Volume 35, Issue 1

Treatment of cervical intraepithelial neoplasia (CIN) greatly reduces the risk of cervical cancer. Treatment involves ablation or excision of the transformation zone of the cervix, most commonly using an electrosurgical excision technique known as LLETZ. However, the peak incidence of CIN occurs in young women, so if excision of a portion of the cervix has an adverse effect on pregnancy outcome, this might have a significant impact. This review discusses the methodology and findings of the published literature on the association between cervical treatment and preterm birth, and the clinical implications of these findings.

Aim: The purpose of this paper is to review and analyze the published literature on the use of three-dimensional (3DUS) and four-dimensional (4DUS) ultrasound in perinatal medicine. Methods: We systematically searched Medline through PubMED (January 2000–January 2006), including EMBASE/Excerpta Medica database as well as the Cochrane Database of Systematic Reviews. The search terms used to identify clinical application of 3DUS and 4DUS studies in perinatal medicine were technical development, special features, and recommendation for fetal imaging, research on 3DUS or 4DUS, and the usage of invasive 3DUS or 4DUS procedures. The reference bibliographies of relevant books were also manually searched for supplementary citations. Inclusion criteria were as follows: (1) studies related to the use of 3DUS or 4DUS in perinatal medicine; (2) full text were available in English; (3) publication format of original scientific articles, case reports, editorials or literature reviews and chapters in the books. Results: Five hundred and seventy-five articles were identified, and among those, 438 were relevant to this review. Conclusions: 3DUS and 4DUS provided additional information for the diagnosis of facial anomalies, evaluation of neural tube defects, and skeletal malformations. Additional research is needed to determine the clinical utility of 3DUS and 4DUS for the diagnosis of congenital heart disease, central nervous system (CNS) anomalies and detection of fetal neurodevelopmental impairment assessed by abnormal behavior in high-risk fetuses.

Aims: Cigarette smoking during pregnancy is associated with a lower risk of preeclampsia, whereas obesity increases the risk of preeclampsia. We sought to assess the combined effect of smoking and obesity on the risk of preeclampsia. Methods: We conducted a population-based cohort study of 129,674 women who delivered singleton infants during 2000–2001. Data for cigarette use, pre-pregnancy body mass index (BMI), preeclampsia, and potential confounders were obtained from birth certificate files. Mantel-Haenszel stratified analysis and logistic regression were used to analyze the data. Results: The preeclampsia risk was 3.1, 4.5, 7.6 and 8.8% for normal weight (BMI 18.5–24.9), overweight (25.0–29.9), obese (30.0–39.9) and morbidly obese (≥40.0 kg/m 2 ) women, respectively, who smoked cigarettes while pregnant. The preeclampsia risk was 3.9, 6.2, 9.0 and 12.3% for the same groups of women, respectively, who did not smoke during their pregnancy. Compared to non-smokers, the relative risk of preeclampsia for women who smoked cigarettes was 0.78 (95% confidence interval 0.73–0.83) before and after adjusting for pre-pregnancy BMI and other factors associated with preeclampsia. Conclusion: The risk of preeclampsia is lower for women who smoke cigarettes while pregnant regardless of their pre-pregnancy BMI.

Objective: This study evaluates the impact of an average change in body mass index (BMI) during the first 16–25 weeks on outcomes of triplet pregnancies. Study design : In this retrospective observational study we evaluated a cohort of triplets born to 1235 nulliparas and 705 multiparas. The difference between the pregravid body mass index (BMI) and that obtained upon admission at 16–25 weeks' gestation was averaged to obtain the weekly change in BMI, defined as slow, typical, or fast by values <1SD, ±1SD, and >1SD from the mean average weekly change in BMI. We compared gestational age and birth weight parameters in these three subgroups and by parity. Results: The average weekly BMI-adjusted weight gain was 0.18±0.08 and 0.17±0.08 kg/m 2 /week for nulliparas and multiparas, respectively. In both parity groups, differences were noted between slow and typical and between slow and fast, but not between typical and fast weight gain. Nulliparas with slow weight gain had a significantly higher incidence of infants weighing <1000 g (OR 2.0–2.5), 1000–1500 g (OR 1.4 compared with fast weight gain), and included 60–100% more sets with at least 1 SGA infant. In multiparas, there was no effect on gestational age, but otherwise, a similar trend for birth weight parameters was found. Conclusion: Slow weekly change in BMI (<1 SD from the mean) at 16–25 weeks is associated with decreased birth weight but there was no advantage for fast over a typical weigh gain.

