Treatment of fetal anemia in Rh isoimmunized pregnancies with intrauterine fetal blood transfusion

Introduction

Despite the availability of prophylactic rhesus immune globulin, hemolytic disease of the newborn and fetal death (hydrops fetalis) due to rhesus alloimmunization, is still a major contributor to perinatal morbidity and mortality in India. Pregnancy outcome after fetal therapy with ultrasound guided intrauterine transfusion (IUT) for fetal anemia was studied.

Methods

A prospective cohort study of 99 Rh isoimmunized pregnancies, Indirect Coomb’s test Positive (ICT > 1:16) was conducted from July 2002 to June 2007. Intensive fetal monitoring by sériai ultrasound and middle cerebral artery peak systolic velocity using Color Doppler was performed to detect fetal anemia. When necessary, invasive testing with cordocentesis for Hb, PCV was per-formed if pregnancy was less than 32–34 weeks gestation. If PCV was <30, or there was fetal hydrops, Ultrasound guided intrauterine transfusion was carried out by the intravascular (IVT) or the intraperitoneal (IPT) routes. Primary outcome variables were fetal survival in relation to gestational age and procedure related factors.

Result

Of 99 pregnancies, 43 cases (25 — hydropic, 18-nonhydropic fetuses) required 135 intrauterine blood transfusions. The rest 56 pregnancies were managed conservatively and did not need IUT. IUTs were performed when indicated starting from 16 weeks (IPT) and 21 weeks (IVT) of gestation by the intraperitoneal / intravascular routes respectively. Pre-transfusion Hb ranged from 3g% to 8g%. The amount of blood transfused varied from 10 ml to > 110 ml depending on the period of gestation and degree of fetal anemia. The number of transfusions per pregnancy was 1–7, at intervals of 1–4 weeks, till delivery at 28 to 36 weeks of gestation. Survival of hydropic babies (88%) was almost similar to those without hydrops (83.3%) Prognosis was slightly better in Rh isoimmunized pregnancies not requiring IUT (94%) compared to fetuses receiving transfusions (85.6%)

Conclusion

Intrauterine fetal blood transfusion was found to be the only life saving therapy, and very effective in the management of preterm Rh isoimmunized pregnancies. Results are comparable with the best centers in the world, hence early referral to specialized centers with expertise of specialized intensive fetal monitoring for early diagnosis of fetal anemia, and of intrauterine fetal blood transfusion are important for optimal perinatal outcome.     

Effect of human embryonic morphological development on fetal growth parameters: the Rotterdam Periconceptional Cohort (Predict Study)

Research question

Is embryonic morphological development according to the Carnegie stages associated with pregnancy outcome?

Sonographic evaluation of kidney parenchymal growth in the fetus

Objective

The aim of the study was to establish a nomogram for renal parenchymal thickness throughout pregnancy.

Methods

One-hundred and twenty-eight healthy women with singleton, well-dated, uncomplicated second- or third-trimester pregnancies were prospectively evaluated for renal parenchymal thickness on routine ultrasound scans. The renal parenchyma was measured in transverse and sagittal sections using predefined criteria.

Results

There were no differences in anterior or posterior parenchymal measurements in either plane by fetal sex. On sagittal-section analysis, no differences were noted between the right and left kidneys. A nomogram was established on the basis of the findings. The results showed constant linear growth of the fetal parenchyma during pregnancy.

Conclusions

The normal fetal parenchyma grows at a constant, linear rate throughout pregnancy. The nomogram formulated may serve as a basis of future studies of the correlation of parenchymal thickness with postnatal kidney function in fetuses with urinary tract anomalies.     

The impact of different sides of the absent umbilical artery on fetal growth in an isolated single umbilical artery

Purpose

The aim of this study was to determine whether laterality of an absent umbilical artery (AUA) is associated with fetal growth in fetuses with isolated single umbilical artery (SUA).

