Outcome of Multifetal Pregnancy Reduction in Women with a Dichorionic Triamniotic Triplet Pregnancy to a Singleton Pregnancy: A Retrospective Nationwide Cohort Study.

OBJECTIVE: To study the pregnancy outcomes of women with a dichorionic triamniotic triplet pregnancy that was reduced to a singleton pregnancy and to review the literature. METHODS: We performed a nationwide retrospective cohort study. We compared time to delivery and perinatal mortality in dichorionic triplet pregnancies reduced to singletons with ongoing dichorionic triplet pregnancies and primary singleton pregnancies. Additionally, we reviewed the literature on the subject. RESULTS: We studied 46 women with a reduced dichorionic triplet pregnancy and 42 women with an ongoing dichorionic triplet pregnancy. Median gestational age at delivery was 38.7 vs. 32.8 weeks, respectively (p < 0.001). Delivery <24 weeks occurred in 9 (19.6%) women with a reduced triplet pregnancy and 4 (9.5%) with an ongoing triplet pregnancy (p = 0.19). Perinatal survival rates between the reduced group and the ongoing triplet group were not significantly different. CONCLUSION: Multifetal pregnancy reduction in women with a dichorionic triplet pregnancy to a singleton pregnancy prolongs median gestational age at birth. No statistically significant association was found with miscarriage and perinatal survival rates.

Pregnancy outcome after fetal reduction in women with a dichorionic twin pregnancy.

STUDY QUESTION: What are the pregnancy outcomes for women with a twin pregnancy that is reduced to a singleton pregnancy? SUMMARY ANSWER: Fetal reduction of a twin pregnancy significantly improves gestational age at birth and neonatal birthweight, however at an increased risk of pregnancy loss and preterm delivery. WHAT IS KNOWN ALREADY: Women with a multiple pregnancy are at increased risk for preterm delivery. Fetal reduction can be considered in these women. STUDY DESIGN, SIZE, AND DURATION: Retrospective cohort study of 118 women with a twin pregnancy reduced to a singleton pregnancy between 2000 and 2010. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: We compared the outcome of pregnancy in consecutive women with a dichorionic twin pregnancy that was reduced to a singleton pregnancy to that of women with a dichorionic twin pregnancy that was managed expectantly and women with a primary singleton pregnancy. Reductions were performed between 10-23(6/7) weeks' gestation by intracardiac or intrathoracic injection of potassium chloride, mostly for congenital anomalies. We compared median gestational age, pregnancy loss <24 weeks, preterm delivery <32 weeks, neonatal birthweight and perinatal deaths. MAIN RESULTS AND THE ROLE OF CHANCE: We studied 118 women with a twin pregnancy that was reduced to a singleton, 818 women with an ongoing dichorionic twin pregnancy and 611 women with a primary singleton pregnancy. Loss of the entire pregnancy <24 weeks and preterm delivery occurred significantly more in the reduction group compared with the ongoing twin group (11.9 versus 3.1% <24 weeks, P< 0.001 and 18.6 versus 11.5% <32 weeks, respectively, P < 0.001). In the reduction group, the percentage of women without any surviving child was significantly higher compared with the ongoing twin and primary singleton group (14.4, 3.4 and 0.7%, respectively, P < 0.001). Median gestational age was 38.9 weeks (interquartile range (IQR) 34.7-40.3) for reduced pregnancies, 37.1 weeks (IQR 35.3-38.1) for ongoing twin pregnancies and 40.1 (IQR 39.1-40.9) for primary singletons (P < 0.001 for all comparisons). LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were its retrospective character, and the fact that indications for reduction were heterogeneous. WIDER IMPLICATIONS OF THE FINDINGS: In women with a dichorionic twin pregnancy fetal reduction increases median gestational age only at considerable risk of complete early pregnancy loss. STUDY FUNDING/COMPETING INTERESTS: The study was not funded. None of the authors has conflicts of interest.

[Alpha-foetoprotein assessment in amniotic fluid for the detection of neural tube defects: limited added value beyond week 20 ultrasound; retrospective study]. / Alfafoetoproteïnebepaling in vruchtwater voor de detectie van neuralebuisdefecten: beperkte meerwaarde boven de 20-wekenecho; retrospectiefonderzoek.

