Volume 36, Issue 4

Perinatal mortality and morbidity is markedly increased in intrauterine growth restricted (IUGR) fetuses. Prenatal identification of IUGR is the first step in clinical management. For that purpose a uniform definition and criteria are required. The etiology of IUGR is multifactorial and whenever possible it should be assessed. When the cause is of placental origin, it is possible to identify the affected fetuses. The major complication is chronic fetal hypoxemia. By monitoring the changes of fetal vital functions it is thus possible to improve both management and outcome. The timing of delivery is crucial but the optimal management scheme has not yet been identified. When IUGR is identified at very early gestational ages, serial assessments of the risk of continuing the in utero fetal life under adverse conditions versus the risks of the prematurity should be performed. Delivery of IUGR fetuses should take place in centers where appropriate neonatal assistance can be provided. Careful monitoring of the IUGR fetus during labor is crucial as the IUGR fetus can quickly decompensate once uterine contractions have started.

Preeclampsia (PE) is an important and a leading cause of both maternal morbidity and adverse perinatal outcomes. Despite progress in perinatal medicine for patients with an established diagnosis of PE, a therapeutic approach other than termination of pregnancy was unsuccessful. Women predisposed to PE begin pregnancy with a certain degree of endothelial dysfunction, a lesion that precedes shallow placentation. The proposed sequence of events comprises endothelial dysfunction, defective trophoblast invasion, and consequential impaired placental perfusion, immune maladaptation and inflammation. The possible link between these could be oxidative stress by excessive production of reactive oxygen species coupled with inadequate or overwhelmed antioxidant defense mechanisms. These defense mechanisms, involving antioxidant vitamins and enzyme systems, may restrain the extent of damage caused by oxidative stress. Markers of oxidative stress in women with established PE were confirmed. Accordingly, these findings support an expected beneficial effect of antioxidant therapy in the prevention of PE and other pregnancy-related disorders. Numerous studies have been carried out in order to investigate this possible and simple prophylactic and/or therapeutic approach in prevention of oxidative stress and eventual reduction of PE and its perinatal complications. In this review the role of vitamin antioxidants in prevention and treatment of PE is discussed. Despite the logic behind using antioxidant vitamins, the data, thus far, are at best conflicting.

Aims: Our objective was to elucidate the pathogenesis of twin discordance in four dizygotic pregnancies where only one of the twins had IUGR due to chronic villitis. Methods: We identified four cases of dizygotic twin placentas over a period of four years with evidence of chronic villitis. There was no clinical or pathologic evidence of TORCH, bacterial infection, preeclampsia or autoimmune disorders. Placentas were weighed, processed for histologic examination and stained with CD45RO (clone UCHL1) mouse monoclonal antibody, which identifies T-cells. Results: All placentas were dichorionic, with two being fused. Birth weight differences were 29%, 41%, 17% and 10%. Villitis was more marked in the placenta of the twin that weighed less and correlated with the degree of weight discordance. On examining the junction between the fused dichorionic placentas, the chorionic villi from the smaller twin contained numerous T-cells, whereas the villi associated with the less affected twin, showed little to no T-cells. Conclusion: We describe a series of dizygotic twin placentas where the more severe the chronic villitis, the more affected the placenta and fetus. Since the maternal environment was constant for each of these twins, differences in villitis severity appears to be attributable to differences in the ability of each placenta to induce a maternal immune response.

Aims: As the rate of cesarean sections has continuously increased over the last three decades, we sought to identify the factors related to elective cesarean section (ECS) and cesarean section during labor (LCS) in low risk pregnancies and to determine if they differ for the two types of cesarean. Methods: We conducted an observational study that included all maternity units in metropolitan France. Using the sample from the National Perinatal Survey 2003, we included 5393 women who met the criteria of a low risk pregnancy. The odds ratios (OR) corresponding to ECS and LCS were calculated for various characteristics for the women, fetus and maternity units, using a multinomial logistic regression model. For each factor, the adjusted OR corresponding to ECS and LCS were compared using the Wald's test. Results: The rates of ECS and LCS in our population were 2.9% and 4.3%, respectively. Maternal age ≥30 years, body mass index ≥25 kg/m 2 , primiparity and nationality from an African country were associated with an increased risk for both ECS and LCS. Those maternity units registering a low volume of deliveries (<1000/year) and those with a high rate of cesarean section during the previous year had an increased rate of LCS. Conclusion: Women with low risk pregnancies at term may present several factors that appear to create an “environment” favorable for cesarean section, leading to an increase in the likelihood of both ECS and LCS. Furthermore, several characteristics concerning maternity units are associated with an increased likelihood of LCS. Understanding the impact of various factors on the decision about the mode of delivery is essential for obstetrical teams concerned with controlling the progressive increase in the rate of cesarean sections.

