Török O

Perinatal outcome in grand and great-grand multiparity: Effects of parity on obstetric risk factors

OBJECTIVE We sought to compare obstetric and neonatal complications among great-grand multiparous, grand multiparous, and multiparous women. STUDY DESIGN One hundred thirty-three great-grand multiparas, 314 grand multiparas, and 2195 multiparas who were delivered of their infants between 1988 and 1998 were selected for the study. To facilitate comparison, the patients were all >35 years old and had similar socioeconomic characteristics. RESULTS The incidence of malpresentation at the time of delivery, maternal obesity, anemia, preterm delivery, and meconium-stained amniotic fluid increased with higher parity, whereas the rate of excessive weight gain and cesarean delivery decreased. Compared with grand multiparas, great-grand multiparas had significantly elevated risks for abnormal amounts of amniotic fluid, abruptio placentae, neonatal tachypnea, and malformations but lower rates of placenta previa (P <.05). The incidence of postpartum hemorrhage, preeclampsia, placenta previa, macrosomia, postdate pregnancy, and low Apgar scores was significantly higher in grand multiparas than in multiparas, whereas the proportion of induction, forceps delivery, and total labor complications was significantly lower than in the multiparous group (P <.05). Similar frequency of maternal diabetes, infection, uterine wall scar rupture, variations in fetal heart rate, fetal death, and neonatal mortality was found in the 3 groups. CONCLUSION Both high-parity groups have their own risk factors, but the rate of some complications decreases with higher parity. In addition, perinatal mortality remains low in these patients, and therefore, under satisfactory socioeconomic and health care conditions, high parity should not be considered dangerous.

Multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction, except for very-high-order multiples

OBJECTIVE Our purpose was to investigate whether multifetal pregnancies reduced to twins have an increased risk of intrauterine growth restriction and discordant birth weight. STUDY DESIGN This retrospective cohort study investigated the rates of birth weight discordance > 20% and intrauterine growth restriction using both twin and singleton birth weight curves in 441 twin deliveries after multifetal pregnancy reduction (233 reduced from triplets, 156 from quadruplets, and 52 from quintuplets or greater) compared with 136 nonreduced dichorionic twins. RESULTS No significant difference was found in the frequency of birth weight discordance and in the overall incidence of intrauterine growth restriction by both twin and singleton birth weight curves when pregnancies that underwent multifetal pregnancy reduction were compared with the control group. There was, however, an almost twofold increase in the rate of intrauterine growth restriction in pregnancies with a starting fetal number of 5 or more (23.1%) compared with that in those reduced from triplets or quadruplets (12.1%) when the twin curve standard was used (P = .03). This difference disappeared when these groups were compared with a singleton nomogram. CONCLUSION This study suggests that multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction unless the starting fetal number is > or = 5. This finding provides a further rationale to avoid transferring excessive numbers of preembryos after in vitro fertilization.

Risk of Recurrence of Craniospinal Anomalies

The authors analyzed 1,655 situations from their Genetic Counseling Service over a 15 year period where the reason for counseling was craniospinal anomaly (neural tube defects and/or hydrocephalus) in the family. Excluding the obviously monogenically inherited cases, they investigated pregnancies undertaken after 1,285 isolated and 177 multiple forms of craniospinal abnormalities. The recurrence rate of craniospinal defects was found to be 3.66%, which is about ten times higher than the general population risk, supporting the theory of the multifactorial threshold model in the inheritance of these anomalies. The recurrence risks of neural tube defects and of hydrocephalus were 3.47% and 2.95%, respectively. The authors concluded that recurrence risk is mainly influenced by the pathoanatomic severity of the involved anomaly, the degree of relationship, and the number of affected relatives in the family. There is a positive correlation between the pathoanatomic severity of the anomaly in the proband and the offspring. At least in one-half of the cases the same type of anomaly was observed again in the offspring as in the proband. Attention is drawn to the fact that hydrocephalus (ventriculomegaly) is often manifested only in the second half of gestation. Therefore, performing ultrasound examination is strongly recommended not only at the 18th but at the 24th week of gestation, as well in pregnancies with a positive history of neural tube defects and/or hydrocephalus.

