Abstract: Objective To evaluate our experience with the diagnosis and treatment of Cesarean scar pregnancy. Methods During a 6-year period, 12 cases of Cesarean scar pregnancy were diagnosed using transvaginal color Doppler sonography and treated conservatively to preserve fertility. Incidence, gestational age, sonographic findings, β-human chorionic gonadotropin ( β-hCG) levels, flow profiles of transvaginal color Doppler ultrasound, and methods of treatment were recorded. Results The incidence of Cesarean scar pregnancy was 1:2216 and its rate was 6.1% in women with an ectopic pregnancy and at least one previous Cesarean section. Gestational age at diagnosis ranged from 5 + 0 to 12 + 4 weeks. The time interval from the last Cesarean section to the diagnosis of Cesarean scar pregnancy ranged from 6 months to 12 years. High-velocity and low-impedance subtrophoblastic flow (resistance index, 0.38) persisted until β-hCG declined to normal. Patients were treated as follows: transvaginal ultrasound-guided injection of methotrexate into the embryo or gestational sac (n = 3), transabdominal ultrasound-guided injection of methotrexate (n = 2), transabdominal ultrasound-guided injection of methotrexate followed by systemic methotrexate administration (n = 2), systemic methotrexate administration alone (n = 2), dilatation and curettage (n = 2), or local resection of the gestation mass (n = 1). Eleven of the 12 patients preserved their reproductive capacity; the remaining patient, treated by dilatation and curettage, underwent a hysterectomy because of profuse vaginal bleeding. The Cesarean scar mass regressed from 2 months to as long as 1 year after treatment. Uterine rupture occurred in one patient during the following pregnancy at 38 + 3 weeks' gestational age. Conclusion Ultrasound-guided methotrexate injection emerges as the treatment of choice to terminate Cesarean scar pregnancy. Surgical or invasive techniques, including dilatation and curettage are not recommended for Cesarean scar pregnancy due to high morbidity and poor prognosis. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.

Abstract: Consistent definitions to describe the length of gestation and age in neonates are needed to compare neurodevelopmental, medical, and growth outcomes. The purposes of this policy statement are to review conventional definitions of age during the perinatal period and to recommend use of standard terminology including gestational age, postmenstrual age, chronological age, corrected age, adjusted age, and estimated date of delivery.

Abstract: Until now oligonephropathy to indicate “too few nephrons” has been associated with intrauterine growth restriction and experimentally induced abnormalities of renal development. The purpose of this study was to determine whether there is evidence of abnormal postnatal glomerulogenesis in extremely low birth weight preterm infants. Renal autopsy tissue was studied by computer-assisted morphometry from 56 extremely premature infants (birth weight ≤ 1000 g) and 10 fullterm infants as controls. Preterm infants were divided into two groups (short survival < 40 days vs. long survival ≥40 days). Each group was subdivided into those with renal failure (RF) and those with normal renal function. Forty-two of 56 preterm infants (75%) were adequate for gestational age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly decreased in all preterm infants as compared to term controls and correlated significantly with gestational age (r = 0.87; P < 0.001). Active glomerulogenesis with “basophilic S-shaped bodies” was absent in longer surviving preterm and all term infants. RGC of preterm infants surviving ≥40 days with RF were significantly less than RGC of those with long survival and no RF (P < 0.001). Only this latter group demonstrated increased glomerular size as measured by mesangial tuft area and Bowman’s capsule area compared to all other groups (P < 0.001). The kidney continues to form postnatally in preterm neonates, but glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF. Compensatory mechanisms in longer surviving preterm infants include glomerular hypertrophy and mesangial proliferation that could lead to hyperfiltration.

