Background: In extremely severe Rh (D) alloimmunization, during pregnancy, early diagnosis and treatment is essential to avoid hydrops fetalis. Intrauterine transfusion (IUT) is of utmost importance in the prevention of fetal anemia but it is usually feasible only after 20 weeks of pregnancy. Therefore, additional treatment options in early pregnancy are needed.Study design and inethods: A 27-year-old severely D + C immunized woman was admitted at 8 weeks of gestation in her fifth pregnancy with an extremely high concentration of anti-D. Her first pregnancy was uneventful but resulted in D + C allo immunization. The next two pregnancies were unsuccessful, because of hydrops fetalis resulting in fetal death in pregnancy week 20 and 24, respectively, despite treatment with high-dose intravenous immunoglobulin (IVIG) and IUT treatment. A fourth pregnancy was terminated with legal abortion.The patient was eager and persistent to accomplish a successful pregnancy. Therefore, a combination of treatments consisting of plasma exchange (PE) three times/week and IVIG 100 g/week was started in pregnancy week 12. PE was performed 53 times and totally 159 L of plasma was exchanged.Results: The anti-D concentration was 12 mu g/mL (IAT titer 2000) before start of treatment by PE and IVIG in pregnancy week 12. The concentration of anti-D was gradually reduced to approximately 3 mu g/mL after only two weeks of treatment and was maintained at that level until pregnancy week 22.In pregnancy week 26 and 27, signs of hydrops were detected by ultrasonography and IUT were performed at each occasion. Sectio was inevitable at pregnancy week 28 + 1 and a male baby was born: Hb 58 g/L (cord sample) and 68 g/L (venous sample); weight 1385 g; Apgar score = 4-5-7; Bilirubin 56-150 mmol/L (4 h). Exchange transfusion was performed on day two and day five. Phototherapy was also implemented for eight days. The newborn's recovery thereafter was uneventful and complete.Conclusion: A combination of PE and IVIG may be an efficient treatment possible to start in early pregnancy in patients with extremely severe Rh (D) alloimmunization, with a history of hydrops fetalis in previous pregnancies. (c) 2006 Elsevier Ltd. All rights reserved.

Background. To determine the detection rate of fetal structural abnormalities by a routine 11-14-week ultrasound scan for dating in an unselected pregnant population. Methods. A prospective observational cohort study of 2,708 unselected pregnant women attending an abdominal ultrasound examination at 11-14 weeks gestation. The number of major fetal structural abnormalities diagnosed after birth was obtained from a computerized database at the same unit. Results. Out of 2,708 pregnant women, 89 (3.3%) were found to have a missed abortion at the time of the ultrasound scan and 33 (1.2%) were diagnosed as twins. Thirteen major structural abnormalities were detected, three cases of anencephaly (one case also had a spina bifida), one case with hydranencephaly, one fetus with Dandy-Walker syndrome, two cases with gastroschisis, one case with a bilateral hydronephrosis, one case with a generalized hydrops, one fetus with multiple malformations, and three cystic hygromas. An additional 19 major structural defects were detected at birth. Four cases of neural tube defects and nine fetuses with congenital heart defects were diagnosed. The antenatal ultrasound detection rate was 40.6% (13/32). Nine patients had a nuchal translucency greater than 3.0 mm (excluding cystic hygromas); two of them had chromosomal abnormalities (trisomy 21 and trisomy 18). Conclusions. Fetal structural abnormalities were detected in 41% (95% CI = 24-59) of the cases in an unselected pregnant population at a routine 11-14-week ultrasound scan for dating purpose. Two out of nine fetuses with a nuchal translucency greater than 3.0 mm had a chromosomal abnormality.