Aims: Both acute placental inflammation and positive mid-gestational cervico-vaginal fetal fibronectin assays have been independently correlated with preterm delivery. We conducted this study to examine the relationship between positive mid-gestational fetal fibronectin (fFN) assays and histological evidence of acute placental inflammation at delivery among women presenting with symptomatic preterm labor. Methods: This retrospective chart review included women who underwent cervico-vaginal fFN testing for preterm contractions between 24–34 weeks gestation and also had placental histological analysis after delivery. Women with a multiple gestation, cerclage, preterm premature rupture of membranes, intercourse or vaginal bleeding within 24 h before the assay were excluded. The primary outcome was histological evidence of acute placental inflammation defined as acute chorioamnionitis, acute deciduitis, funisitis, or microabscess formation. Results: Of 82 women who met all study inclusion criteria, 45% were fFN positive. Women with positive assays were no more likely to have histological evidence of acute inflammation noted at birth than women with negative assays (45% vs. 26%, P=0.07). The assay had a sensitivity of 58.6%, specificity of 62.3%, positive predictive value of 46.0%, and negative predictive value of 73.3% for predicting acute inflammation at delivery. Conclusions: No association exists between positive fetal fibronectin assays and acute histologic placental inflammation at birth.

Aims: An association between paternal age and type 1 diabetes (IDDM) among their offspring was recently reported as well as transgenerational responses in humans. This paper aims to assess the association of markers for prenatal exposures with IDDM. Methods: We analysed data from two birth cohorts in Great Britain on 5214 cohort members from the National Child Development Study (NCDS) and 6068 members of the 1970 British Birth Cohort Study (BCS70) with full information on IDDM and explanatory variables using multivariate logistic regression. Results: IDDM prevalence was 0.7% (95% CI 0.5–1.0%; n=38) in the NCDS and 0.4% (95% CI 0.3–0.6%; n=27) in the BCS70 cohort. Paternal age was not associated with IDDM possibly due to lack of sample power. Unexpectedly, a lowered prevalence of IDDM was observed among offspring of smoking fathers in both cohorts, with a combined odds ratio of 0.44 (95% CI 0.25–0.75). This association could not be explained by maternal smoking prior to, during or after pregnancy, number of siblings, parental social class, maternal and paternal age, or cohort. Maternal smoking in pregnancy did not alter the IDDM prevalence among offspring. Conclusions: This unexpected finding may be explained by germ-line mutations or other mechanisms associated with paternal smoking. This phenomenon should be investigated and these results should not be used as a justification for smoking. Paternal exposures may be important in determining IDDM risk.

Aim: To assess the sonographic cervical characteristics between nulliparous and multiparous women. Subject and methods: Transvaginal three-dimensional ultrasound and power Doppler using the virtual organ computer-aided analysis (VOCAL) program were performed on 71 nulliparas and 59 multiparas at a mean gestational age of 25.3±7.9 weeks. We compared the cervical volume and power Doppler vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) between nulliparas and multiparas. Results: The mean cervical volume and mean VI, VFI, FI measurements were not significantly different between multiparas and nulliparas. Conclusion: Our observations suggest that the morphological changes in the cervix of parous women are merely configurational without a change in cervical mass and vascularization. These configurational changes might result from the inevitable cervical streching during labor and represent a healing process that does not involve a subsequent change in mass or vascularity.

Objectives: To determine fetal growth in low risk pregnancies at the beginning of the third trimester and to assess the relative importance of fetal gender and maternal parity. Setting: Dutch primary care midwifery practice. Study design: Retrospective cohort study on 3641 singleton pregnancies seen at a primary care midwifery center in the Netherlands. Parameters used for analysis were fetal abdominal circumference (AC), fetal head circumference (HC), gestational age, fetal gender and maternal parity. Regression analysis was applied to describe variation in AC and HC with gestational age. Means and standard deviations in the present population were compared with commonly used reference charts. Multiple regression analysis was applied to examine whether gender and parity should be taken into account. Results: The fetal AC and HC increased significantly between the 27 th and the 33 rd week of pregnancy (AC r 2 =0.3652, P<0.0001; HC r 2 =0.3301, P<0.0001). Compared to some curves, our means and standard deviations were significantly smaller (at 30+0 weeks AC mean=258±13 mm; HC mean=281±14 mm), but corresponded well with other curves. Fetal gender was a significant determinant for both AC (P<0.0001) and HC (P<0.0001). Parity contributed significantly to AC only but the difference was small (β=0.00464). Conclusion: At the begining of the third trimester, fetal size is associated with fetal gender and, to a lesser extent, with parity. Some fetal growth charts (e.g., Chitty et al.) are more suitable for the low-risk population in the Netherlands than others.