Abstract: Objective: To evaluate the outcome for all infants born before 33 weeks gestation until discharge from hospital. Design: A prospective observational population based study. Setting: Nine regions of France in 1997. Patients: All births or late terminations of pregnancy for fetal or maternal reasons between 22 and 32 weeks gestation. Main outcome measure: Life status: stillbirth, live birth, death in delivery room, death in intensive care, decision to limit intensive care, survival to discharge. Results: A total of 722 late terminations, 772 stillbirths, and 2901 live births were recorded. The incidence of very preterm births was 1.3 per 100 live births and stillbirths. The survival rate for births between 22 and 32 weeks was 67% of all births (including stillbirths), 85% of live births, and 89% of infants admitted to neonatal intensive care units. Survival increased with gestational age: 31% of all infants born alive at 24 weeks survived to discharge, 78% at 28 weeks, and 97% at 32 weeks. Survival among live births was lower for small for gestational age infants, multiple births, and boys. Overall, 50% of deaths after birth followed decisions to withhold or withdraw intensive care: 66% of deaths in the delivery room, decreasing with increasing gestational age; 44% of deaths in the neonatal intensive care unit, with little variation with gestational age. Conclusion: Among very preterm babies, chances of survival varies greatly according to the length of gestation. At all gestational ages, a large proportion of deaths are associated with a decision to limit intensive care.

Abstract: Background. Unexplained antepartum stillbirth is a common cause of perinatal death, and identifying the fetus at risk is a challenge for obstetric practice. Intrauterine growth restriction (IUGR) is associated with a variety of adverse perinatal outcomes, but reports on its impact on unexplained stillbirths by population-based birthweight standards have been varying, including both unexplained and unexplored stillbirths. Aim. We have studied IUGR, assessed by individually adjusted fetal weight standards, in antepartum deaths that remained unexplained despite thorough postmortem investigations. Methods. Antenatal health cards from a complete population-based 10-year material of 76 validated sudden intrauterine unexplained deaths were compared to those of 582 randomly selected liveborn controls. Birthweight <10th percentile of the individualized standard adjusted for gestational age, maternal height, weight, parity, ethnicity, and fetal gender was defined as growth restriction. Results. 52% of unexplained s...

Abstract: Background— Untreated isolated fetal complete atrioventricular block (CAVB) has a significant mortality rate. A standardized treatment approach, including maternal dexamethasone at CAVB diagnosis and β-stimulation for fetal heart rates <55 bpm, has been used at our institutions since 1997. The study presents the impact of this approach. Methods and Results— Thirty-seven consecutive cases of fetal CAVB since 1990 were studied. Mean age at diagnosis was 25.6±5.2 gestational weeks. In 33 patients (92%), CAVB was associated with maternal anti-Ro/La autoantibodies. Patients were separated into those diagnosed between 1990 and 1996 (group 1; n=16) and those diagnosed between 1997 and 2003 (group 2; n=21). The 2 study groups were comparable in the clinical presentation at CAVB diagnosis but did differ in prenatal management (treated patients: group 1, 4/16; group 2, 18/21; P<0.0001). Overall, 22 fetuses were treated, 21 with dexamethasone and 9 with β-stimulation for a mean of 7.5±4.5 weeks. Live-birth and 1-yea...

Abstract: Objective To determine more precisely the incidence of fetal complications following maternal parvovirus B19 infection at various gestational ages. Methods An observational prospective study of 1018 pregnant women whose acute B19 infection was serologically confirmed in our laboratory. Results The observed rate of fetal death throughout pregnancy was 6.3% (64/1018) (95% confidence interval [CI]: 4.9, 8.0). The fetal death rate for those infected within the first 20 weeks of gestation (WG) was 64/579 (11.0%). Fetal death was only observed when maternal B19 infection occurred before the completed 20 WG. The observed stillbirth proportion was 0.6% (6/960). Three of six stillbirth cases presented with fetal hydrops. The overall risk of hydrops fetalis was 3.9% (40/1018) (95% CI: 2.8, 5.3). Three of 17 cases with non-severe hydrops and 13 of 23 cases with severe hydrops received intrauterine transfusion(s). The proportion of fetuses with severe hydrops that survived following fetal transfusions was 11/13 (84.6%). All of the non-transfused fetuses with severe hydrops died. Conclusion Our data demonstrate a relevant B19-associated risk of fetal death, which is largely confined to maternal B19 infection in the first 20 WG. Timely intrauterine transfusion of fetuses with severe hydrops fetalis reduces the risk of fetal death. Parvovirus B19-associated stillbirth without hydropic presentation is not a common finding. Copyright © 2004 John Wiley & Sons, Ltd.