Methods

Fifty singleton pregnancies were studied, including 26 cases with a right AUA and 24 cases with a left AUA in isolated SUA, and 200 singleton pregnancies with a three-vessel cord. Delivery data, including gestational age and birth weight and height, were recorded. Compare the birth weight and height in fetuses between the different sides of an AUA and the three-vessel cord by covariance analysis.

Results

The mean difference was 0.25 kg (SD 0.05; P < 0.05) in birth weight between fetuses with a left AUA and a three-vessel cord. The mean difference was 1.03 cm (SD 0.56; P < 0.05) in birth height between fetuses with a left AUA and a three-vessel cord. No significant differences were observed in birth weight and height between fetuses with a right AUA and those with a three-vessel cord.

Conclusion

Our data suggest that the birth weight and height of fetuses with a left AUA in isolated SUA are lower than those with a three-vessel cord.     

Human chorionic gonadotropin as a measure of pregnancy duration

Objective

To compare gestational age (GA) estimates in early pregnancy, determined by last menstrual period (LMP), human chorionic gonadotropin (hCG) concentration, ultrasound crown–rump length (Hadlock formula), and ovulation day (luteinizing hormone surge plus 1 day).

Methods

Female volunteers seeking to conceive (at 5 US sites) collected daily early-morning urine for up to 3 menstrual cycles. Pregnant women underwent ultrasound dating scans. Conception cycle urine was quantitatively assessed for luteinizing hormone and hCG. Summary statistics for GA using each reference method were determined (n = 131).

Results

Correlation between GA determined by ultrasound and ovulation day was excellent (maximum difference 10 days); however, pregnancies dated by ultrasound were 3 days advanced. The difference between LMP estimates and estimates based on ovulation day or ultrasound was 9 and 12 days, respectively. A uniform rise in hCG on each day of pregnancy was seen using all reference methods. The accuracy of hCG measurement in determining the week since conception was more than 93%.

Conclusion

Methods for establishing pregnancy duration vary in their accuracy and their GA estimates. The rise in hCG concentration in early pregnancy is uniform and therefore hCG levels provide the most accurate, early estimation of GA in single, viable pregnancies.ClinicalTrials.gov:NCT01077583     

Male gender predisposes to prolongation of pregnancy

OBJECTIVE: The purpose of this study was to evaluate the association between fetal gender and prolonged pregnancy. STUDY DESIGN: All deliveries in Sweden between 1987 and 1996 were evaluated for participation in this study. Inclusion criteria included (1) singleton pregnancy, (2) the absence of apparent congenital or chromosomal anomalies, (3) accurate dating established by early second trimester ultrasound examination, and (4) gestational age at delivery of > or =37 weeks (ie, > or =259 days). Initially, we calculated the mean gestational age at delivery and the percentage of prolonged pregnancies by fetal gender. Subsequently, the Mantel-Haenszel chi-square analysis was used to calculate the weekly odds ratios and their corresponding 95% confidence intervals for the delivery of a male fetus beyond 37 weeks of gestation. RESULTS: The study population comprised 656,423 deliveries; 333,192 were male deliveries, and 323,231 were female deliveries (male/female ratio, 1.03). The mean gestational age at delivery was significantly higher in male fetuses (280.6 +/- 8.9 days vs 279.8 +/- 8.6 days, respectively; P <.0001). The percentage of pregnancies that delivered beyond term was significantly higher for male relative to female fetuses (26.5% vs 22.5% [P <.000001] at > or =41 weeks of gestation and 7.6% vs 5.5% [P <.000001] at > or =42 weeks of gestation, respectively). The weekly odds ratios for a delivery of a male fetus beyond term were 1.14, 1.39, and 1.50 at 41, 42, and 43 weeks, respectively. CONCLUSION: Male gender significantly predisposes to the prolongation of pregnancy to the extent that, by 43 weeks of gestation, there are 3 male deliveries for every 2 female deliveries.     