Objectives : To investigate the obstetric antecedents for preterm delivery (PTD) in an Irish urban obstetric population, and to evaluate the incidence and outcome of such deliveries. Study design : A retrospective observational study of all preterm deliveries at the Rotunda Hospital, Dublin during the six-year period 1997–2002. The findings for early preterm deliveries (EPTD) (24+0–31+6 weeks' gestation), and late preterm deliveries (LPTD) (32+0–36+6 weeks' gestation) were analyzed separately. Results : There were 38,795 deliveries after 24 weeks' gestation or >500 g birth weight, of which 2839 (7.3%) were preterm. Of all preterm deliveries, 626 (22.1%) were EPTD and 2213 (77.9%) were LPTD, resulting in an EPTD rate of 1.6% and an LPTD rate of 5.7%. Spontaneous unexplained preterm delivery accounted for 1221 (43.0%) of preterm deliveries (PTD), and of these 213 (34%) cases were EPTD and 1008 (45.5%) LPTD. The other most frequently observed obstetric causative factors, in order of importance, were multiple gestation (676; 23.8% of PTD), hypertensive disorders of pregnancy (243; 8.6%), antepartum hemorrhage (194; 6.8%), stillbirth (105; 3.7%), intrauterine growth restriction (53; 1.9%) and preterm prelabor rupture of membranes±chorioamnionitis (32; 1.1%). There were 75 early neonatal deaths among infants born prematurely, plus 105 stillbirths, resulting in a perinatal mortality rate of 63 per 1000 for PTD (n=180), which on subsequent analysis was 158 per 1000 for EPTD (n=99) and 37 per 1000 for LPTD (n=81). Conclusions : These data outline the obstetric factors linked to preterm delivery within a recent Irish urban obstetric population. Spontaneous idiopathic preterm labor was the principle causative factor in 43% of all preterm deliveries, and represents the proportion of women for whom future therapeutic intervention may be of benefit.

Aim: To compare oxidative stress in patients with preeclampsia (PE) or intrauterine growth restriction (IUGR) vs. normal pregnancy (controls) during 48 h after delivery. Study design: Women with singleton pregnancies were recruited immediately after delivery (gestational age >26.0 weeks). Women with PE or IUGR were matched with healthy controls by age, BMI, gestational age and delivery mode. Venous blood samples and urine samples were tested for oxidative stress products 24 h and 48 h after delivery. Results: Plasma malondialdehyde (MDA) concentration 24 h after delivery was significantly higher in subjects with PE or IUGR (3.41±1.14 μmol/L, n=20) than in controls (2.91±0.82 μmol/L, n=38) (P=0.04). Urine iPF 2α -VI declined from 24 to 48 h after delivery significantly in controls (P=0.006) and not in subjects with PE or IUGR (P=0.71). Conclusion : Of the markers tested only MDA is indicating higher oxidative stress in women with PE/IUGR than in normal pregnancy and only at 24 h after delivery. No consistent pattern of change in the oxidative stress markers exists between 24–48 h after delivery.

Objective: The purpose of this study was to determine if: 1) insulin-like growth factor binding protein-1 (IGFBP-1) in amniotic fluid (AF) exhibited proteolytic cleavage in cases of intra-amniotic inflammation; and 2) if the matrix metalloproteinases (MMP-3, MMP-8, MMP-9) in AF are associated with the degradation of IGFBP-1 in AF. Methods : AF samples (n=20) were obtained from preterm gestations with and without intra-amniotic inflammation. The form of IGFBP-1 in AF was assessed by Western blot analysis and AF MMP-8 concentration was measured by ELISA. Densitometric analysis of Western blot was performed and the fragmented/intact IGFBP-1 ratio was calculated. Proteolysis of AF IGFBP-1 by MMPs was evaluated by incubating AF with exogenous human MMP-3, MMP-8 or MMP-9, and by incubating recombinant human IGFBP-1 in AF with and without inflammation. Results : 1) IGFBP-1 was present in AF without inflammation as an intact form; however, the fragmented form was dominant in AF with inflammation; 2) the ratio of fragmented/intact IGFBP-1 was significantly higher in AF with inflammation than in AF without inflammation; 3) a higher ratio of fragmented/intact IGFBP-1 was associated with a higher concentration of MMP-8; 4) in-vitro proteolysis experiments showed that AF IGFBP-1 was degraded by exogenous human MMP-3, MMP-8 and MMP-9; 5) recombinant human IGFBP-1 was fragmented in AF with inflammation, but not in AF without inflammation. Conclusion : The fragmented form of AF IGFBP-1 was significantly increased in AF with intra-amniotic inflammation, and MMPs produced in AF with intra-amniotic inflammation were associated with the proteolytic change of AF IGFBP-1.