OBJECTIVE: To evaluate the diagnostic additional value of routine alpha-foetoprotein (AFP) assessment in amniotic fluid for the detection of neural tube defects (NTDs), compared with week 20 ultrasonographic examination. DESIGN: Retrospective. METHOD: We retrospectively determined AFP concentrations in amniotic fluid obtained from 7981 women who had undergone amniocentesis for karyotyping and AFP assessment. An AFP concentration greater than 2.5 times the median was considered abnormal. Women were categorised into 4 groups based on the indication for invasive prenatal diagnostic assessment: advanced maternal age (group I; n = 6179), increased risk of foetal NTDs (group II; n = 258), ultrasonographically confirmed foetal NTDs (group III; n = 55) or other indications (group IV; n = 1489). RESULTS: In group I, 18 of 6179 samples had increased AFP levels (0.3%), 2 of which were associated with NTDs. In group II, 2 of 258 samples had increased AFP levels (0.8%); both were associated with NTDs. Increased AFP levels were found in 44 of 55 samples from group III (80%), and 223 of 1489 samples from group IV (15.0%). CONCLUSION: Routine assessment of AFP in amniotic fluid based on advanced maternal age provides little additional value in the detection of NTDs beyond that of week 20 ultrasound.

Comparing treatment valuations between and within subjects in clinical trials: does it make a difference?

Valuations may be sensitive to biases, especially if elicited alongside randomized clinical trials. We investigated the construction of valuations assigned by women who entered a randomized clinical trial and were allocated to in-hospital or domiciliary monitoring. Women assigned valuations (0-10 visual analogue scale) to the strategy they had been allocated to and to the alternative strategy. Valuations were expressed as a between-subject difference (assigned by the women allocated to the respective strategies) and as within-subject differences (assigned by all women). Domiciliary monitoring was valued higher by the women allocated to that strategy (P = 0.10). In-hospital monitoring was valued higher by the women allocated to that strategy (P = 0.02). The average within-subject differences differed by allocated strategy (P<0.01). The within-subject valuation differences showed large variability between and within groups. An overrepresentation of women favoring domiciliary monitoring and asymmetric treatment experience inflated the average within-subject difference in the domiciliary group but deflated that difference in the in-hospital group. Neither the average between-subject difference nor the average within-subject differences are free of bias. Other study designs probably cannot prevent bias. Comparing within-subject and between-subject differences is instructive.

Risk factors for preeclampsia in nulliparous women in distinct ethnic groups: a prospective cohort study.

OBJECTIVE: To determine whether baseline characteristics during early pregnancy, proposed as potential risk factors for preeclampsia, show differences in prevalence and effects within distinct ethnic groups. METHODS: In a prospective cohort study of 2413 healthy nulliparous women from eight midwives' practices, we analyzed risk factors for preeclampsia (maternal age, body mass index, blood pressure at booking, smoking habit, and abortion history) in white, Mediterranean, Asian, and black women. In a univariate analysis, we estimated the relative risk of preeclampsia for the baseline variables and for ethnicity. In a multivariate analysis, we evaluated the simultaneous effect of the baseline variables in white (n = 1641) and black (n = 317) women. RESULTS: Significant differences were found in the prevalence of the risk factors in different ethnic groups. In the univariate analysis, the relative risk (RR) of preeclampsia in black women was 2.4 (95% confidence interval [CI] 1.1, 5.6) compared with white women. In the multivariate analysis in white women, the adjusted RR of preeclampsia for a diastolic blood pressure at booking above 70 mmHg was 4.4 (CI 0.9, 20.8). Among black women, the adjusted RR of preeclampsia was increased for high maternal age (RR 1.2; CI 1.0, 1.4), but not for a diastolic blood pressure at booking above 70 mmHg (RR 0.8; CI 0.2, 3.9). CONCLUSION: In studies of risk factors for preeclampsia, black women should be analyzed separately from white women.

Cost-minimization analysis of domiciliary antenatal fetal monitoring in high-risk pregnancies.

OBJECTIVE: To compare safety and cost-effectiveness of domiciliary antenatal fetal monitoring (cardiotocography and obstetric surveillance) with in-hospital monitoring in high-risk pregnancies. METHODS: From September 1992 to June 1994, 150 consecutive women with high-risk pregnancies, who would otherwise be monitored in the hospital, entered a randomized controlled trial of in-hospital (n = 74) or domiciliary (n = 76) monitoring. The main outcome measures were neonatal safety (Prechtl neurologic optimality score, the proportion of non-optimals) and cost-effectiveness. To test a two-point difference in mean Prechtl scores (two-tailed o = .05. 1-beta = .80), 150 women were needed. Safety and cost-effectiveness were analyzed according to intention to treat. Conditional on the safety outcomes, a cost-minimization analysis based on actual resource use was performed. Uncertainty of results was explored by sensitivity analyses. RESULTS: Neonatal outcomes were equal. No cost-shifting between the antenatal and postpartum period occurred. Substituting domiciliary for in-hospital monitoring reduced mean (standard deviation) antenatal costs from $3558 ($2841) to $1521 ($1459) per woman (P < .001). If costs were varied by the addition of 50%, costs were still reduced. The magnitude of the reduction was sensitive to the costs of hospital care and less sensitive to the costs of domiciliary monitoring. CONCLUSION: Domiciliary monitoring is safe and reduces costs by one-half. The technique seems transferable to other settings but local circumstances may sometimes hamper its dissemination.

