artery resistance and redistribution of blood flow in the middle cerebral artery while late Doppler abnormalities were defined as the absence or reversal of umbilical artery blood flow and Doppler flow changes in venous Doppler. t Test, Chi-square test and Mann–Whitney U test were used for the comparison of data as appropriate. p?<?0.05 was considered statistically significant.

Results

Thirty-six patients were hypertensive while 42 were normotensive. Gestational week at admission for hypertensive and normotensive groups (30.8?±?3.6 vs. 32.3?±?3.1) (p?=?0.057), time to delivery (7.1?±?12.6 vs. 4.3?±?9.1?days) (p?=?0.267) and gestational week at delivery (31.8?±?3.1 vs. 32.9?±?2.9) (p?=?0.117) were similar. Birth weight was significantly lower (1242?±?534 vs. 1516?±?504?g) (p?=?0.02) in the normotensive group. The frequency of having oligohydramnios (64.2?% for normotensive and 44.4?% for hypertensive patients) (p?=?0.079) was similar in both groups. Early Doppler abnormalities were more common in hypertensive group (75 vs. 40.5?%) (p?=?0.001) while late Doppler abnormalities were more common in normotensive group (25 vs. 59.5?%) (p?=?0.001).

Conclusion

Birth weight was lower and late Doppler abnormalities were more common in the normotensive group while early Doppler abnormalities were more common in hypertensive group.     

Are antenatal steroids beneficial to severely growth restricted fetuses?

Abstract

Antenatal steroids (AS) have been shown to enhance fetal maturation in preterms and to improve outcome. The aim of this study was to evaluate the efficacy of AS in premature severely intrauterine growth restricted infants. The electronic data of 149 inborn, single infants born 24 to 31 6/7 weeks of GA and with a BW?≤?3rd percentile were reviewed. Infants with congenital anomalies and syndromes were excluded. We compared the outcome of those who received 2 doses of AS (group A, 87 infants) with those who did not receive AS (group B, 62 infants). Sixty-eight infants in group A and 53 in group B were discharged home alive. AS did not improve the neonatal outcome, with the exception of a better cord pH and 5-min Apgar and we did not observe a significant difference in the Griffith’s test at 2 years of corrected age, although there was a trend to a higher incidence of severe global delay in the steroid group. In view of the potential cerebral and CVS risks associated with high circulating steroids, the indications for AS in such a population need to be re-evaluated.     

The clinical value of maternal and fetal Doppler parameters in low-risk postdates pregnancies – a prospective study

Objective: The objective of this study is to determine the clinical significance of maternal and fetal ultrasound Doppler flow indices in postdates pregnancies.

Methods: This prospective study comprised 120 low-risk pregnant women beyond 40 weeks of gestation. All participants underwent Doppler assessment including of fetal middle cerebral artery (MCA), umbilical, and uterine arteries. Perinatal outcomes were recorded and evaluated for possible associations with Doppler flow values. Adverse perinatal outcomes were defined as umbilical cord arterial pH <7.1, Apgar score <7 at 5?min, neonatal admission to a neonatal intensive care unit, and emergency cesarean section due to abnormal intrapartum cardiotocogram

Results: Adverse perinatal outcome rate was 17.5% (n?=?21). Doppler indices of umbilical artery, MCA, uterine artery and the cerebroplacental ratio (CPR) did not differ significantly between pregnant women with and without adverse perinatal outcomes. Neonatal birth weight was found to correlate negatively with umbilical artery Doppler indices, including the peak systolic to end diastolic ratio (p?=?.04), the resistance index (p?=?.02), and the pulsatility index (p?=?.01). Doppler values of the uterine artery, MCA and CPR did not correlate with neonatal birth weight.

Conclusions: The contribution of maternal and fetal ultrasound Doppler to the prediction of adverse perinatal outcomes in low-risk postdates pregnancies is low. Hence, performing routine Doppler examination as part of postdates pregnancy assessments is unlikely to yield significant clinical benefit.     