Prediction of lethal pulmonary hypoplasia and chorioamnionitis by assessment of fetal breathing

Summary. Twenty-three pregnancies with fetuses at risk for pulmonary hypoplasia were studied weekly until delivery. The amount of time spent in fetal breathing activity was recorded under controlled conditions during 1 h using real-time ultrasound. An amniotic fluid index was determined. The clinicians and the pathologist were unaware of the ultrasound findings. Eight of 23 fetuses did not breathe at the last ultrasound examination. Three babies died of pulmonary hypoplasia and two of these showed fetal breathing before birth. The three deaths were associated with rupture of the membranes at <20 weeks gestation and of ≥44 days duration. One infant developed bronchopulmonary dysplasia. The amniotic fluid index in these four pregnancies was low and the newborn infants had limb contractures. Chorioamnionitis/funisitis was noted in 13 placentas. Eight fetuses were assessed for fetal breathing within 2 days of birth. The lack of fetal breathing had sensitivity, specificity, positive and negative predictive values of 0.75 for chorioamnionitis/funisitis. In this pilot study the absence of fetal breathing was of no value in predicting lethal pulmonary hypoplasia, but was related to chorioamnionitis/funisitis. We recommend further studies of fetal breathing in relation to fetal/neonatal infections.     

Theory of obstetrics: An epidemiologic framework for justifying medically indicated early delivery

Background

Modern obstetrics is faced with a serious paradox. Obstetric practice is becoming increasingly interventionist based on empirical evidence but without a theoretical basis for such intervention. Whereas obstetric models of perinatal death show that mortality declines exponentially with increasing gestational duration, temporal increases in medically indicated labour induction and cesarean delivery have resulted in rising rates of preterm birth and declining rates of postterm birth. Other problems include a disconnection between patterns of gestational age-specific growth restriction (constant across gestation) and gestational age-specific perinatal mortality (exponential decline with increasing duration) and the paradox of intersecting perinatal mortality curves (low birth weight infants of smokers have lower neonatal mortality rates than the low birth weight infants of non-smokers).

Discussion

The fetuses at risk approach is a causal model that brings coherence to the various perinatal phenomena. Under this formulation, pregnancy complications (such as preeclampsia), labour induction/cesarean delivery, birth, revealed small-for-gestational age and death show coherent patterns of incidence. The fetuses at risk formulation also provides a theoretical justification for medically indicated early delivery, the cornerstone of modern obstetrics. It permits a conceptualization of the number needed to treat (e.g., as low as 2 for emergency cesarean delivery in preventing perinatal death given placental abruption and fetal bradycardia) and a calculation of the marginal number needed to treat (i.e., the number of additional medically indicated labour inductions/cesarean deliveries required to prevent one perinatal death). Data from the United States showed that between 1995–96 and 1999–2000 rates of labour induction/cesarean delivery increased by 45.1 per 1,000 and perinatal mortality decreased by 0.31 per 1,000 total births among singleton pregnancies at > = 28 weeks of gestation. The marginal number needed to treat was 145 (45.1/0.31), showing that 145 excess labour inductions/cesarean deliveries in 1999–2000 (relative to 1995–96) were responsible for preventing 1 perinatal death among singleton pregnancies at > = 28 weeks gestation.

Summary

The fetuses at risk approach, with its focus on incidence measures, provides a coherent view of perinatal phenomena. It also provides a theoretical justification for medically indicated early delivery and reconciles the contemporary divide between obstetric theory and obstetric practice.     

Prediction of lethal pulmonary hypoplasia and chorioamnionitis by assessment of fetal breathing