Effect of fetal brainsparing on the early neonatal cerebral circulation.

The effect of antenatal brainsparing on subsequent neonatal cerebral blood flow velocity (CBFV) was studied in very preterm infants. CBFV was determined, using a pulsed Doppler technique, both in the fetal and neonatal period. Neonatally, blood pressure and transcutaneous carbon dioxide tension (TcPCO2) was monitored simultaneously; daily cranial ultrasound examinations were performed. In infants with evidence of brainsparing a higher mean value of CBFV and a different pattern of changes of CBFV during the first week of life was demonstrated compared with infants with normal fetal cerebral haemodynamics. No differences were found in blood pressure and TcPCO2. The incidence of intracranial haemorrhages and of ischaemic echo-dense lesions was also the same for both groups. In a multivariate statistical model gestational age, antepartum brainsparing, and TcPCO2 all contributed significantly in explanation of variation in CBFV. It is speculated that a different setting of cerebral autoregulation related to differences in gestational age or to brainsparing might explain the difference in changes found in neonatal CBFV.

Neurodevelopmental outcome at three years of age after fetal 'brain-sparing'.

Intrauterine growth restriction (IUGR), occurring preterm, may be related to impaired neurodevelopmental outcome. We measured neurodevelopmental outcome (Hempel examination) at the age of three years in a cohort of infants born between 26 and 33 weeks in 1989. Fetuses were studied haemodynamically, using Doppler ultrasound. The ratio between the umbilical and the cerebral artery Pulsatility Index (U/C ratio) was calculated. This is a measure of redistribution of fetal blood preferentially to the brain and this may be a marker of fetal adaptation to placental insufficiency. Impaired fetal growth was also measured by the fetal growth ratio. Neonatal cranial ultrasound was performed to document intracranial haemorrhages and/or ischaemia. From the original cohort of 106 infants, 96 (91%) infants were examined at three years. After adjustment for obstetric variables, adverse Hempel outcome was related to neonatal cranial ultrasound abnormality and low head circumference at three years. Neither the U/C ratio nor fetal growth were independently associated with Hempel outcome. Fetal 'brain-sparing' in IUGR appears to be a benign adaptive mechanism preventing severe brain damage.

A case of pre-eclampsia arising in the fourth pregnancy.

A case of severe pre-eclampsia, with histologically proven eclamptogenic glomerulopathy, appearing in the 32nd wk of the 4th pregnancy is presented. During 'conservative' management with bed-rest and sodium restriction, further deterioration of circulation took place. The results are described of treatment with a combination of a peripheral-acting antihypertensive drug and volume expansion, whereby the fetus could remain in utero until sufficient maturation of the respiratory system could be proven.

Is maternal whole blood viscosity a factor in fetal growth?

Many authors have correlated changes in maternal hemodynamics during pregnancy with fetal growth. Sufficient plasma volume expansion in pregnancy seems mandatory for an optimal reproductive result. A correlation between rheological characteristics (low-shear whole blood viscosity and yield shear stress) and birthweight centiles was found in 26 third-trimester pregnancies. The level of statistical significance (P less than 0.05) was reached in nulliparous pregnancies but not in parous pregnancies. Measurements of whole blood viscosity at low shear rate and yield shear stress seem to provide information on the efficacy of placental perfusion. There have been reports in the literature to support the assumption of the prevalence of low-shear circumstances in the intervillous space. The hypothesis is put forward that, during pregnancy, the changes in maternal hemodynamics influence fetal growth by their impact on the flow through the placenta.

The influence of maternal whole blood viscosity on fetal growth.