Optimising enteral nutrition in growth restricted extremely preterm neonates – a difficult proposition

Background: Optimising enteral nutrition of extremely preterm neonates (EP: Gestation <28 weeks) with intrauterine growth restriction (IUGR) has always been difficult considering their higher risk of necrotising enterocolitis (NEC), and frequency of feed intolerance.

Aim: To evaluate the nutritional outcomes in EP neonates with IUGR.

Methods: Data on demographic characteristics, feeding details (e.g. type of milk, postnatal age at start), and outcomes to discharge or death were collected from the medical notes for all EP neonates, who survived first 72?h of life, between January 2009 and December 2010. A standardised feeding protocol was followed during the study period.

Results: 38/220 (17.3%) EP neonates admitted during the study period had IUGR. The mean (IQR) age at start of minimal enteral nutrition [7 (5–10) versus 5 (4–8) days, p?=?0.005), and nutritional (1?ml/2hourly) feeds [12 (8–15) versus 9 (7–13) days, p?=?0.034] was significantly delayed in IUGR compared to non-IUGR neonates. IUGR neonates reached full enteral feeds (150?ml/kg/day) at a significantly late median (IQR) postnatal age [32 (21–40) versus 24 (17–31) days, p?=?0.009), taking longer time to achieve this milestone [20 (15–34) versus 16 (12–4) days, p?=?0.008). The incidence of postnatal growth restriction was significantly higher in IUGR versus non-IUGR (73% versus 45%, p?=?0.003) neonates. The incidence of?≥?Stage II NEC was low [18/220 (8.1%)] to make valid statistical comparisons.

Conclusion: Optimising enteral nutrition in growth restricted extremely preterm neonates is difficult using the current strategies for enteral nutrition.     

IMA and IMAR in serum and saliva of preeclampsia – a preliminary study

Introduction: Oxidative stress could play a role in the development of preeclampsia. Ischemia modified albumin (IMA) is a oxidatively modified form of albumin. Objective: To evaluate the levels of salivary and serum IMA and IMA: albumin ratio (IMAR) in preeclampsia and with its severity and investigate their correlation with the fetal birth weight. Methods: This case control study was conducted on 50 preeclamptic (32 mild and 18 severe cases) and 50 normal pregnant controls. Blood and saliva were obtained to measure albumin, IMA and IMAR was calculated. Results: serum and salivary IMA and IMAR were significantly increased in preeclampsia. Although the increase in serum was in accordance with the severity, it was not so in the saliva. Yet, salivary IMAR showed significant difference between controls and mild preeclampsia. There was a negative correlation between IMA and albumin in both serum and saliva. A weak negative correlation was seen between the serum IMAR and fetal birth weight (r?=??0.293; p?Conclusion: This study is an evidence for involvement of oxidative stress in the pathogenesis of preeclampsia, which is reflected in serum and saliva. Salivary IMAR could be a better marker for early prediction of preeclampsia.     

Serum placental growth factor and fms-like tyrosine kinase 1 during first trimester in Chinese women with pre-eclampsia – a case–control study

Objective.?To investigate the association between first trimester maternal placental growth factor (PlGF) and fms-like tyrosine kinase 1 (sFlt-1) levels with subsequent development of pre-eclampsia (PE).

Methods.?This is a matched case–control study using stored serum samples collected from non-smoking Chinese women with singleton pregnancies who underwent first trimester screening for aneuploidy. Each case that developed PE was matched with a control whose maternal age, weight, gestational age and date of blood collection were within ±2 years, ±5?kg, ±1 day, and?±2 weeks of the index case, respectively. Non-parametric paired test was used to compare the PlGF and sFlt-1 levels. PlGF and sFlt-1 were transformed to their equivalent multiple of the median (MoM) using the matched control as the expected median value. The 95% confidence interval (CI) of the estimated median PlGF and sFlt-1 MoM in those with PE was determined.

Results.?The median PlGF level in the 27 study cases with PE was lower than that of the matched controls (42.9?pg/ml versus 59.8?pg/ml; p?=?0.001). The median PIGF MoM was 0.71 (95% CI 0.63–0.92). There was no statistically significant difference in sFlt-1 levels between those with PE and their matched control (p?=?0.648). The median sFlt-1 MoM was 1.01 (95% CI 0.65–1.3).