Prenatal diagnosis of cystic fibrosis by trehalase enzyme assay in amniotic fluid

Amniocentesis and amniotic fluid trehalase enzyme assay were offered to 14 pregnant women at a 1 in 4 risk for a child with cystic fibrosis. Twelve of these pregnancies were screened at the 18th week of gestation; ten proceeded to term, seven following the finding of a normal trehalase activity and three despite the low enzyme level in amniotic fluid. In all ten cases prenatal diagnosis proved to be correct. In two cases with low enzyme activity parents opted for termination at the 19th week, and with PAS‐Alcian Blue staining some slight histochemical lesions characteristic of cystic fibrosis were seen in the exocrine glands, including the pancreas and intestinal mucosa, of both fetuses. The total protein content in the meconium of these fetuses was significantly higher than in the controls.

Genetic amniocentesis after multifetal pregnancy reduction

OBJECTIVE Our purpose was to evaluate the pregnancy loss rate resulting from genetic amniocentesis after multifetal pregnancy reduction. STUDY DESIGN A cohort study was performed in pregnancies with maternal age >30 years. Pregnancy loss in a study population of 127 patients who underwent genetic amniocentesis after multifetal pregnancy reduction were compared with a control group of 167 patients who did not have genetic amniocentesis after multifetal pregnancy reduction. RESULTS The pregnancy loss rate in patients who underwent genetic amniocentesis after multifetal pregnancy reduction was 3.1% (4/127 cases) compared with 7.2% (12/167 cases) in the controls (P >.05). In the study group evidence of infection was found in only 1 case, in which the pregnancy loss occurred 1 day after the amniocentesis. In the other cases the pregnancy losses occurred 5 weeks after genetic amniocentesis, and these losses could not be directly attributed to either genetic amniocentesis or the multifetal reduction procedure. CONCLUSION Our data suggest that the performance of genetic amniocentesis after multifetal pregnancy reduction does not increase the risk of pregnancy loss over that observed in association with the reduction itself.

In utero incarceration of congenital diaphragmatic hernia.

In utero diagnosis of incarcerated congenital diaphragmatic hernia has never been reported. In our case, congenital diaphragmatic hernia presented at 34 weeks of gestation with dilated bowel loops, pleural effusion, and ascites on fetal ultrasound. Preterm delivery and emergency exploration revealed a tight posterolateral diaphragmatic defect with extensive bowel infarction.

Mutational Spectrum of Smith-Lemli-Opitz Syndrome Patients in Hungary

Smith-Lemli-Opitz (SLO) syndrome is an autosomal recessive disorder characterized by multiple congenital abnormalities and mental retardation. The condition is caused by the deficiency of 7-dehydrocholesterol reductase (DHCR7) which catalyzes the final step in cholesterol biosynthesis. Biochemical diagnosis is based on increased concentration of 7-dehydrocholesterol (7-DHC) in the patient serum. Both life expectancy and quality of life are severely affected by the disease. The estimated prevalence of SLO syndrome ranges between 1:20,000 and 1:40,000 among Caucasians. Although the mutational spectrum of the disease is wide, approximately 10 mutations are responsible for more than 80% of the cases. These mutations show a large interethnic variability. There are no mutation distribution data from Hungary to date. Thirteen patients were diagnosed with SLO syndrome in our laboratory. As first-line tests, serum 7-DHC and total cholesterol were measured and, in positive cases, molecular genetic analysis of the DHCR7 gene was performed. Complete genetic background of the disease could be identified in 12 cases. In 1 case only 1 mutation was detected in a heterozygote form. One patient was homozygous for the common splice site mutation c.964–1G>C, while all other patients were compound heterozygotes. One novel missense mutation, c.374A>G (p.Tyr125Cys) was identified.

