Abstract: Objective To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery. Design Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health. Setting 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided data Participants 106 546 deliveries reported during the three month study period, with data available for 97 095 (91% coverage). Main outcome measures Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics. Results Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective. Conclusions Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations.

Abstract: Depending on the definitions used, up to 10% of all live-born neonates are small for gestational age (SGA). Although the vast majority of these children show catch-up growth by 2 yr of age, one in 10 does not. It is increasingly recognized that those who are born SGA are at risk of developing metabolic disease later in life. Reduced fetal growth has been shown to be associated with an increased risk of insulin resistance, obesity, cardiovascular disease, and type 2 diabetes mellitus. The majority of pathology is seen in adults who show spontaneous catch-up growth as children. There is evidence to suggest that some of the metabolic consequences of intrauterine growth retardation in children born SGA can be mitigated by ensuring early appropriate catch-up growth, while avoiding excessive weight gain. Implicitly, this argument questions current infant formula feeding practices. The risk is less clear for individuals who do not show catch-up growth and who are treated with GH for short stature. Recent data, however, suggest that long-term treatment with GH does not increase the risk of type 2 diabetes mellitus and the metabolic syndrome in young adults born SGA.

Abstract: Objectives This report presents 2003 fetal and perinatal mortality data by a variety of characteristics, including maternal age, marital status, race, Hispanic origin, and state of residence; and by infant birthweight, gestational age, plurality, and sex. Trends in fetal and perinatal mortality are also examined. Methods Descriptive tabulations of data are presented and interpreted. Results The U.S. fetal mortality rate in 2003 was 6.23 fetal deaths of 20 weeks of gestation or more per 1,000 live births and fetal deaths. Fetal and perinatal mortality rates have declined slowly but steadily from 1990 to 2003. Fetal mortality rates for 28 weeks of gestation or more have declined substantially, whereas those for 20-27 weeks of gestation have not declined. Fetal mortality rates are higher for a number of groups, including non-Hispanic black women, teenagers, women aged 35 years and over, unmarried women, and multiple deliveries. Over one-half (51 percent) of fetal deaths of 20 weeks of gestation or more occurred between 20 and 27 weeks of gestation.

Abstract: Familial correlations in birth weight and gestational age have been explained by fetal and maternal genetic factors, mainly in studies on offspring of twins. The aim of the present intergenerational study was to estimate and compare fetal and maternal genetic effects and shared sibling environmental effects on birth weight and gestational age and also on crown-heel length and head circumference. The authors used path analysis and maximum likelihood principles to estimate these effects and, at the same time, to adjust for covariates. Parent-offspring data were obtained from the Medical Birth Registry of Norway from 1967 to 2004. For the analysis of birth weight and crown-heel length, 101,748 families were included; for gestational age, 91,617 families; and for head circumference, 77,044 families. Assuming no cultural transmission and random mating, the authors found that fetal genetic factors explained 31% of the normal variation in birth weight and birth length, 27% of the variation in head circumference, and 11% of the variation in gestational age. Maternal genetic factors explained 22% of the variation in birth weight, 19% of the variation in birth length and head circumference, and 14% of the variation in gestational age. Relative to the proportion of explained variation, fetal genes were most important for birth length and head circumference.

Abstract: BACKGROUND. There is a paucity of information on the maintenance of body temperature at birth for low birth weight infants. OBJECTIVES. We examined the distribution of temperatures in low birth weight infants on admission to the NICUs in the Neonatal Research Network centers and determined whether admission temperature was associated with antepartum and birth variables and selected morbidities and mortality. METHODS. Infants without major congenital anomalies born during 2002 and 2003 with birth weights of 401 to 1499 g who were admitted directly from the delivery room to the NICU were included. Bivariate associations between antepartum/birth variables and admission temperature and selected morbidities/mortality and admission temperature were examined, followed by multivariable linear or logistic regressions to detect independent associations. RESULTS. There were 5277 study infants and the mean (±SD) birth weight and gestational age were 1036 ± 286 g and 28 ± 3 weeks, respectively. The distribution of admission temperatures was 14.3% at CONCLUSIONS. Preventing decreases in temperature at birth among low birth weight infants remains a challenge. Associations with intubation and center of birth suggest that assessment of temperature control for infants intubated in the delivery room may be beneficial. Whether the admission temperature is part of the casual path or a marker of mortality needs additional study.