Conclusions.?Women who developed PE had lower serum PlGF levels but normal sFlt-1 levels in the first trimester.     

Assessment of nitrite oxide and maternal–fetal Doppler parameters during pregnancy

Objective: The objective was to evaluate and compare the whole blood nitrite concentration in the three trimesters of pregnancy. Additionally, we investigate whether there is any relation between nitrite concentrations and Doppler ultrasound analysis of some maternal and fetal vessels.

Methods: Thirty-three healthy pregnant women were examined at the first (11–14 weeks), second (20–24 weeks) and third trimester (34–36 weeks) of pregnancy. In the three exams, we determined the maternal whole blood nitrite concentration and uterine arteries Doppler analysis to determine pulsatility index (PI), and resistance index (RI). In the second and third trimester we also performed fetal umbilical and middle cerebral arteries PI and RI. We compared the concentrations of nitrite in three trimesters and correlated with Doppler parameters.

Results: No difference was observed in the whole blood nitrite concentrations across trimesters: 151.70?±?77.90?nmol/ml, 142.10?±?73.50?nmol/ml and 147.10?±?87.30?nmol/ml; first, second and third trimesters, respectively. We found no difference in correlation between whole blood nitrite concentration and Doppler parameters from the evaluated vessels.

Conclusions: In healthy pregnant women, the nitrite concentrations did not change across gestational trimesters and there was also no strong correlation with Doppler impedance indices from maternal uterine arteries and fetal umbilical and middle cerebral arteries.     

Maternal factors in the origin of isolated anorectal malformations – a population-based case–control study

Objective: In most patients affected by isolated anorectal malformation (IARM), the etiology is unknown. Thus, the aim of this study was to analyze the possible role of maternal risk factors in the origin of IARM.

Methods: The study samples included 231 cases with IARM, 361 matched and 38 151 population controls without any defect in the population-based large dataset of the Hungarian Case–Control Surveillance of Congenital Abnormalities, 1980–1996. Cases with IARM were evaluated in the function of maternal diseases and related drug use.

Results: The findings of this case–control study suggested that cases with IARM have an obvious male excess. The mothers of cases with IARM had a lower incidence of severe nausea and vomiting in pregnancy and a higher incidence of acute infectious diseases in the urinary tract.

Conclusions: Lack of nausea and vomiting in pregnancy and the higher incidence of urinary tract infections may have a role in the development of IARM.     

Oxidative stress in preeclamptic mother – newborn dyads and its correlation with early neonatal outcome – a case control study

Background: Preeclamptic mothers are likely to have increased oxidative stress during pregnancy which can adversely affect the outcome in their neonates.

Objectives: To measure the oxidative stress in preeclamptic mother- newborn dyads and correlate it with the immediate neonatal outcome.

Methods: This case control study conducted in a tertiary care teaching hospital, South India included 71 preeclamptic mothers – newborn dyads (cases) and 72 normal mothers – newborn dyads (controls). Biochemical parameters including total antioxidant status (TAS), protein carbonyls and malondialdehyde levels (MDA) were measured in both maternal and cord blood. Association between these oxidative stress parameters and early neonatal outcome was studied.

Results: All oxidative stress markers were higher in the preeclampsia group compared to the controls. Cord blood protein carbonyl levels had significant correlation with maternal levels. Prematurity, low-birth weight, respiratory distress syndrome (RDS), early onset sepsis (EOS) and intra-uterine growth restriction (IUGR) were more among cases. Early neonatal outcomes like death, IUGR, EOS, and RDS had significant correlation with protein carbonyl levels among the cases.

Conclusions: Oxidative stress is increased in preeclamptic mother – newborn dyads. Increased protein carbonyl levels in preeclampsia correlate with adverse early neonatal outcome.     

Late preterm and early term: when to induce a growth restricted fetus? A population-based study

Purpose: (1) Compare fetal and neonatal morbidity and mortality associated with induction of labor (IOL) versus expectant management (EM) in women with isolated fetal growth restriction (FGR) between 34^0/7 and 38^6/7 weeks; (2) Determine optimal gestational age for delivery of such fetuses.