Objective : The aim of our study is to evaluate the clinical importance of near term weight discordance in twin pregnancies with both appropriate or with one small for gestational age newborn (AGA and SGA, respectively). Methods : We retrospectively studied 230 twin pregnancies that ended at ≥34 weeks′ gestation. Discordance was defined as an intertwin birth weight difference ≥20% calculated from the heavier newborn. The following data were compared between discordant and concordant pairs: maternal age, parity, mode of conception, placentation, hypertensive disorders of pregnancy, gestational age at birth, route of delivery, reason for termination of pregnancy, Apgar scores, birth weights, admission to neonatal intensive care unit, significant morbidity, malformations found at birth, and perinatal mortality. The discordant pairs were subdivided into two groups: (1) Both twins were AGA; (2) One of the twins was SGA. The two groups were compared to each other, and to the control group of concordant pairs. Results : One hundred and seventy-six twin pairs were concordant (control group) and 54 were discordant. The comparison between the concordant and the discordant groups did not show statistically significant differences in any of the examined parameters. However, the discordant group had a greater incidence of neonatal morbidity. When the discordant subgroups (AGA, n=24 vs. SGA n=30) were compared to the concordant group, these differences persist, particularly in the SGA group. Conclusion : In near term twin pregnancies, birth weight discordance does not seem to predict adverse perinatal outcome except when one of the newborns is SGA.

Aims: Intracerebellar hemorrhage is a rarely confirmed diagnosis in preterm infants in comparison to peri-/intraventricular hemorrhage. This study evaluates the incidence of intracerebellar hemorrhage and neurological outcome in preterm infants. Methods: 260 infants with gestational age of 22–32 weeks were studied prospectively by cranial ultrasound. Neurodevelopmental outcome was examined in the first three years of life. Results: 15 infants had intracranial hemorrhage grade II-IV (10 intraventricular, 6 intracerebellar hemorrhage). Neurodevelopmental follow-up showed that one infant with intracerebellar hemorrhage is severely handicapped, two have moderate and two mild impairments and one has no sequelae. Conclusion: Cerebellar hemorrhage is not rare if ultrasound examination is specifically focused on cerebellar lesions.

Objective: To compare O 2 consumption, CO 2 production, respiratory quotient and resting metabolic rate in premature neonates measured for 5 and 10 min steady-state periods and 15 and 20 min non-steady-state periods versus a 2-h measurement period. Methods: A prospective study with neonates evaluated by indirect calorimetry. The measurements from the 5, 10, 15, and 20 min periods were taken based on the printout data from the IC monitor at an interval of 1 h before the beginning feeding and were contained in the 2-h measurement. The 5- and 10-min measurements followed the steady-state criterion. Results: We evaluated 35 premature neonates appropriate for gestational age (born at 28–34 weeks' gestation). Mean age was 20 days ±9 (median 14 days) and mean weight was 1530±270 g (median 1510 g). There was no statistically significant difference between mean VO 2 , VCO 2 , respiratory quotient and energy expenditure at 5, 10, 15, and 20 min and 2 h. Conclusions: The 5 and 10 min steady-state measurements or a measurement of more than 15 min without reaching steady state produce results similar to those of 2 h measurements.

Objective: An association between maternal HELLP syndrome and fetal long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been proposed. LCHAD catalyzes the third step in the β-oxidation of fatty acids in mitochondria. Whereas about 75% of LCHAD-deficient patients carry a G-to-C mutation at nucleotide position 1528 (Glu474Gln, E474Q) on both chromosomes, compound heterozygosity for E474Q on one chromosome and a second different LCHAD mutation on the other can be observed in up to 25% of LCHAD-deficiency cases; only very few patients carry two mutations different from E474Q. Genetic analysis of the mother alone is insufficient in case of compound heterozygosity. Since information on the fetal carrier status of the E474Q mutation in maternal HELLP syndrome is rare, we investigated the frequency of the E474Q mutation in families where the mother had HELLP syndrome. Methods: The occurrence of the E474Q mutation was analyzed by PCR and RFLP in 103 mothers with HELLP syndrome, in 82 children of affected pregnancies and in 21 fathers in families where fetal DNA was not available. In addition, 103 control women with only uncomplicated pregnancies were investigated. Results: The mutation E474Q was not detected in the study population. Conclusion: Neither maternal nor fetal heterozygosity for the E474Q mutation is a relevant factor of HELLP syndrome.

Aim: To analyze the management of newborns after major surgery receiving morphine subcutaneously and to identify possible side effects. Methods: Morphine was administered via a subcutaneous catheter (Insuflon ® ) in 20 newborns after major surgery. Side effects like hypotension, pain during morphine administration and local infection were noted. Morphine dose was adjusted according to the hospital guidelines with the Neonatal Infant Pain Score (NIPS) and the Finnegan withdrawal score. Results: Surgery was performed at the median age of 38 5/7 weeks (range: 32 1/7–49 5/7 weeks). Before starting subcutaneous morphine administration, patients received intravenous morphine for a median of two weeks (range six days to seven weeks). All patients showed good pain relief with no severe side effects. Three patients reacted with crying to the first dose of subcutaneous morphine. No other side effects occurred. Conclusion: Subcutaneous application of morphine with the Insuflon ® catheter is an alternative to intravenous treatment of postoperative pain in neonates. In this small group pain relief was good and side effects were harmless.