Twenty-three pregnancies with fetuses at risk for pulmonary hypoplasia were studied weekly until delivery. The amount of time spent in fetal breathing activity was recorded under controlled conditions during 1 h using real-time ultrasound. An amniotic fluid index was determined. The clinicians and the pathologist were unaware of the ultrasound findings. Eight of 23 fetuses did not breathe at the last ultrasound examination. Three babies died of pulmonary hypoplasia and two of these showed fetal breathing before birth. The three deaths were associated with rupture of the membranes at less than or equal to 20 weeks gestation and of greater than or equal to 44 days duration. One infant developed bronchopulmonary dysplasia. The amniotic fluid index in these four pregnancies was low and the newborn infants had limb contractures. Chorioamnionitis/funisitis was noted in 13 placentas. Eight fetuses were assessed for fetal breathing within 2 days of birth. The lack of fetal breathing had sensitivity, specificity, positive and negative predictive values of 0.75 for chorioamnionitis/funisitis. In this pilot study the absence of fetal breathing was of no value in predicting lethal pulmonary hypoplasia, but was related to chorioamnionitis/funisitis. We recommend further studies of fetal breathing in relation to fetal/neonatal infections.     

Ultrasound biometry of Arabian fetuses.

OBJECTIVE: To establish fetal ultrasound biometry charts for Arabian fetuses between 14 and 40 weeks of gestation. METHOD: Cross-sectional fetal ultrasound data of normal singleton pregnancies, which had been performed over a period of 7 years, were retrieved. Only pregnant Arab women with certain last menstrual period dates and/or early ultrasound examinations were included. Each fetus contributed to only one set of data. Normal ranges for biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were established. The mean and 5th and 95th percentiles at 18th, 28th, and 36 weeks of gestation were compared with similar ranges of published data from pregnancies of American and Anglo-Saxon population. RESULTS: Fetal ultrasound biometry has been established for our local population. Comparing our data with Western population emphasizes the presence of significant variation in fetal morphometric measurements, particularly in the later weeks of gestation and at the extremes of the range of fetal size. CONCLUSION: The clinical significance of this variation differs according to the primary objective of ultrasound fetal measurements. For estimation of fetal age, usually by head and femur measurements in early gestation, ethnic variation seems to have limited significance. Whereas for estimation of fetal growth and/or weight in the third trimester, based on abdominal circumference, the use of given points, e.g., 10th or 5th percentile derived from other population charts, has the potential of either over- or underdiagnosis of IUGR fetuses. The adoption of locally developed charts is recommended.     

Singleton pregnancy outcomes after assisted and non-assisted reproductive technology in infertile patients

Purpose

Singleton pregnancy after assisted reproductive technology (ART) has been associated with higher risks of adverse pregnancy outcome than naturally conceived singleton pregnancy. This study was to elucidate whether the ART procedure is responsible for abnormal pregnancy outcome comparing those after ART and non-ART in infertile patients.

Methods

We compare the singleton pregnancy outcome of infertile patients in our university hospital between 2000 and 2008 following ART (351 pregnancies) and non-ART (213 pregnancies) procedures. Pregnancy outcome parameters were incidence of pregnancy induced hypertension, placenta previa, placental abruption, cesarean delivery, preterm birth, very preterm birth, stillbirth, low birth weight and very low birth weight.

Results

Most of the pregnancy outcome parameters were not significantly different between the ART group and the non-ART group. Only placenta previa was significantly higher in the ART group than in the non-ART group (odds ratio 4.0; 95?% CI 1.2?C13.7).

Conclusions

ART procedure may itself be a risk factor for the development of placenta previa. Some of the abnormal perinatal outcomes that had been previously attributed to ART, however, may be due to the baseline characteristics of infertile patients.     

Placental histopathological findings in obese and nonobese women with complicated and uncomplicated pregnancies

Purpose

To investigate the role of placental abnormalities in complicated and uncomplicated pregnancies in obese women.

Methods

Placentas from patients with complicated or uncomplicated pregnancies and a pregravid body mass index (BMI) of ≥30?kg/m² were analyzed histopathologically for lesions consistent with maternal and fetal circulation abnormalities and inflammatory lesions related to the maternal or fetal response. Findings were compared with a normal-weight control group matched by mode of delivery and presence/type of pregnancy complications.

Results

The obese group consisted of 28 women of whom 46?% had a complicated pregnancy. The obese group had a higher rate of maternal inflammatory lesions than the normal-weight control group (43 vs. 3.6?%, p?<?0.001). There was no difference between the obese women with complicated and uncomplicated pregnancies in mean placental weight or lesions associated with fetal or maternal vascular supply.