Materials and methods: A retrospective population based cohort study of 2232 parturients with isolated FGR, including two groups: (1) IOL (n?=?1428); 2) EM (n?=?804).

Results: IOL group had a lower stillbirth and neonatal death rates (p?=?.042, p?p?=?.001, p?=?.039). In the early term cohort, EM was associated with a higher rate of NRFHR and low 1?min Apgar scores (p?=?.003, p?=?.002). IOL at 37 weeks protected from stillbirth but not from adverse composite neonatal outcomes.

Conclusions: IOL of FGR fetuses at 37?weeks had a protective effect against stillbirth. In addition, at late preterm, it is associated with lower rates of stillbirth, neonatal death, and NRFHR.     

Assessment of fetal growth in twins: Which method to use?

Fetal growth restriction contributes to the excess perinatal mortality and morbidity associated with twin pregnancies. Regular ultrasound monitoring for fetal growth restriction is an essential component of antenatal care of twin gestations. It is accepted that twins have divergent growth trajectories around 28–30 weeks’ gestation and are born smaller compared to singletons. Despite this well-established difference in fetal growth, twin pregnancies have been traditionally managed using growth standards developed for singleton pregnancies. Numerous recent studies have demonstrated a strong case supporting the use of twin-specific growth standards, but clinical implementation has been lacking. In this paper, we will review the evidence on factors affecting fetal growth, the rationale for twin-specific reference charts, clinical evidence for their use, and future direction of research. Applying singleton growth standards to twin pregnancies inflates the abnormal growth rate, and recent clinical evidence from several studies suggests that they are too stringent for classification of twins. The association of adverse perinatal and maternal outcomes such as perinatal death, preterm birth, neonatal care unit admission, hypertensive disorders of pregnancy, and composite neonatal morbidity is stronger when classification is made using twin-specific standards compared to singletons.     

Predicting outcome in 259 fetuses with agenesis of ductus venosus – a multicenter experience and systematic review of the literature*

Objective: To evaluate prenatal predictors of postnatal survival in fetuses with agenesis of ductus venosus (ADV).

Methods: This retrospective study reviewed our experience and the literature between 1991 and 2015. Prenatal findings were evaluated and perinatal morbidity and mortality was documented.

Results: A total of 259 cases were included in the present analysis from our centers and 49 published studies (15 patients from our retrospective cohort review and 244 from literature review). The intrahepatic and extrahepatic shunts were present in 32.0% (73/226) and 67.7% (153/226), respectively. Cardiomegaly (n?=?64/259, 24.7%), hydrops (n?=?31/259, 12.0%) and amniotic fluid abnormalities (n?=?22/259, 8.5%) were among the most frequent initial ultrasound findings. One hundred and forty-seven fetuses (56.8%) had ADV without structural anomalies while 112 (43.2%) had associated anomalies (cardiac anomalies (n?=?66), extra-cardiac anomalies (n?=?19) and both cardiac and extra-cardiac anomalies (n?=?27)). The mean gestational age (GA) at ultrasound diagnosis was 22.9?±?6.9 weeks while the mean GA at delivery was 34?±?7.5 weeks. The overall neonatal survival was 57.1% (n?=?148/259). The following factors were associated with survival: advanced maternal age, earlier GA at diagnosis, prematurity, increased nuchal translucency, pericardial effusion, associated cardiac defects (especially AVSD), chromosomal abnormalities, hydrops, hygroma and limb anomalies.

Conclusion: Fetal hydrops, the presence of associated congenital anomalies and premature delivery are associated with poor prognosis in fetuses with ADV.     

Impact of maternal fasting on fetal well-being parameters and fetal–neonatal outcome: a case–control study

Objective: To assess the impact of maternal fasting on fetal well-being parameters and neonatal outcome.