To explore the relevance of the rheological properties of maternal blood in pregnancy to fetal growth a study of whole blood viscosity (WBV) was conducted in the early third trimester of 138 pregnancies. A significant negative correlation was found between WBV at low shear rate and birthweight centile. As the rheological parameters were found to be negatively correlated with the placenta coefficient, an independent role for maternal WBV seems likely. When WBV, placental weight and degree of infarction accounted for significant contributions in a logistic regression model, diastolic blood pressure data did not assist in the correct prediction of occurrence of a low birthweight centile (less than 10th). A simplified model is proposed, to explain the mechanisms by which some clinical variables may express their influence on fetal growth. In conclusion, it is suggested that WBV might be considered one of the factors which determine the efficacy of placental perfusion on the maternal side. However, as this variation in efficacy of placental perfusion is only weakly reflected in variations in birthweight, the influence of WBV on fetal growth cannot be very important.

Maternal health, antenatal and at 8 weeks after delivery, in home versus in-hospital fetal monitoring in high-risk pregnancies.

OBJECTIVE: To assess maternal health outcome, comparing high-risk pregnant women to either domiciliary monitoring or in-hospital monitoring, and a low risk pregnant group. DESIGN: Paper and pencil questionnaire, distributed antenatal and 8 weeks after the delivery. SETTING: A university hospital. SUBJECTS: Three groups: 130 high-risk pregnant women, who entered a randomized clinical trial and were allocated to either home (n=69) or in-hospital monitoring (n=61), and a reference cohort of low risk pregnant women (n=55). MAIN OUTCOME MEASURES: Antenatal physical and mental health (RAND36) and social experiences; mode of delivery; complications postpartum; physical health, mental health, and social experiences at 8 weeks postpartum. RESULTS: In all groups, antenatal physical health was considerably lower compared to the physical health of US women aged 18--44 years. Antenatal mental health was lower in high-risk women than in low-risk women (P<0.05). Antenatal maternal health, the mode of delivery, and maternal complications postpartum did not differ significantly between in-hospital and domiciliary monitored women. Eight weeks after delivery, physical health improved considerably in all groups; mental health was significantly lower in high-risks as compared to low-risk women (P<0.01). The allocated monitoring strategy showed a significant effect on mental health at 8 weeks after delivery; the mental health score being lower in the domiciliary monitored group (P<0.05). CONCLUSIONS: At 8 weeks after the delivery, physical health improves substantially in all groups. Mental health is higher in low-risks than in high-risks. Within the high-risk group domiciliary and in-hospital monitored women have the same physical maternal outcome at 8 weeks after delivery. However, mental maternal health in in-hospital monitored women at 8 weeks was probably biased by a medicalization effect.

High risk pregnancy monitored antenatally at home.

OBJECTIVE: Is domiciliary antenatal fetal surveillance for selected high risk pregnancies, a feasible alternative for hospital admission? DESIGN: A randomized controlled trial conducted at the Academical Medical Centre, Amsterdam, The Netherlands. SUBJECTS: Between September 1992 and June 1994, 76 women were at random allocated to domiciliary care and 74 women to hospital care. Criteria for inclusion were hypertension (26%), fetal growth retardation (24%), post term pregnancy (23%), diabetes (24%), preterm rupture of membranes (2%) and previous recurrent antenatal death (1%). MAIN OUTCOME MEASURES: Primary outcome measure was perinatal morbidity, measured by Prechtl's neonatal neurological optimality score. Secondary outcome variables were the occurrence of complications, obstetric interventions at labour, birthweight, gestational age at delivery and maternal and neonatal admission rates. RESULTS: In both groups there was one case of perinatal mortality. In both treatment groups the median of the neurological optimality score was found at 59. Also secondary outcome variables did not show significant differences. CONCLUSION: Domiciliary antenatal care for selected women with high risk pregnancy is feasible considering obstetric outcome.

Interobserver variability of the neurological optimality score.

OBJECTIVE: To assess the interobserver reliability of the neurological optimality score. STUDY DESIGN: The neurological optimality score of 21 full term healthy, neurologically normal newborn infants was determined by two well trained observers. RESULTS: The interclass correlation coefficient was 0.31. Kappa for optimality (score of 58 or higher) was 0.19. A systematic difference of 1.3 points between the two observers was present. CONCLUSIONS: The interobserver variability of the neurological optimality score of the newborn infant is substantial. The subtle judgement of elicited responses as optimal or non-optimal proved to be especially critical in this concordance study. A difference of at least two points in the score is considered as a valid endpoint for comparative studies. If two or more observers are involved in the neurological examination of the newborn infant in a study to assess influences on perinatal morbidity, frequent re-instruction sessions are recommended.

Intensification of fetal and maternal surveillance in pregnant women with hypertensive disorders.