Background. To determine the detection rate of fetal structural abnormalities by a routine 11–14-week ultrasound scan for dating in an unselected pregnant population. Methods. A prospective observational cohort study of 2,708 unselected pregnant women attending an abdominal ultrasound examination at 11–14 weeks gestation. The number of major fetal structural abnormalities diagnosed after birth was obtained from a computerized database at the same unit. Results. Out of 2,708 pregnant women, 89 (3.3%) were found to have a missed abortion at the time of the ultrasound scan and 33 (1.2%) were diagnosed as twins. Thirteen major structural abnormalities were detected, three cases of anencephaly (one case also had a spina bifida), one case with hydranencephaly, one fetus with Dandy-Walker syndrome, two cases with gastroschisis, one case with a bilateral hydronephrosis, one case with a generalized hydrops, one fetus with multiple malformations, and three cystic hygromas. An additional 19 major structural defects were detected at birth. Four cases of neural tube defects and nine fetuses with congenital heart defects were diagnosed. The antenatal ultrasound detection rate was 40.6% (13/32). Nine patients had a nuchal translucency greater than 3.0 mm (excluding cystic hygromas); two of them had chromosomal abnormalities (trisomy 21 and trisomy 18). Conclusions. Fetal structural abnormalities were detected in 41% (95%CI = 24–59) of the cases in an unselected pregnant population at a routine 11–14-week ultrasound scan for dating purpose. Two out of nine fetuses with a nuchal translucency greater than 3.0 mm had a chromosomal abnormality.

In the past 20 years, a significant improvement has been shown in the treatment for infertility in both women and men through the development of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Only donated sperm could be previously used for treatment; now oocytes can also be donated. Furthermore, the combination of IVF and ICSI with advanced genetic methods has made preimplantation genetic diagnosis possible for many genetic conditions. These methods enable genetic testing of the early human embryo by using only a single cell, one blastomere biopsied from the embryo, as the sample from which the diagnosis of many chromosome rearrangements and other inherited diseases can be made. It has also been established that a considerable proportion of infertility is caused by genetic defects, which have several implications for infertility treatment. The purpose of this review is to give a concise introduction on how genetics is involved in assisted reproduction technology to specialists who may not be working in this particular field of gynecology, but who would need some knowledge of this for proper care of their patients.

PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with intravenous immunoglobulin (IVIG).METHOD OF STUDY: Forty-one women with a history of unexplained RSA were examined during first trimester of pregnancy before IVIG or placebo treatment and after pregnancy. The results were compared with five healthy, non-pregnant women and five women in the first trimester of normal pregnancy. Circulating lymphocyte subsets with focus on T-cell subpopulations were determined by flow cytometry.RESULTS: The proportions of human leukocyte antigen (HLA)-DR positive T cells (CD3 + HLA-DR +), T-killer/effector cells (CD8 + S6F1 +) and B cells (CD 19 +) were increased, whereas the proportion of T-suppressor/inducer cells (CD4 + CD45RA +) was decreased during first trimester pregnancy of RSA women compared with pregnant normal controls. T and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG or placebo group.CONCLUSIONS: In RSA patients, the immune system seems to be activated in contrast to the suppression noted in normal pregnancy.

PROBLEM: To study whether the occurrence of mixed lymphocyte culture (MLC) blocking antibodies is associated with pregnancy outcome in women with unexplained recurrent spontaneous abortion (RSA) and the in vivo effect of intravenous immunoglobulin (IVIG) treatment on MLC blocking effect.METHOD OF STUDY: Blood samples from 41 RSA patients were obtained before and after pregnancy, and blocking antibodies were estimated by one-way MLC assay. The patients received IVIG or placebo (saline) during pregnancy. Additionally, prepregnancy blood samples from 31 RSA women and 10 controls were obtained.RESULTS: We found no correlation between blocking antibodies before pregnancy and the pregnancy outcome. The occurrence of blocking antibodies was not affected by pregnancy or IVIG treatment.CONCLUSIONS: Blocking antibodies have no predictive value for the pregnancy outcome in RSA patients, and their production seems not to be affected by IVIG.

A healthy primigravida had moderate polyhydramnion (amniotic fluid index (AFI) = 230 mm) at 32 gestational weeks. The fetus had dilated, fluid filled, and frequently contracting small bowels filling the whole abdomen (figs 1 and 2), most likely representing distal small bowel atresia or stenosis. At 33 weeks, increasing polyhydramnion (AFI = 430 mm) led to the aspiration of 1180 ml of clear amniotic fluid not stained with meconium. At 36 weeks, the patient had an uneventful spontaneous delivery of …

The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin (IVIG) in the prevention of recurrent spontaneous abortion (RSA). In a double-blind, randomized, placebo-controlled study, 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy. The birth of a child was considered a successful outcome. The overall success rate was 77% in the IVIG group compared with 79% in the placebo group. For women with primary RSA the success rates were 82 (IVIG) and 89% (placebo), and for women with secondary RSA the rates were 73 (IVIG) and 70% (placebo). We found no statistically significant difference in treatment results between IVIG and placebo.