Methods: Two-hundred ten healthy women with singleton uncomplicated pregnancies at 36–40 weeks’ gestation who had fasted for 12–16 h were defined as the study group with 240 healthy non-fasted pregnant women matched for age, parity and gestational age were defined as the control group. Both groups were subjected to tests of fetal well-being in the form of non-stress test (NST), modified biophysical profile and Doppler indices of the umbilical and middle cerebral arteries (MCA). Women were followed-up till delivery to record the obstetric outcome.

Results: There was no significant difference between the two groups regarding the reactivity of NST, modified biophysical scores, Doppler indices of the umbilical and MCA (resistive index, pulsatility index and systolic/diastolic ratio) and the cerebroplacental ratio (p?>?0.05). There was no significant difference between the two groups regarding the gestational age at delivery, mode of delivery, neonatal weight, 5-min Apgar scores and admission to neonatal intensive care unit (p?>?0.05).

Conclusions: Short-term maternal fasting has no deleterious effect on fetal well-being parameters or neonatal outcome. Pregnant women who desire fasting, should be reassured regarding the health of their babies.     

Illegal births and legal abortions – the case of China

Background  

China has a national policy regulating the number of children that a woman is allowed to have. The central concept at the individual level application is "illegal pregnancy". The purpose of this article is to describe and problematicize the concept of illegal pregnancy and its use in practice.     

Illegal births and legal abortions – the case of China

Background  

To investigate whether low birth weight increases the risk of myocardial infarction later in life in women.     

Possible association between hyperthyroidism in pregnant women and obstructive congenital abnormalities of urinary tract in their offspring – a population-based case–control study

Objective.?The teratogenic potential of some antithyroid drugs is known, but the aim of the study was to estimate the risk of congenital abnormalities (CAs) in the offspring of pregnant women with hyperthyroidism with or without antithyroid drug treatment.

Method.?Comparison of the occurrence of medically recorded hyperthyroidism who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case–Control Surveillance System of CAs, 1980–1996. Of 22,843 cases with congenital abnormalities, 71 (0.31%) while of 38,151 controls, 116 (0.30%) had mothers with hyperthyroidism. The rate of hyperthyroidism in the mothers of cases with different CAs and in the mothers of matched controls was compared.

Results.?Preeclampsia–eclampsia occurred more frequently in pregnant women with hyperthyroidism without antithyroid treatment. The analysis of specific groups of CAs showed an association between hyperthyroidism in pregnant women and obstructive defects of urinary tract in their children.

Conclusions.?The lack of appropriate treatment of pregnant women affected with hyperthyroidism seems to be the major problem, because it would be necessary to prevent the hyperthyroidism related risks of pregnancy complications and CAs which exceed the risk of antithyroid medication in these pregnant women.     

Assessment of sonographer nuchal translucency measurement performance – central tendency and dispersion

Objective.?To assess center and sonographer nuchal translucency (NT) measurements that were performed as part of routine prenatal screening for Down syndrome.

Methods.?Sonographers were assessed for measures of central tendency and dispersion by comparing them with expected population median and dispersion parameters. NT measurements were converted to multiples of the expected NT values according to CRL (NTMoM) and transformed to their log₁₀ equivalent (log₁₀ NTMoM). Central tendency and measurement were assessed by checking whether the median of the NTMoM distribution and SD of the log₁₀ NTMoM distributions were, respectively, within 5% or 10% of the expected median of 1 and SD of 0.1. Assessment was performed using both the Center specific and Fetal Medicine Foundation (FMF) reference NT for Crown rump length (CRL).

Results.?The median NT MoM was 0.95 MoM using the FMF reference and 1.01 MoM when assessed using our center specific reference median. The difference between the center and FMF derived NT MoMs was statistically significantly (p?<?0.0001). NTMoM medians increased over time at a rate of 0.0099 MoM per year while log₁₀ NT MoM measurement dispersement was similar to the 0.1 value expected and decreased by 0.0048 per year.

Conclusion.?Centers should routinely monitor the quality of NT measurements used to estimate Down syndrome screening risk and should provide individualized feedback to sonographers of their measures of central tendency and dispersion to ensure consistent and improved performance. NT reference medians adopted from other populations should be assessed and validated against a centers own measurement distribution.