Conclusion

Placental inflammatory lesions may underlie the worse pregnancy course of obese women relative to normal-weight women.     

Outcomes of pregnancies complicated by hyperemesis gravidarum

Objectives

To evaluate maternal and fetal outcomes among women with hyperemesis gravidarum (HG).

Methods

In a university hospital and a research and training hospital, a retrospective cohort study was conducted among women with singleton deliveries between 2003 and 2011. Maternal outcomes evaluated included gestational diabetes, pregnancy-induced hypertension, cesarean delivery. Neonatal outcomes also determined were 5-min Apgar score of less than 7, low birth weight, small for gestational age (SGA), preterm delivery, fetal sex, and stillbirth.

Results

There were no statistical differences in the mean of age, parity, the number of artificial pregnancy, and smoking between two groups. Infants from HG pregnancies manifested similar birth weight (3,121.5?±?595.4 vs. 3,164?±?664.5?g) and gestational age (38.1?±?2.3 vs. 38.1?±?2.6?weeks), relative to infants from the control group (p?=?0.67 and 0.91, respectively). In addition, no statistical significant differences were found in the rates of SGA birth, preterm birth, gestational diabetes, pregnancy-induced hypertension, and adverse fetal outcome between two groups (p?>?0.05). Cesarean delivery rates were similar in two groups (31.9% in hyperemesis group vs. 27% in control group, p?=?0.49). Comparing the gender of the newborn baby and Apgar scores less than 7 at 5?min, there were no statistically significant differences between two groups (p?=?0.16 and 0.42, respectively).

Conclusion

Hyperemesis gravidarum is not associated with adverse pregnancy outcomes.     

Is thrombophilia a risk factor for placenta-mediated pregnancy complications?

Purpose

To determine if thrombophilia is a risk factor for placenta-mediated pregnancy complications (PMPC) (i.e., preeclampsia, intrauterine growth restriction (IUGR), placental abruption, intrauterine fetal death and recurrent pregnancy loss).

Methods

A 5-year retrospective cohort study. Ongoing pregnancies in women with an antecedent PMPC with thrombophilia were compared with the pregnancies in similar women without thrombophilia. The main outcome measures were mean birth weight deviations, corrected for gestational age, and recurrence of PMPC. Low-molecular-weight heparin (LMWH) was employed for thromboprophylaxis only. Mann?CWhitney??s, Fisher??s and Chi-square tests were employed for comparison.

Results

PMPC recurred in 10/43 (23?%) in the thrombophilia group and in 7/41 (17?%) in the non-thrombophilia group, P?P?Conclusion Thrombophilia does hardly increase the risk of IUGR/PMPC or if so, it can be prevented by LMWH.     

Predicting delivery date by ultrasound and last menstrual period in early gestation

OBJECTIVE: To compare last menstrual period and ultrasonography in predicting delivery date. METHODS: We used ultrasound to scan 17,221 nonselected singleton pregnancies at 8-16 completed weeks. The last menstrual period (LMP) was considered certain in 13,541 and uncertain in 3680 cases. The duration of pregnancy from the scan to the day of spontaneous delivery was predicted by crown-rump length, biparietal diameter (BPD), and femur length (FL) using linear regression models, and the results were compared with estimates based on LMP. RESULTS: At all gestational ages, ultrasound was superior to certain LMP in predicting the day of delivery by at least 1.7 days. When deliveries before 37 weeks were excluded, crown-rump length measurement of 15-60 mm (corresponding to 8-12.5 weeks) had the lowest prediction error of 7.3 days. After that time, BPD (at least 21 mm) showed a similar error (7.3 days) and was more precise than crown-rump length. Femur length was slightly less accurate than crown-rump length or BPD. Regression models using a combination of any two or three ultrasonic variables did not improve accuracy of prediction. When ultrasound was used instead of certain LMP, the number of postterm pregnancies decreased from 10.3% to 2.7% (P <.001). CONCLUSION: Ultrasound was more accurate than LMP in dating, and when it was used the number of postterm pregnancies decreased. Crown-rump length of 15-60 mm was superior to BPD, but then BPD (at least 21 mm) was more precise. Combining more than one ultrasonic measurements did not improve dating accuracy.     

