Gundula Hebisch

Aberrant positioning of trophoblast and lymphocytes in the feto-maternal interface with pre-eclampsia

Abstract Pregnancy represents the growth of an allograft where fetal trophoblast cells evade immune rejection and invade maternal tissue. There should be a balance between fetal trophoblast and maternal immune-responsive cells and alterations in the proportion of these cells may relate to pregnancy disorders. To test this, the decidual tissue of placental bed biopsies was examined and trophoblast cells and lymphocytes were quantified morphometrically; spiral arteries were classified as unchanged, transformed or affected by acute atherosis. Normal pregnancy (n=19) was characterized by the transformation of about one half of all spiral arteries within the placental bed. We found that 40% of all lymphocytes were CD56+ uterine NK cells and 60%, CD3+ T-lymphocytes; about 30% of these were CD8+ T cells. Intrauterine growth retardation in the context of preeclampsia (n=15) was accompanied by reduced trophoblast numbers within smaller and more tortuous arteries and an increase in the proportion of CD56+ uterine NK cells and CD8+ T lymphocytes in the decidua (70% of all CD3+ cells). In the case of pre-eclampsia without fetal growth retardation (n=14) no increase in CD56+ uterine NK cells was seen, while CD8+ T lymphocytes were significantly increased compared with the normal level (50% of all CD3+ cells). Fetal growth retardation is associated with poor transformation of spiral arteries and characterized by an increase of uterine NK cells. Symptoms of pre-eclampsia are independently associated with an increase in the cytotoxic T subset of decidual lymphocytes. Pre-eclampsia and related fetal growth retardation are seemingly caused by an enhancement of the maternal cytotoxic defence against the fetal allograft.

Methadone maintenance program in a Swiss perinatal center: (I): Management and outcome of 89 pregnancies

Background.  Although methadone maintenance is the standard treatment of opiate addiction in pregnancy, opinion as to its utility is divided. The aim of this study was to analyze polydrug abuse, pregnancy outcome and fetomaternal complications among pregnant women in a major Swiss methadone maintenance program.

Vaginal uterine artery ligation avoids high blood loss and puerperal hysterectomy in postpartum hemorrhage

OBJECTIVE To describe a novel, effective, and minimally invasive surgical technique for avoiding excess blood loss and hysterectomy in intractable postpartum hemorrhage. Previously described techniques—uterine artery ligation at various levels, hypogastric (internal iliac) artery ligation, uterine compression—all require an abdominal approach. METHODS This procedure, which is quickly learned, is performable in the delivery room with minimal preparation, with or without bladder retraction. A 2‐cm horizontal incision is made in the anterior cervix 1 cm beneath the estimated vaginocervical fold and the bladder reflected in the natural plane. Firm but gentle downward traction on the uterus to the contralateral side of the intended ligature maximizes cephalad and lateral access, permitting bilateral uterine artery ligation from laterally under direct vision and/or indirect transcervical palpation. RESULTS Between November 1997 and June 2001, 13 women with intractable postpartum hemorrhage chose the vaginal route over laparotomy as a uterus‐preserving procedure. Hysterectomy proved necessary in only one case (8%) because of placenta percreta. One woman has since delivered a healthy term infant by cesarean, and uterine vascularization was unimpaired. CONCLUSION The vaginal route offers a novel, simple, effective, and minimally invasive technique for treating intractable puerperal hemorrhage by uterine artery ligation. Timely intervention avoids hysterectomy and consumption coagulopathy and preserves reproductive potential.

Seven cases of Wiedemann‐Beckwith syndrome, including the first reported case of mosaic paternal isodisomy along the whole chromosome 11

Genomic imprinting of chromosome arm 11p is involved in the Wiedemann-Beckwith syndrome (WBS). About 20% of patients with sporadic WBS have paternal uniparental disomy (UPD) of 11p. Mitotic recombination at the 11p region has been suggested to be responsible for the somatic mosaicism in these patients. Our current study concerning sporadic WBS patients demonstrated six patients with mosaic isodisomy restricted to part of 11p and one patient with mosaic paternal uniparental disomy for the whole chromosome 11. Apparently the clinical findings for this patient did not differ from data reported for other WBS patients. This case makes it unlikely that the proximal short arm and the long arm of chromosome 11 contain imprinted genes with a phenotype recognizable prenatally or in infancy, and gives some support to the hypothesis that non-mosaic UPD-11 is prenatally lethal.

The relationship between cervical dilatation, interleukin-6 and interleukin-8 during term labor

Background. To determine interleukin‐6 and interleukin‐8 levels in amniotic fluid, retroplacental blood and maternal serum and relate these values with cervical dilatation in term labor.