OBJECTIVE: To examine the need to intensify fetal and maternal surveillance in pregnant women with mild pregnancy hypertension. METHODS: The multi-center cohort study in 2413 healthy nulliparae analyzed differences in hypertension-related adverse events (small-for-gestational age, perinatal mortality, eclampsia, abruptio placentae and HELLP syndrome) according to maximum diastolic blood pressure and proteinuria. RESULTS: Compared to the reference group (diastolic blood pressure 70-85 mmHg) (n = 1882) the relative risks of adverse fetal and maternal outcome in 34 proteinuric hypertensive women were 8.9 (95% CI 3.3-24.1) and 41.5 (95% CI 9.7-178.4), respectively. In 203 non-proteinuric women with a maximum diastolic blood pressure of > or = 95 mmHg only the relative risk of adverse maternal outcome was increased (11.6, 95% CI 3.1-42.8), but it was not increased in 230 non-proteinuric women with a maximum diastolic of 90 mmHg. CONCLUSIONS: Intensified surveillance in women with mild pregnancy hypertension is not indicated and should be reserved for groups with increased fetal and maternal risk.

[Poor prognosis in children with ultrasonographically diagnosed abnormalities of the central nervous system]. / Sombere prognose bij kinderen met prenataal echoscopisch vastgestelde afwijkingen van het centrale zenuwstelsel.

OBJECTIVE: Long-term follow-up of children with a prenatally diagnosed malformation of the central nervous system. DESIGN: Descriptive study. SETTING: Department of prenatal diagnosis, Academic Medical Center, Amsterdam, the Netherlands. METHODS: Evaluation of all documented ultrasound examinations between 1985 and 1990 (6 years). These ultrasound examinations were performed in women with an increased risk for a foetal malformation, because of obstetrical complications or when a foetal malformation was suspected on ultrasound examination performed elsewhere. Paediatricians and general practitioners were asked to provide follow-up data on the children who were still alive. RESULTS: Seven out of 67 foetuses with a prenatally diagnosed malformation of the central nervous system lived longer than one month. Two out of these 7 children developed normally, one child died after several years and four children were severely retarded. The two children who developed normally both had mild hydrocephaly. CONCLUSION: Prognosis of children with a prenatally diagnosed malformation of the central nervous system is poor. Children with mild hydrocephaly may have a better prognosis.

[3 examples of fetal genetic neuromuscular disorders which lead to hydramnion]. / Drie voorbeelden van genetische neuromusculaire aandoeningen bij de foetus die leiden tot hydramnion.

Causes of polyhydramnios include foetal neuromuscular disorders which cause inability of the foetus to swallow amniotic fluid. Three examples of such disorders are presented: X-linked myotubular myopathy, congenital myotonic dystrophy, and congenital nemaline myopathy. It is concluded that in case of polyhydramnios a search for foetal neuromuscular disease should be carried out. This implies ultrasound evaluation of the foetal movements, especially swallowing movements, neurological examination of the mother for myotonic dystrophy and examination of the newborn, which in selected cases includes muscle biopsy. Foetal neuromuscular disorders are usually genetic in origin. This adds to the need for accurate diagnosis and proper genetic counseling.

[Third circulation: twin transfusion syndrome]. / Derde circulatie: tweelingtransfusiesyndroom.

The estimated incidence in the Netherlands of serious previable twin-to-twin transfusion syndrome is 50-100 cases per year. The polyhydramnion-oligohydramnion sequence is the most prominent feature. Prognosis without treatment is dismal: previable preterm birth. Risk of serious morbidity in the surviving twin in case of foetal demise of the other is impressive. Once the diagnosis of monochorionicity has been made in the first trimester, detailed ultrasound examination is mandatory for early recognition of the development of the syndrome, as therapeutic options exist. Therapeutic options include piercing of the intertwin membrane, repeated amniocenteses or laser occlusion of the chorionic vasculature. In seven Dutch centres over three years time 61 cases were identified: 36 needed intervention; 63 (of the 122) children survived, 10 with longterm morbidity.

Maternal whole blood viscosity in pregnancy hypertension.

Hemoconcentration is prominent in preeclampsia. Concomitant changes in the flow properties of maternal blood, i.e. in whole blood viscosity (WBV), might be related to the occurrence of fetal or maternal complications. To test this hypothesis, WBV was estimated in 228 pregnancies. Patients were assigned to one of four groups according to maximum diastolic blood pressure. Significantly higher WBV values were found in the more hypertensive groups throughout pregnancy. WBV data, obtained between 26 and 36 weeks of amenorrhea, contributed significantly, independently of hypertension, to the prediction of fetal outcome. With regard to maternal complications, no significant contribution of WBV data could be established independently of blood pressure. The results support the hypothesis that WBV is a determining factor in the efficacy of placental perfusion.