Prenatal diagnosis of β-thalassemia in Guangxi Zhuang Autonomous Region, China

Purpose

The aim of this study was to establish a comprehensive prenatal diagnosis service and to control the birth of thalassemia children in Guangxi Zhuang Automonous Region, China.

Methods

Prenatal diagnosis was performed in 1,058 couples with ‘at risk’ β-thalassemia from Guangxi Zhuang Automonous Region. Fetal samplings were collected by chorionic villus sampling in the first trimester, by amniocentesis in the second trimester and by cordocentesis in the third trimester. DNA analysis was carried out using polymerase chain reaction, reverse dot blot assay, multiplex ligation-dependent probe amplification method and DNA sequencing. Automated high-performance liquid chromatography system was used to analyze the fetal hemoglobin in pregnancies in case mutations were unidentified.

Results

A total of 12 different β-thalassemia mutations were characterized from 2,116 parents. The most common mutation for β-thalassemia was CD41–42 (-CTTT) followed by CD17 (A→T). Prenatal testing revealed 315 normal fetuses, 500 carriers and 253 β-thalassemia major fetuses. The couples having fetuses with β-thalassemia major were counselled to terminate the pregnancies. Postnatal follow-up confirmed all pregnancies.

Conclusion

Our prenatal diagnosis strategy proved to be highly effective in reducing severe thalassemia in pregnant populations.     

Good accuracy of ultrasound estimations of fetal weight performed by midwives

BACKGROUND: This study was undertaken to evaluate the quality of ultrasound estimation of fetal weight when performed by midwives experienced in ultrasound examinations. We also examined whether the accuracy was affected by fetal presentation, twin pregnancy or birth weight category. The results of 5 different formulas were compared to determine which was most accurate in our study population. METHODS: The study population consisted of 620 fetuses in 607 pregnancies, on whom fetal weight estimations had been performed within 3 days prior to delivery. The group of twins (n=27) was analysed separately. Results achieved by Hadlock 2 formula used in our unit were compared with 4 other widely used formulas for estimation of fetal weight. RESULTS: With Hadlock 2 formula, mean absolute percent error was 6.2% and SD of error was 7.6% of mean birth weight. A total of 81% of estimates were within 10% of the actual birth weight. All the formulas tended to overestimate the weight of twins and fetuses weighing <2,500 g, and underestimate the weight of fetuses >4,000 g. Presentation of the fetus did not significantly influence the accuracy. The formula Hadlock 2, using 3 parameters (biparietal diameter, abdominal circumference and femur length) gave the highest ICC of 0.910. CONCLUSIONS: Ultrasound estimation of fetal weight performed by midwives is feasible and of similar accuracy as in the original studies. Major errors may occur both in small and large birth weight groups.     

Neonatal outcome multiple pregnancies at the Neonatal Department of Research Institute of Polish Mother's Memorial Hospital