Abstract: OBJECTIVE: The high rate of preterm births is an imposing public health issue in the United States. Past research has suggested that prenatal stress, anxiety, and elevated levels of maternal plasma corticotropin-releasing hormone (CRH) are associated with preterm delivery in humans and animals. Studies to date have not examined all three variables together; that is the objective of this paper. METHODS: Data from 282 pregnant women were analyzed to investigate the effect of maternal prenatal anxiety and CRH on the length of gestation. It was hypothesized that at both 18 to 20 weeks (Time 1) and 28 to 30 weeks gestation (Time 2), CRH and maternal prenatal anxiety would be negatively associated with gestational age at delivery. CRH was also expected to mediate the relationship between maternal prenatal anxiety and gestational age at delivery. RESULTS: Findings supported the mediation hypothesis at Time 2, indicating that women with high CRH levels and high maternal prenatal anxiety at 28 to 30 weeks gestation delivered earlier than women with lower CRH levels and maternal prenatal anxiety. Women who delivered preterm had significantly higher rates of CRH at both 18 to 20 weeks gestation and 28 to 30 weeks gestation (p <.001) compared with women who delivered term. CONCLUSIONS: These findings are the first to link both psychosocial and neuroendocrine factors to birth outcomes in a prospective design.

Abstract: ContextMaternal hypothyroidism and hyperthyroidism have deleterious effects on the outcome of pregnancy. While the effects of thyroid hormone (TH) deprivation on the fetus, independently from that on the mother, can be studied in infants with congenital hypothyroidism, this is not the case in those with fetal thyrotoxicosis.ObjectiveTo study the effects of TH excess on fetuses carried by mothers with resistance to TH (RTH) who are euthyroid despite high TH levels but who may carry normal fetuses that are exposed to high maternal hormone levels.Design, Setting, and ParticipantsRetrospective study of 167 members of an Azorean family with RTH. Affected individuals had the RTH phenotype (high serum concentration of free thyroxine and triiodothyronine without suppressed thyrotropin) confirmed by genotyping to identify the Arg243→Gln mutation in the TH receptor β gene.Main Outcome MeasuresPregnancy outcome of affected mothers vs that of unaffected mothers carrying fetuses conceived by affected fathers, as well as that of unaffected first-degree relatives and outcomes from the general island population. Comparison of birth weights and blood concentrations of thyrotropin (TSH) obtained during routine neonatal screening of infants born to these 3 groups.ResultsThirty-six couples with complete information belonged to 1 of 3 groups: affected mothers (n = 9), affected fathers (n = 9), and unaffected relatives (n = 18). Mean miscarriage rates were 22.9%, 2.0%, and 4.4%, respectively (χ2 = 8.66, P = .01). Affected mothers had an increased rate of miscarriage (z = 3.10, P = .002, by Wilcoxon rank-sum test). They had marginally higher than expected numbers of affected offspring, ie, 20 affected and 11 unaffected children (P = .07), while affected fathers had 15 affected and 12 unaffected children (P = .35). Unaffected infants born to affected mothers were significantly smaller than affected infants, having a mean SD score for gestational age of –1.79 (SD, 0.86) vs −0.06 (SD, 1.11) to –0.22 (SD, 0.70) for all other groups (P<.001). Only unaffected infants born to affected mothers had undetectable blood levels of TSH.ConclusionThere was a higher rate of miscarriage in mothers affected by RTH that may have involved predominantly unaffected fetuses. The lower birth weight and suppressed levels of TSH in unaffected infants born to affected mothers indicates that the high maternal TH levels produce fetal thyrotoxicosis. These data indicate a direct toxic effect of TH excess on the fetus.