Background. Maternal serum anti-D is actively transported across the placenta into the fetal blood where it adheres to D-positive erythrocytes. The anti-D coated red cells attach to Fc-receptors on fetal reticuloendothelial cells and are subsequently phagocytosed and hemolysed. It is not known if anti-D is consumed or recirculated in this process. Main question. Is anti-D in the fetus consumed in the hemolytic process in the erythroblastotic fetus and can the consumption be modulated by high-dose immunoglobulins (IVIG) given to the mother?Methods. Fetal/maternal serum anti-D concentration ratios were calculated for simultaneously taken blood samples from three groups of Rh(D) immunized pregnant women; six women with fetuses who were of Rh(D) negative phenotype, 19 women with fetuses who were Rh(D) positive and received no treatment and, seven women who were treated with IVIG because they bore anemic, Rh(D) positive fetuses.Results. Fetuses with a Rh(D) negative phenotype expressed an increase in fetal/maternal anti-D concentration ratios from 10 to 55% between 25 and 31 gestational weeks, while Rh(D) positive fetuses without IVIG treatment had stable values at the 10% level between 24 and 35 gestational weeks. During IVIG-treatment of the mothers, Rh(D) positive fetuses showed an increase in ratio from 10 to 30% between 26 and 34 gestational weeks. There was a statistically significant (p<0.001) difference between regression results of the three groups.Conclusions. Fetal anti-D is consumed in the hemolytic process and the consumption can be modulated by IVLG given to the mother.

PROBLEM:How does the placental transport of immunoglobulin G (IgG) vary with gestational age?METHOD OF STUDY:MEDLINE was searched for the appearance of "pregnancy" and "IgG" in the title or abstract from 1966 up to 1995. All publications were reviewed for any kind of IgG data from the fetus and the mother and "known" gestational age. In total, 96 publications from the MEDLINE search fulfilled the search criteria. Seven of ninety-six publications contained IgG and gestational age data from the fetus and/or the mother. Five other publications that fulfilled the same criteria were also available and were also included.RESULTS:Fetal serum IgG concentrations were found to increase with gestational age according to the formula: fetal IgG = 13.564 - 1.094 x gestational age (GA) + 0.026 x GA2 (R2 = 0.877). The fetomaternal (f/m) ratio was also found to increase with gestational age according to the formula: f/m IgG = 0.399 - 0.059 x GA + 0.003 x GA2 - 2.065 x 10(-5) x GA3 (R2 = 0.831).CONCLUSIONS:The fetal IgG concentrations exceed maternal IgG concentrations after the 35th week of pregnancy. The fetal IgG concentrations are extremely low in the beginning of pregnancy, they exceed 2.5 g/L at > 25 pregnancy weeks, and they reach 5 g/L at pregnancy week 30.

PROBLEM: The following questions were addressed: Is the placental transport of immunoglobulin (Ig)G, IgG1, and IgG3 diminished in pregnancies at risk of hemolytic disease of the newborn? Is the placental transport of IgG, IgG1, and IgG3 correlated with the hemoglobin concentration in the fetus and AutoAnalyzer (AA) quantitations of maternal anti‐D?METHOD OF STUDY: IgG concentrations were determined retrospectively in 41 paired fetal/maternal (f/m) samples in 31 Rh (D) alloimmunized pregnancies. IgG1 and IgG3 concentrations were determined in those 23 cases in which the results of fetal hemoglobin concentration and quantitations of maternal anti‐D were available. The results were compared with values found in normal pregnancy and correlated with maternal anti‐D AA quantitations and fetal hemoglobin concentrations.RESULTS: Fetal IgG, IgG1, and IgG3 concentrations, and the corresponding fetomaternal ratios in Rh (D) alloimmunized pregnancies, increased with gestational age according to the following formulas (obtained by simple regression): Fetal IgG = −8.846 + 0.491.gestational age (GA), (R2 = 0.544); fetal IgG1 = −10.021 + 0.46GA, (R2 = 0.463); fetal IgG3 = −0.865 + 0.039GA, (R2 = 0.327); f/m IgG = −1.006 + 0.054−GA, (R2 = 0.557); f/m IgG1 = −1.876 + 0.085GA, (R2 = 0.654); f/m IgG3 = −0.199 + 0.026GA, (R2 = 0.146).CONCLUSIONS: The placental transport of IgG, IgG1, and IgG3 in women with Rh (D) immunizations is not diminished compared with normal pregnancy. However, AA quantitations of anti‐D are inversely correlated with f/m IgG ratio, f/m IgG1 ratio, and fetal IgG and IgG1 concentrations (P = 0.002, P = 0.004, P = 0.02, and P = 0.02 respectively).The placental transport of IgG3 is significantly higher in pregnancies at risk of hemolytic disease of the newborn compared with IgG3 concentrations in normal pregnancy.