Measuring expression levels of small regulatory RNA molecules from body fluids and formalin-fixed, paraffin-embedded samples

MicroRNAs are involved in the regulation of various pathophysiological processes such as immune regulation and cancer. Next-generation sequencing methods enable us to monitor their presence in various types of samples but we need flexible methods for validating datasets generated by high-throughput methods. Here we describe the detailed protocols to be used with our MiRNA Primer Design Tool assay design system. The presented methods allow the flexible design of the oligonucleotides needed for the RT-qPCR detection of any variant of small regulatory RNA molecules from virtually any species. This method can be used to measure miRNA levels from formalin-fixed, paraffin-embedded (FFPE) samples and various body fluids. As an example, we show the results of the hsa-miR-515-3p, hsa-miR-325, and hsa-miR-155 quantification using a specific UPL probe (Universal Probe Library) and a stem-loop RT-qPCR assay. The small nucleolar RNA RNU43 is used as endogenous control for normalization of the results. Urine from healthy pregnant women and FFPE samples from patients diagnosed with colorectal cancer and treated with antibody-based anti-EGFR monotherapy were used as samples.

Molecular Diagnostic Challenges and Complex Management of Consecutive Twin Pregnancies in a Family with CD40 Ligand Deficiency.

X‐linked hyper‐IgM syndrome (XHIGM) is a primary immunodeficiency disorder (PID) caused by mutation in the gene encoding the CD40 ligand (CD40L) expressed on activated T cells. Prenatal genotyping in carriers with twin pregnancies is more challenging than in women with singleton pregnancies. In addition, women with twin pregnancies may decide on selective termination for which the risk of loss of the healthy foetus may exceed 7%. We report here on a family affected by XHIGM. Diagnosis of the disease was made in a male patient as late as 33 years of age. After family screening, the sister of the proband conceived male twins in two consecutive pregnancies. In the first pregnancy, one of the male foetuses was hemizygous for the c.521A>G (Q174R) mutation in the CD40L gene. In the second pregnancy, ultrasound scan showed one foetus to have exencephaly and karyotyping revealed this foetus to have trisomy 18. Several options were discussed, but the parents decided on selective termination in both pregnancies. The interventions were successful in both cases, and the mother now has two healthy sons. This report demonstrates the way in which advanced technologies in molecular medicine and obstetric interventions may assist families with decisions about possible selective termination in case of life‐threatening molecular or chromosomal disorders. Diagnosis of CD40L deficiency at the age of 33 years in the proband was striking and indicated that PIDs are still neglected as disease entities in the evaluation of patients with recurrent severe infectious diseases.

Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply

Abstract Pregnant women are prone to iodine deficiency due to the increased need for iodine during gestation. Progress has recently occurred in establishing serum thyroglobulin (Tg) as an iodine status biomarker, but there is no accepted reference range for iodine sufficiency during pregnancy. An observational study was conducted in 164 pregnant women. At week 16 of gestation urinary iodine concentration (UIC), serum Tg, and thyroid functions were measured, and information on the type of iodine supplementation and smoking were recorded. The parameters of those who started iodine supplementation (≥150 μg/day) at least 4 weeks before pregnancy (n = 27), who started at the detection of pregnancy (n = 51), and who had no iodine supplementation (n = 74) were compared. Sufficient iodine supply was found in the studied population based on median UIC (162 μg/L). Iodine supplementation ≥150 μg/day resulted in higher median UIC regardless of its duration (nonusers: 130 μg/L vs. prepregnancy iodine starters: 240 μg/L, and pregnancy iodine starters: 205 μg/L, p < .001, and p = .023, respectively). Median Tg value of pregnancy starters was identical to that of nonusers (14.5 vs. 14.6 μg/L), whereas prepregnancy starters had lower median Tg (9.1 μg/L, p = .018). Serum Tg concentration at week 16 of pregnancy showed negative relationship (p = .010) with duration of iodine supplementation and positive relationship (p = .008) with smoking, a known interfering factor of iodine metabolism, by multiple regression analysis. Serum Tg at week 16 of pregnancy may be a promising biomarker of preconceptual and first trimester maternal iodine status, the critical early phase of foetal brain development.