Abstract: The fetal origins theory of adult disease suggests that term infants who are small for their gestational age have an increased susceptibility to chronic disease in adulthood as a consequence of physiologic adaptations to undernutrition during fetal life. Consistent evidence for an influence of women's dietary composition during pregnancy on growth of their babies is lacking, despite robust effects in animal experiments. We undertook a prospective observational study of 557 women aged 18-41 y, living in Adelaide, South Australia. Diet was assessed in early and late pregnancy using an FFQ. In early pregnancy, medians for energy intake, the proportion of energy derived from protein and from carbohydrate were 9.0 MJ, 17 and 48%, respectively. In late pregnancy the corresponding medians were 9.2 MJ, 16 and 49%. In early pregnancy, the percentage of energy derived from protein was positively associated with birth weight (P = 0.02) and placental weight (P = 0.07), independently of energy intake and weight gain during pregnancy, and after adjustment for potential confounders, including maternal age, parity, and smoking. Effects were stronger among women (n = 429) who had reliable data, based on prespecified criteria including the plausibility of dietary data when referenced against estimated energy expenditure. In addition, for this subgroup, the percentage of energy from carbohydrate in early and late pregnancy was negatively associated with ponderal index of the baby, and a specific effect of protein from dairy sources was identified. These data support the proposition that maternal dietary composition has an effect on fetal growth. Maternal diet in Western societies may therefore be important for the long-term health of the child.

Abstract: Objectives: Previous studies have implicated air pollution in increased mortality and morbidity, especially in the elderly population and children. More recently, associations with mortality in infants and with some reproductive outcomes have also been reported. The aim of this study is to explore the association between exposure to outdoor air pollution during pregnancy and birth weight. Design: Cross sectional study using data on all singleton full term live births during a one year period. For each individual birth, information on gestational age, type of delivery, birth weight, sex, maternal education, maternal age, place of residence, and parity was available. Daily mean levels of PM 10 , sulphur dioxide, nitrogen dioxide, carbon monoxide, and ozone were also gathered. The association between birth weight and air pollution was assessed in regression models with exposure averaged over each trimester of pregnancy. Setting: Sao Paulo city, Brazil. Results: Birth weight was shown to be associated with length of gestation, maternal age and instruction, infant gender, number of antenatal care visits, parity, and type of delivery. On adjusting for these variables negative effects of exposure to PM 10 and carbon monoxide during the first trimester were observed. This effect seemed to be more robust for carbon monoxide. For a 1 ppm increase in mean exposure to carbon monoxide during the first trimester a reduction of 23 g in birth weight was estimated. Conclusions: The results are consistent in revealing that exposure to air pollution during pregnancy may interfere with weight gain in the fetus. Given the poorer outlook for low birthweight babies on a number of health outcomes, this finding is important from the public health perspective.

Abstract: Hypertensive disorders in pregnancy are leading causes of maternal, fetal and neonatal morbidity and mortality worldwide. However, studies attempting to quantify the effect of hypertension on adverse perinatal outcomes have been mostly conducted in tertiary centres. This population-based study explored the frequency of hypertensive disorders in pregnancy and the associated increase in small for gestational age (SGA) and stillbirth. We used information on all pregnant women and births, in the Canadian province of Nova Scotia, between 1988 and 2000. Pregnancies were excluded if delivery occurred < 20 weeks, if birthweight was < 500 grams, if there was a high-order multiple pregnancy (greater than twin gestation), or a major fetal anomaly. The study population included 135,466 pregnancies. Of these, 7.7% had mild pregnancy-induced hypertension (PIH), 1.3% had severe PIH, 0.2% had HELLP (hemolysis, elevated liver enzymes, low platelets), 0.02% had eclampsia, 0.6% had chronic hypertension, and 0.4% had chronic hypertension with superimposed PIH. Women with any hypertension in pregnancy were 1.6 (95% CI 1.5–1.6) times more likely to have a live birth with SGA and 1.4 (95% CI 1.1–1.8) times more likely to have a stillbirth as compared with normotensive women. Adjusted analyses showed that women with gestational hypertension without proteinuria (mild PIH) and with proteinuria (severe PIH, HELLP, or eclampsia) were more likely to have infants with SGA (RR 1.5, 95% CI 1.4–1.6 and RR 3.2, 95% CI 2.8–3.6, respectively). Women with pre-existing hypertension were also more likely to give birth to an infant with SGA (RR 2.5, 95% CI 2.2–3.0) or to have a stillbirth (RR 3.2, 95% CI 1.9–5.4). This large, population-based study confirms and quantifies the magnitude of the excess risk of small for gestational age and stillbirth among births to women with hypertensive disease in pregnancy.