Abstract: OBJECTIVE —The purpose of this study was to examine rates and factors associated with recurrence of gestational diabetes mellitus (GDM) among women with a history of GDM. RESEARCH DESIGN AND METHODS —We conducted a systematic literature review of articles published between January 1965 and November 2006, in which recurrence rates of GDM among women with a history of GDM were reported. Factors abstracted included recurrence rates, time elapsed between pregnancies, race/ethnicity, diagnostic criteria, and, when available, maternal age, parity, weight or BMI at the initial and subsequent pregnancy, weight gain at the initial or subsequent pregnancy and between pregnancies, insulin use, gestational age at diagnosis, glucose tolerance test levels, baby birth weight and presence of macrosomia, and breast-feeding. RESULTS —Of 45 articles identified, 13 studies were eligible for inclusion. After the index pregnancy, recurrence rates varied between 30 and 84%. Lower rates were found in non-Hispanic white (NHW) populations (30–37%), and higher rates were found in minority populations (52–69%). Exceptions to observed racial/ethnic variations in recurrence were found in cohorts that were composed of a significant proportion of both NHW and minority women or that included women who had subsequent pregnancies within 1 year. No other risk factors were consistently associated with recurrence of GDM across studies. The rates of future preexisting diabetes in pregnancy, socioeconomic status, postpartum diabetes screening rates after the index pregnancy, and the average length of time between pregnancies were generally not reported. CONCLUSIONS —Recurrence of GDM was common and may vary most significantly by NHW versus minority race/ethnicity.

Abstract: Background Maternal thyroid dysfunction has been associated with a variety of adverse pregnancy outcomes. Laboratory measurement of thyroid function plays an important role in the assessment of maternal thyroid health. However, occult thyroid disease and physiologic changes associated with pregnancy can complicate interpretation of maternal thyroid function tests (TFTs). Objective and methods To 1) establish the prevalence of laboratory evidence for autoimmune thyroid disease (AITD) in pregnant women; 2) establish gestational age-specific reference intervals for TFTs in women without AITD; and 3) examine the influence of reference intervals on the interpretation of TFT in pregnant women. Serum samples were collected from 2272 pregnant women, and TFT performed. Gestational age-specific reference intervals were determined in women without AITD, and then compared with the non-pregnant assay-specific reference intervals for interpretation of testing results. Results Thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin antibodies (Tg-Ab) were positive in 10.4 and 15.7% of women respectively. TPO-Ab level was related to maternal age, but TPO-Ab status, Tg-Ab status, and Tg-Ab level were not. Women with TSH > 3.0 mIU/l were significantly more likely to be TPO-Ab positive. Gestational age-specific reference intervals for TFT were significantly different from non-pregnant normal reference intervals. Interpretation of TFT in pregnant women using non-pregnant reference intervals could potentially result in misclassification of a significant percentage of results (range: 5.6-18.3%). Conclusion Laboratory evidence for thyroid dysfunction was common in this population of pregnant women. Accurate classification of TFT in pregnant women requires the use of gestational age-specific reference intervals.

Abstract: Objective Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth. Methods This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at ≤ 32 weeks of gestation. The trial was analyzed using an intent-to-treat strategy. Results Baseline characteristics were similar in the two treatment groups. Progesterone did not decrease the frequency of preterm birth at ≤ 32 weeks. There was no difference between the groups with respect to the mean gestational age at delivery, infant morbidity or mortality or other maternal or neonatal outcome measures. Adverse events during the course of treatment were similar for the two groups. Conclusion Prophylactic treatment with vaginal progesterone did not reduce the frequency of recurrent preterm birth (≤ 32 weeks) in women with a history of spontaneous preterm birth. The effect of progesterone administration in patients at high risk for preterm delivery as determined by methods other than history alone (e.g. sonographic cervical length) requires further investigation. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

Abstract: There are three primary methods of gestational age estimation: dating based on last menstrual period (LMP), ultrasound-based dating and neonatal estimates. We review the strengths and limitations of each method as well as their implications for research. Dating based on LMP is a simple, low-cost method of estimating gestational age. Limitations associated with the use of menstrual-based dating include reporting problems such as uncertainty regarding the LMP date, possibly due to bleeding not associated with menses, as well as concerns about the incidence of delayed ovulation, which can result in invalid estimates of gestation, even for women with certain LMP dates. Given that most women in the US have at least one ultrasound during pregnancy, it is becoming increasingly common for clinicians to verify menstrual dates using early ultrasound. To calculate gestational age with the use of ultrasound, fetal measurements are compared with a gestational age-specific reference. The primary limitation of this method is the fact that the gestational age estimates of symmetrically large or small fetuses will be biased. Further, given that ultrasound references were developed using pregnancies that were dated according to reliable LMP dates, they are potentially biased in the same direction as dates calculated according to LMP. Neonatal estimates of gestational age have been shown to be the least precise dating method. To highlight the research implications of the choice of a gestational dating method, we used data from the Routine Antenatal Diagnostic Imaging with Ultrasound Study to identify risk factors for post-term delivery. Risk factors for post-term delivery are shown to vary according to the choice of a gestational dating method, suggesting that some findings are an artefact of the choice of a method rather than evidence of causality.