OBJECTIVES: The purpose of this study was to analyze the course of neonatal period among babies born from truly higher-order multiple pregnancies (> or = 3). DESIGN: The retrospective analysis included 81 infants born from multiple pregnancies (> or = 3), hospitalized in Neonatal Department of Research Institute of Polish Mother's Memorial Hospital between 1995-2001. MATERIALS AND METHODS: Studied population contained 63 babies delivered from 21 triplet pregnancies, 8 newborns from 2 quadruplet pregnancies and ten quintuplets. The groups were analyzed according to gestational age, birth weight, ventilation and hospitalization time as well as early and late consequences of prematurity. RESULTS: Among the multiples (> or = 3) the mean birth weight of triplets, quadruplets and quintuplets was respectively: 1656 g vs 1166 g vs 725 g, the diminished gestational age was also noticed: 32.4 vs 30 vs 26.5 GA. The cesarean section ratio in triplet deliveries was 95%, while quadruplets and quintuplets pregnancies were always delivered by operative interventions. The increase in number of fetuses was significantly associated with prolonged ventilation time (mean 9.5 vs 22.2 vs 57.5 days) as well as the hospitalization (mean 29.1 vs 64.1 s 79.6 days). The differences between mentioned above values reached statistical significance (p < 0.001). One out of three neonates born from triplet pregnancy required ventilatory support (36.6%), whereas in quadruplets and quintuplets this ratio reached 100%. The respiratory distress syndrome treated with surfactant was diagnosed in 7.9% (5/63) of triplets, 37.5% (3/8) quadruplets and 100% of quintuplets among whom 8 babies needed more than one dose of surfactant. The increased risk of unfavorable prematurity outcome (PDA, ROP, BPD, IVH) and neonatal death was highly related to plurality of pregnancy. CONCLUSIONS: Multiple pregnancies resulting from infertility treatment cause many medical problems. Undesirable outcome among neonates delivered from higher-order multiple pregnancies (> or = 3 fetuses) predestine to more judicious approach in the application of assisted reproductive techniques and multiple pregnancies prophylaxis.     

Earliest ultrasound findings and description of splicing mutations in Meckel–Gruber syndrome

Objective

To describe early ultrasound findings in Meckel–Gruber syndrome (MKS) in first and second trimester of three families, detailed ultrasound findings have been documented in addition to pathoanatomical findings and results of DNA studies. A splice site mutation in the MKS4 gene could be detected. Clinical management accounting risk assessment for future pregnancies is discussed and early ultrasound markers in MKS are described.

Methods

All cases were examined in a tertiary center for prenatal diagnosis by ultrasound. Necroscopy confirmed the clinical diagnosis. Fetal DNA analysis was accomplished in a reference center for MKS. In addition, ultrasound findings in early pregnancy of two further cases are described.

Results

Three couples presented with pregnancies complicated by MKS. The earliest diagnosis was suspected in 11?+?6?weeks of gestation and was confirmed in 13?+?0?weeks by ultrasound revealing a large occipital encephalocele and polycystic kidneys. Another case with recurrent MKS in two consecutive pregnancies was diagnosed in 20?weeks and 14?weeks of gestation, respectively. Here a close molecular genetic follow-up was performed leading to the detection of two mutations in the MKS4 gene in both fetuses. The third case was diagnosed in 15?weeks of gestation. Ultrasound findings in all pregnancies were doubtless and autopsies confirmed the diagnosis.

Conclusion

Detection of MKS is already possible in the first trimester. Knowledge of the underlying genetic defect helps counseling the couples with recurrence of MKS and chorionic villi sampling in the first trimester of pregnancy can be offered.     

Spontaneous reduction of multiple pregnancy: incidence and effect on outcome.

OBJECTIVE: Our objective was to determine the incidence of spontaneous reduction in multiple pregnancies during the first 12 gestational weeks and determine the outcome of the surviving fetuses. STUDY DESIGN: Analysis of prospectively collected ultrasound and birth information on 709 multiple and 5962 singleton pregnancies conceived at a private infertility clinic. RESULTS: Spontaneous reduction of one or more gestational sacs and or embryos occurred before the 12th week of gestation in 36% of twin (95% CI, 32%-40%), 53% of triplet (95% CI, 44%-61%), and 65% of quadruplet (95% CI, 46%-85%) pregnancies. Reduction was less frequent after ovulation induction than after spontaneous ovulation. In general, pregnancy duration and birth weight were inversely related to the initial gestational sac number irrespective of the final birth number. CONCLUSIONS: More than 50% of patients with 3 or more gestational sacs had spontaneous reduction before 12 weeks. The surviving fetuses weighed less and were born earlier than unreduced pregnancies with the same initial number of fetuses.