BACKGROUND:To evaluate the implementation of nuchal translucency measurement as an additional examination within the first trimester routine ultrasound in an unselected population of women.METHODS:A prospective study in which all pregnant women during 1994, referred for the first trimester routine ultrasound scan, were asked to participate. Of a total of 1852 women with a viable pregnancy, results from 1444 women were evaluated. When a nuchal translucency of 4 mm or more was found, the woman was offered both a genetic amniocentesis in gestational week 13-15 and an additional ultrasound examination in gestational week 18-19.RESULTS:Six fetuses had a nuchal translucency of 4 mm or more and none of these had any chromosomal abnormality. Neither had any of the fetuses in the study, karyotyped for other reasons, any chromosomal defect and nor was there any child born with aneuploidy in the study population. No strong relation between major malformations e.g. abnormalities of the heart and increased nuchal translucency was found. The fetus with the largest nuchal translucency (=6 mm) was born healthy.CONCLUSION:The efficacy of nuchal translucency measurement needs further evaluation before it can be introduced as a screening method in an unselected pregnant population.

Available standard intrauterine growth curves based on birthweights underestimate foetal growth in preterm period. New growth curves are presented based on data from four Scandinavian centres for 759 ultrasonically estimated foetal weights in 86 uncomplicated pregnancies. Mean weight of boys exceeded that of girls by 2‐3%. A uniform SD value of 12% of the mean weight was adopted for the standard curves as the true SD varied non‐systematically between 9.1 and 12.4%. Applied to an unselected population of 8663 singleton births, before 210 days of gestation, 32% of birthweights were classified as small‐for‐gestational age (SGA; i.e. below mean ‐2SD); the corresponding figures were 11.1% for gestational ages between 210 and 258 days, and 2.6% for ages of 259 days or longer. The new growth curves reveal better the true distribution of SGA foetuses and neonates, and are suggested for use in perinatological practice.

Background. High dose intravenous immunoglobulin has been reported to be advantageous in the treatment of alloimmunization during pregnancy. The mode of action is unknown.Method. High dose intravenous immunoglobulin was used as the sole prenatal treatment in six severely rhesus(D) sensitized pregnant women. Maternal and fetal anti-D concentrations as well as fetal hemoglobin concentrations were studied. Seven pregnancies in rhesus(D) sensitized women served as controls. They received no treatment because they had milder forms of erythroblastosis fetalis or, in one case, a rhesus(D) negative fetus.Result. No obvious inhibitory effect of the treatment on maternal anti-D production and transplacental anti-D passage to the fetus was found. The fetal hemoglobin concentrations remained stable at about 80 g/L (hematocrit 27%) in five of six treated patients while there was a significant decrease in the control group.Conclusion. High dose intravenous immunoglobulin treatment seems to act mainly on fetal red cell destruction rate, possibly by blocking Fe receptor mediated macrophage phagocytosis. We claim that the treatment can successfully be used to prevent further deterioration of fetal anemia in rhesus(D) immunizations if started before severe fetal anemia (hemoglobin concentration <70 g/L, hematocrit <23%) and imminent hydrops fetalis arises.

Rockall TA, Logan RFA, Devlin HB, Northfield TC