Abstract: Objective To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester. Methods This was a planned, but modified, secondary analysis of our multinational, multicenter, randomized, placebo-controlled trial, in which women were randomized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo. Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation. Treatment continued until either delivery, 37 weeks of gestation or development of preterm rupture of membranes. Maternal and neonatal outcomes were evaluated for the subset of all randomized women with cervical length < 28 mm at enrollment. The primary outcome was preterm birth at ≤ 32 weeks. Results A cervical length < 28 mm was identified in 46 randomized women: 19 of 313 who received progesterone and 27 of 307 who received the placebo. Baseline characteristics of the two groups were similar. In women with a cervical length < 28 mm, the rate of preterm birth at ≤ 32 weeks was significantly lower for those receiving progesterone than it was for those receiving the placebo (0% vs. 29.6%, P = 0.014). With progesterone, there were fewer admissions into the neonatal intensive care unit (NICU; 15.8% vs. 51.9%, P = 0.016) and shorter NICU stays (1.1 vs. 16.5 days, P = 0.013). There was also a trend toward a decreased rate of neonatal respiratory distress syndrome (5.3% vs. 29.6%, P = 0.060). Conclusion Vaginal progesterone may reduce the rate of early preterm birth and improve neonatal outcome in women with a short sonographic cervical length. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

Abstract: Background Maternal and fetal complications in pregnancies after renal transplantation have been highlighted in several reports, but information on their main predisposing factors is limited. The U.K. Transplant Pregnancy Registry was established in 1997 to obtain detailed information on pregnancies in female organ transplant recipients across the U.K. Methods For each female kidney, liver, or cardiothoracic organ transplant recipient who had had a recent pregnancy, data on maternal and fetal factors and pregnancy outcomes were collected using forms completed by their transplant follow-up and obstetric units. For kidney transplant recipients, the factors that influence pregnancy outcome were studied using logistic regression, and the effect of pregnancy on graft function was analyzed. Results There were live births in 83%, 69%, and 79% of pregnancies in cardiothoracic organ, liver, and kidney recipients, respectively. In 50% of live births from renal patients, delivery was preterm ( 150 micromol/L, a trend toward increased postpregnancy SCr was identified. Conclusions Pregnancy is likely to end in a live birth in a majority of organ transplant recipients. In patients with greater prepregnancy SCr and/or drug-treated hypertension during pregnancy, however, subsequent renal function may be adversely affected.

Abstract: Objective: The authors evaluated the effects of prenatal antidepressant exposure and maternal depression on infant gestational age at birth and risk of preterm birth. Method: Ninety women were followed in a prospective, naturalistic design through pregnancy with monthly assessments of symptoms of depression and anxiety using the Structured Clinical Interview for DSM-IV mood module for depression, the Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Perceived Stress Scale. Participants included 49 women with major depressive disorder who were treated with antidepressants during pregnancy (group 1), 22 women with major depressive disorder who were either not treated with antidepressants or had limited exposure to them during pregnancy (group 2), and 19 healthy comparison subjects (group 3). The primary outcome variables were the infants’ gestational age at birth, birth weight, 1- and 5-minute Apgar scores, and admission to the special care nursery. Results: Groups 1, 2, and 3 differe...

Abstract: Objective: To explore the association between antiretroviral therapy in pregnancy and premature delivery, birthweight, stillbirth and neonatal mortality, in pregnancies in HIV-infected women delivering between 1990 and 2005.Design: Pregnancies in women with diagnosed HIV infection in the UK and Ireland are notified to the National Study of HIV in Pregnancy and Childhood (NSHPC) through a well-established surveillance scheme.Results: The prematurity rate (< 37 weeks gestation) was higher in women on highly active antiretroviral therapy (HAART) (14.1%, 476/3384) than in women on mono/ dual therapy (10.1%, 107/1061), even after adjusting for ethnicity, maternal age, clinical status and injecting drug use as the source of HIV acquisition [adjusted odds ratio (AOR) = 1.51, 95% confidence interval (CI), 1.19-1.93; P = 0.001]. Delivery at < 35 weeks was even more strongly associated with HAART (AOR=2.34; 95% CI, 1.64-3.37; P < 0.001). The effect was the same whether or not HAART included a protease inhibitor. In comparison with exposure to mono/dual therapy, exposure to HAART was associated with lower birthweight standardized for gestational age (P < 0.001), and an increased risk of stillbirth (AOR = 2.27; 95% CI, 0.96-5.41; P = 0.063).Conclusions: These findings, based on comprehensive population surveillance, demonstrate an increased risk of prematurity associated with HAART, and a possible association with other perinatal outcomes, including stillbirth and birthweight. Although the beneficial effects of antiretroviral therapy on mother-to-child transmission are indisputable, monitoring antiretroviral therapy in pregnancy remains a priority. (C) 2007 Lippincott Williams & Wilkins.