Objective: To analyze the value of a single ultrasound biometry examination at the onset of the third trimester of pregnancy for the detection of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) at birth in a low risk population. The aim of this study was to develop a simple and useful method for the detection of growth deviations during pregnancy in primary care (midwife or general practitioner) practices. Setting: A Dutch primary care midwifery practice. Study design: In an earlier study, we developed parity and sex specific fetal growth charts of abdominal circumference (AC) and head circumference (HC) on the basis of ultrasound data of a low-risk midwifery population in the Netherlands. In the present study, we calculated sensitivity, specificity and predictive values at different cut-off points of AC and HC for the prediction of growth deviations at birth. Patients booked for perinatal care between 1 January 1993 and 31 December 2003 (n=3449) were used for the identification of cut-off points (derivation cohort) and those admitted between 1 January 2004 and 31 December 2005 (n=725) were used to evaluate the performance of these cut-offs in an independent population (validation cohort). For the determination of SGA and macrosomia at birth, we used the recently published Dutch birth weight percentiles. Results: Most promising cut-offs were AC ≤25 th percentile for the prediction of SGA (birth weight ≤10 th percentile) and AC ≥75 th percentile for the prediction of macrosomia (birth weight ≥90 th percentile). Within the validation cohort these cut-offs performed slightly better than in the derivation cohort. For the prediction of SGA, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 53% (95% CI 49–58%), 81% (95% CI 80–83%), 26% (95% CI 23–29%), and 93% (95% CI 93–94%), respectively. The false positive rate was 74%. For the prediction of macrosomia, the values of these parameters were 64% (95% CI 59–69%), 80% (95% CI 78–81%), 23% (95% CI 20–26%), and 96% (95% CI 95–97%), respectively. Here, false positive rate was 77%. No cut-offs were found that predicted extreme birth weight deviations (≤2.3 percentile; ≥97.7 percentile) sufficiently well. Conclusions: In a low risk population, we could predict future growth deviations with a higher sensitivity and in a significant earlier stage (at the onset of the third trimester of pregnancy) than with the use of conventional screening methods (i.e., palpation of the uterus only and fundus-symphysis measurement). Sonographic measurement of fetal abdominal circumference enables to detect more than half of cases of SGA at birth and more than two-thirds of cases of macrosomia with acceptable false-positive rates. We suggest that fetuses with biometry results below the 25 th percentile or above the 75 th percentile at the onset of the third trimester of pregnancy should be more intensively investigated in order to distinguish between pathology (e.g., IUGR or macrosomia) and physiology and to decide about the appropriate level of further perinatal care.

Aims: To compare the diagnostic accuracy of sonographic signs that may be looked for in fetuses with spina bifida. Methods: Forty-nine fetuses affected by spina bifida were enrolled, at a gestational age of 18–28 weeks. The following sonographic signs were looked for: “lemon” sign, small cerebellum, effaced cisterna magna, small posterior fossa, ventriculomegaly and direct visualization of a spinal defect. Results: The “lemon” sign was present in 53%, a small cerebellum in 96%, an effaced cisterna magna in 93%, a small posterior fossa in 96%. Ventriculomegaly was present in 40/49 (81%) cases and was severe in 20 fetuses and borderline in the remaining 20. The spinal defect was missed in one fetus presenting the cerebellar and posterior fossa signs. In two fetusus, the myelomeningocele was present without cranial signs of Chiari II malformation and in both cases the defect was covered by intact skin. Conclusions: Our results confirm the usefulness of evaluation of the posterior fossa in the diagnosis of spina bifida, particularly in cases of small spinal defects that may be missed at ultrasound. Conversely, myelomeningocele covered by intact skin was not associated with the cranial signs of Chiari II malformation.