Maternal serum interleukin-1β, -6 and -8 levels and potential determinants in pregnancy and peripartum

Abstract Aims: To measure maternal serum interleukins (IL) in pregnancy, delivery and early puerperium, and to identify their potential determinants. Methods: Prospective longitudinal measures of serum IL-1β, IL-6 and IL-8 in 38 healthy pregnant women at antenatal visits, through labor and delivery, with clinical correlates (infection, vaginal hemorrhage and anemia) recorded by questionnaire. Results: Pregnancy IL levels remained consistently low. IL-1β increased shortly before delivery, then returned to pregnant levels, except where blood loss exceeded 500 ml. IL-6 and IL-8 rose at labor onset and exceeded pregnancy levels through postpartum day three. Postpartum IL-6 was higher after non-elective cesarean section than after spontaneous delivery (P < 0.0001), and where blood loss exceeded 500 ml. IL-6 and IL-8 were higher with systemic infection during delivery (P < 0.0001) and on postpartum day one (P < 0.05); IL-8 was higher in anemia (delivery: P < 0.005; postpartum day 1: P < 0.05). Differences due to delivery mode and systemic infection remained significant after correction for other conditions. Conclusions: Labor-dependent inflammation increases all IL levels at delivery. Further studies with larger sample sizes are required to establish reference values differentiating physiology from pathology as an aid to peripartum management.

Placental pathology: its impact on explaining prenatal and perinatal death

This review considers six main situations in which pathologists are expected to report and interpret placental messages for obstetricians, neonatologists and, indirectly, parents: (1) abortion is the body’s corrective response to the embryonic defect suggested by malformed chorionic villi; (2) infection causing chorionic villous inflammation is specific and haematogenous; pathogen identification is mandatory, in contrast to chorioamnionitis caused by increased local immunosuppression allowing indiscriminate bacterial entry; (3) prematurity and (4) intrauterine growth restriction are often associated with pregnancy-specific disease (pre-eclampsia) or pre-existing maternal conditions (systemic lupus); parental studies may improve outcome in subsequent pregnancies; (5) intrauterine death near term is often due to placental dysmaturity featuring a severely reduced number of syncytiocapillary membranes; it accounts for the death in utero of 3 in 1000 pregnancies; detection helps to minimise recurrence in subsequent pregnancies; (6) twins are best confirmed as monozygous by the absence of chorionic tissue in the dividing membranes; most monochorionic twins have vascular connections whose detailed analysis is requested only if there are inter-twin differences in growth and colour. From a formal point of view, many more bits of pathology than discussed in this review can be found in placentas and, with the advances in ultrasonography, might even be seen prior to birth. The extent of such a disturbance might ultimately affect fetal growth, which is amenable to prenatal detection offering the chances for an appropriate management. In contrast, dysmaturity is a great challenge as no predictive tests are as yet available.

Fetal varicella syndrome: disruption of neural development and persistent inflammation of non-neural tissues.

Abstract Primary varicella zoster virus (VZV) infection during pregnancy is rare. If it occurs between the 8th and 20th week of gestation, fetal varicella syndrome results in 1–2% of the fetuses. We report about a varicella infection that affected a pregnant mother in the 12th week of gestation. At 33 weeks, a premature girl was born with destruction of neurons in spinal cord, spinal ganglia and plexus myentericus, and secondary developmental disturbance including mummification of one arm and segmental intestinal atresia. The brain did not show any abnormalities. However, VZV DNA could be detected by PCR in tissues from the brain and spinal ganglia. Chronic necrotizing inflammation was found in the placenta, fetal membranes, and one ovary. These locations showed nuclear inclusions which by in-situ-hybridization were proven to be VZV derived. This case demonstrates that in the fetal age, ’neurotropism’ of VZV signifies severe destruction but not necessarily persistent inflammation of neural tissue. However, due to the inefficient fetal immune system, inflammation can go on for weeks, preferentially in non-neural tissues.

High‐resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power

The objective of this study was to determine for the first time the reliability and the diagnostic power of high‐resolution microarray testing in routine prenatal diagnostics.

Lethal multiple pterygium syndrome : Suggestion for a consistent pathological workup and review of reported cases

We report on 2 brothers with lethal multiple pterygium syndrome (LMPS) born to non-consanguineous parents as late spontaneous abortions. Both fetuses presented with massive nuchal edema, and facial anomalies including cleft palate and broad ribs. Apparently, several subgroups of LMPS exist. Differentiation is difficult, as there is no consistent agreement on a workup protocol for autopsies. We compared the findings in the literature on cases with LMPS, and we suggest a standardized workup as an initial step for more efficient differentiation between various subgroups.