Abstract: Objective To study the effect of using smokeless tobacco during pregnancy on babies9 birth weight and gestational age at birth. Design Population based, prospective cohort study using a house to house approach. Setting Eight primary health post areas in the city of Mumbai (Bombay), India. Participants 1217 women who were three to seven months pregnant and planning to deliver in the study area. 1167 women (96%) were followed up. Main outcome measures Birth weight and gestational age in singleton births. Results Smokeless tobacco use was associated with an average reduction of 105 g in birth weight (95% confidence interval 30 g to 181 g) and a reduction in gestational age of 6.2 (3.0 to 9.4) days. The odds ratio for low birth weight was 1.6 (1.1 to 2.4), adjusted by logistic regression for maternal age, education, socioeconomic status, weight, anaemia, antenatal care, and gestational age. The adjusted odds ratio for preterm delivery (< 37 weeks) was 1.4 (1.0 to 2.1); for delivery before 32 weeks it was 4.9 (2.1 to 11.8) and before 28 weeks it was 8.0 (2.6 to 27.2). Conclusions Consumption of smokeless tobacco during pregnancy decreases gestational age at birth and birth weight independent of gestational age. It should receive specific attention as a part of routine prenatal care.

Abstract: This study was performed to clarify alterations in lamotrigine (LTG) clearance during pregnancy and childbirth. Fourteen women on LTG monotherapy had LTG concentration samples obtained before conception and monthly. LTG apparent clearance, weight-adjusted relative clearance, and percentages of baseline clearance significantly differed between preconception baseline and each trimester and between trimesters. LTG clearance progressively increased until 32 weeks' gestational age, reaching a peak of >330% of baseline, and then began to decline.

Abstract: OBJECTIVE: To examine the impact of maternal obesity on the rate of suboptimal ultrasound visualization (SUV) of fetal anatomy and determine the optimal timing of prenatal ultrasound examination for the obese gravida. METHODS: A computerized ultrasound database was used to identify ultrasound examinations for singleton gestations performed between 140/7 and 236/7 weeks at a tertiary care, university-based hospital. Patients were divided into four groups and categorized based on body mass index (BMI): nonobese (BMI <30 kg/m2), class I obesity (30≤BMI<35 kg/m2), class II obesity (35≤BMI<40 kg/m2), and extreme obesity (BMI ≥40 kg/m2). The rates of SUV for fetal cardiac and craniospinal structures were calculated for each group and compared. RESULTS: A total of 11 019 pregnancies were studied, of which 38.6% of the patients were obese. Overall, the rate of SUV of the fetal structures was higher for obese compared to nonobese women for both cardiac (37.3 [1723/4200] vs 18.7% [1275/6819]; P<0.0001) and craniospinal structures (42.8 [1798/4200] vs 29.5% [2012/6819]; P<0.0001). Increased severity of maternal obesity was associated with SUV rate for both the cardiac (nonobese 18.7% [1275/6819], class I 29.6% [599/2022], class II 39.0% [472/1123], and extreme obesity 49.3% [580/1055]; P<0.0001) and for the craniospinal structures: (nonobese 29.5% [2012/6819], class I 36.8% [744/2022], class II 43.3% [486/1123], and extreme obesity 53.4% [563/1055]; P<0.0001). With increasing gestational age at examination, the rate of SUV decreased for both obese and nonobese women. However, for obese women there was minimal improvement in visualization after 18–20 weeks. Even after adjustment for gestational age and the type of ultrasound machine, obese women (class I, class II, and extreme obesity) were still associated with increased odds for SUV of the fetal cardiac and craniospinal structures compared to nonobese women. CONCLUSION: Maternal obesity increases the rate of SUV for the fetal cardiac structures by 49.8% and for the craniospinal structures by 31%. The optimal gestational age for visualization of fetal cardiac and craniospinal anatomy in obese patients may be after 18–20 weeks.