Aims : To correlate data on umbilical cord arterial blood pH (pHa) levels obtained at delivery with subsequent Bayley Psychomotor Development (PDI) scores determined on the same cohort of children at age 18 months. Methods : At delivery, we obtained umbilical cord bloods for pHa levels along with other biological parameters. Following the birth cohort prospectively, at age 18 months we did a comprehensive, blinded neurodevelopmental examination to determine a PDI score for each child. Results : Over the broad range of umbilical cord arterial blood pH levels from 7.03 to 7.52, no statistically significant correlation (Pearson correlation coefficient, −0.016, P=0.88) was found between pHa at delivery and PDI scores at age 18 months. To study our finding in greater detail, we formed a subset of the data consisting only of lower pHa levels at delivery (defined as ≤7.20) and subsequent PDI scores. In this data subset, we again found that no significant relationship existed (Pearson correlation coefficient, +0.003, P=0.99). Conclusions : Our findings are consistent with the evolving hypothesis that adverse neurological outcomes in children often have etiologies other than intrapartum fetal acidemia.

Objectives : To assess risk factors for the growth and development of small-for-gestational age (SGA) infants whose birth weight was less than the 10 th percentile. Patients and methods : SGA infants who were admitted to the neonatal intensive care unit from 1995 to 1998 were enrolled in the study. Fifty-six SGA infants, having no chromosomal abnormalities, inherited diseases, TORCH infections, major anomaly and/or multiple birth, were divided into 34 asymmetrical and 22 symmetrical SGA infants by ≥ or <10 th percentile head circumference (HC) at birth. The physical growth including HC, and the developmental quotient (DQ) and intelligent quotient (IQ) scores were evaluated up to 6 years of age. Results : Symmetrical SGA infants had lower levels of weight, height and HC, but not of total DQ at 3 years or IQ scores at 6 years of age than asymmetrical SGA infants. The 21 SGA infants who had a HC less than the 10 th percentile at 1 year of age (non-catch-up group) showed lower total DQ (mean 96 vs. 105) and IQ (82 vs. 102) scores than 34 SGA infants who had not (catch-up group). Conclusions : These results suggested that psychomotor development of SGA infants depended on the HC at 1 year of age rather than that at birth.

Background: The incidence of early hypocalcemia in extremely low birthweight (ELBW) infants is unknown because the distribution of serum calcium values in this population is not defined. Objective: To determine the range of serum calcium values in ELBW infants during the first 48 h of life and the risks associated with low values. Design/methods: Retrospective analysis of all ELBW infants admitted on day 1 of life from April 2004 to October 2006. Demographic variables, therapy, serum calcium (Ca), pH, albumin, and blood ionized Ca were recorded. Results: There were 381 Ca levels obtained from 111 patients. Mean Ca was 6.90 mg/dL (1.73 mmol/L) (5 th –95 th percentile: 5.16–8.80). Ca levels rose after 24 h of life. Almost one quarter (23.1%) of the Ca levels were low by current standards. The majority of subjects (59.9%) had at least one hypocalcemic value. Conclusions: Serum Ca values are lower in ELBW infants and inconsequential. Thus, hypocalcemia should be re-defined for ELBW infants.

Objectives : To ascertain total body water in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns. Methods : SGA and AGA babies were matched by gestational age and studied from birth to term age. Criteria for exclusions were genetic syndromes, malformations, and congenital infections. Bioelectrical impedance was performed at two days of life (term infants), or at seven days of life and term age (preterm infants). Weight and length were measured by trained interviewers, and Z-score, weight/length ratio and Rohrer ponderal index was calculated. Results : Of the 54 infants evaluated, 28 were SGA (17 preterm) and 26 were AGA (15 preterm). Total body water was greater in SGA preterm babies at seven days of age (P=0.058) and at term age (P<0.0001). Weight/length ratio and Rohrer ponderal index increased towards term. Weight Z-score and anthropometric measures at term were significantly smaller in SGA babies. Being SGA and variation in Rohrer ponderal index influenced the variations in total body water. Conclusions : SGA babies had greater total body water, and both groups presented insufficient increase in body solid mass, stressing the importance of nutritional support during neonatal care.

Aims : To assess the presence of chorioamnionitis and intrauterine growth as prenatal risk factors for broncho pulmonary dysplasia (BPD) in appropriate-for-gestational-age (AGA) infants of <28 weeks' gestation. Methods : Gender, race, birth weight, gestational age, histology of the placenta, diagnosis of BPD at 36 weeks' gestation, postnatal dexamethasone treatment, and death were recorded in 150 preterm infants born at <28 weeks' gestation, and admitted between 1996 and 2001. Results: In 122 AGA infants (mean gestational age: 26.18 weeks, mean birth weight: 837 g), BPD was associated with gestational age-related birth weights below the 50 th centile. Intrauterine growth deceleration started between 25 and 26 weeks' gestation. Chorioamnionitis was not related to BPD. Conclusions: AGA infants of 26–28 weeks' gestation with birth weights below the median showed an increased risk of developing BPD.