Abstract: Objective. Long-term outcome, including school-age function, has been infrequently reported in infants born at ages as young as 23–26 weeks’ gestation. The objective of this study is to report outcome on a large cohort of these infants to understand better the risks and factors that affect survival and long-term prognosis. Methods. Records from 1036 infants who were born between January 1, 1986, and December 31, 2000, were analyzed retrospectively by logistic regression to correlate multiple factors with both survival and long-term outcome. A total of 675 surviving infants were analyzed at a mean age of 47.5 months for developmental outcome. A subset of 147 surviving infants who were born before 1991 were followed through school-age years using the University of Vermont Achenbach Child Behavioral Checklist and Teachers Report Form. Longitudinal follow-up was performed comparing 1-year outcome with school-age performance. Results. Gestational age and recent year of birth correlated highly with survival. Maternal nonwhite race, female sex, inborn status, surfactant therapy, single gestation, and secondary sepsis also correlated positively with survival. Normal cranial ultrasound results, absence of chronic lung disease, female sex, cesarean delivery, and increased birth weight correlated favorably with long-term outcome. Infants who were born at 23 weeks were more likely to have severe impairments compared with those who were born at 24–26 weeks. Early follow-up identified most subsequent physical impairments but correlated poorly with school-age function. Conclusions. Survival continues to improve for infants who are born at extremely early gestational ages, but long-term developmental concerns continue to be prevalent. Early outcomes do not reliably predict school-age performance. Strategies that reduce severe intraventricular hemorrhage and chronic lung disease will likely yield the best chances to improve long-term outlook.

Abstract: In developed countries, cerebral palsy (CP) remains the most common form of severe physical disability in children. Approximately 25 years ago, the rate of CP was found to be substantially increased in low-birth-weight children, but the cause of CP still is poorly understood. The authors report a survey of 10 European registers totaling 4503 singleton children with CP who were born in the years 1976 through 1990. The goal was to learn whether altered intrauterine growth is a pathologic factor in the origin of CP. CP was defined as a group of disorders that involve disordered movement, posture, or both as well as motor dysfunction. It is a permanent condition that can change but is not progressive. Using conventional fetal growth standards, infants born at 32 to 42 weeks gestation whose birth weight for gestational age was below the 10th percentile were 4 to 6 times more likely to have CP than were reference children with birth weights between the 25th and 75th percentiles. The increase in risk was considerably less (1.6- to 3.1-fold)-but still significant-in children whose birth weights were above the 97th percentile. The risk of CP was lowest in children whose birth weights were approximately 1 standard deviation above average. Similar findings were obtained for infants having unilateral or bilateral spasticity, and also for those who were dyskinetic or ataxic. The relationship between birth weight and risk of CP, if any, was less clear in children who were born before 32 weeks gestation. As is the case for perinatal death, the risk of CP is lowest in infants who at birth are above average weight for gestational age. However, the risk of CP increases not only when birth weight is well below normal, but also when it is well above normal. Possibly an abnormal growth pattern causes CP, or vice versa, or there could be some factor that is linked independently to both growth and the risk of CP. Conceivably, brain damage or impaired development in utero triggers an abnormal growth pattern through an endocrine pathway or some other mechanism. An alternative explanation is that abnormal growth renders the fetus more vulnerable physiologically, and that the brain is exposed to irreparable darnage during or after delivery.

Abstract: Background and Objective:The aim of this study was to identify those risk factors most likely to lead to the development of RSV-related respiratory Infection and subsequent hospital admission among premature infants born at 33–35 WGA (FLIP study)Methods:This was a prospective case-control study. Cas