Abstract: OBJECTIVE. Our goal was to investigate whether outcome in extremely low birth weight infants changes over time in Finland. PATIENTS AND METHODS. All infants with a birth weight < 1000 g born in Finland in 1996 - 1997 and 1999 - 2000 were included in the study. Perinatal and follow-up data were collected in a national extremely low birth weight infant research register. Data concerning cerebral palsy and visual impairment were obtained from hospitals, the national discharge, and visual impairment registers. RESULTS. A total of 529 and 511 extremely low birth weight infants were born during 1996 - 1997 and 1999 - 2000. No changes were detected in prenatal, perinatal, neonatal, and postneonatal mortality rates between the periods. The survival rates including stillborn infants were 40% and 44%. The incidence of respiratory distress syndrome and septicemia increased from 1996 - 1997 to 1999 - 2000 (75% vs 83% and 23% vs 31%). The overall incidence of intraventricular hemorrhage increased (29% vs 37%), but the incidence of intraventricular hemorrhage grades 3 through 4 did not (16% vs 17%). The rates of oxygen dependency at the age corresponding with 36 gestational weeks, retinopathy of prematurity stages 3 to 5, cerebral palsy, and severe visual impairment did not change. Mortality remained higher in 1 university hospital area during both periods compared with the other 4 areas, but no regional differences in morbidity were detected during the later period. CONCLUSIONS. No significant changes were detected in birth or mortality rate in extremely low birth weight infants born in Finland during the late 1990s, but some neonatal morbidities seemed to increase. Regional differences in mortality were detected in both cohorts. Repeated long-term follow-up studies on geographically defined very preterm infant cohorts are needed for establishing reliable outcome data of current perinatal care. Regional differences warrant thorough audits to assess causalities. (Less)

Abstract: The authors examined the associations of maternal smoking in pregnancy with various fetal growth characteristics among 7,098 pregnant women participating in the Generation R Study (2002-2006), a population-based prospective cohort study of pregnant women and their children in Rotterdam, the Netherlands. Maternal smoking was assessed by questionnaires administered in early, mid-, and late pregnancy. Fetal growth characteristics evaluated included head circumference, abdominal circumference, and femur length measured repeatedly in mid- and late pregnancy. Maternal smoking during pregnancy was associated with reduced growth in head circumference (-0.56 mm/week; 95% confidence interval (CI): -0.73, -0.40), abdominal circumference (-0.58 mm/week; 95% CI: -0.81, -0.34), and femur length (-0.19 mm/week; 95% CI: -0.23, -0.14). This reduced growth resulted in a smaller femur length from midpregnancy (gestational age 18-24 weeks) onwards and smaller head and abdominal circumferences from late pregnancy (gestational age ≥25 weeks) onwards. Analyses using standard deviation scores for the growth characteristics demonstrated the largest effect estimates for femur length. The authors concluded that maternal smoking during pregnancy is associated with reduced growth in fetal head circumference, abdominal circumference, and femur length. The larger effect on femur length suggests that smoking during pregnancy affects primarily peripheral tissues. Copyright

Abstract: This study examined the effects of being born very preterm on children's early language development using prospective longitudinal data from a representative regional cohort of 90 children born very preterm (gestational age <33 weeks and/or birth weight <1,500 grams) and a comparison sample of 102 children born full term (gestational age 38-41 weeks). The MacArthur-Bates Communicative Development Inventory: Words and Sentences (CDI-WS) was used to assess children's language development at age 2;0 (corrected for gestational age at birth). Clear linear relationships were found between gestational age at birth and later language outcomes, with decreasing gestational age being associated with poorer parent-reported language skills. Specifically, children born extremely preterm (<28 weeks' gestation) tended to perform less well than those born very preterm (28-32 weeks' gestation), who in turn performed worse than children born full term (38-41 weeks' gestation). This pattern of findings was evident across a range of outcomes spanning vocabulary size and quality of word use, as well as morphological and syntactic complexity. Importantly, associations between gestational age at birth and language outcomes persisted after statistical control for child and family factors correlated with both preterm birth and language development. These findings demonstrate the presence of pervasive delays in the early language development of children born very preterm. They also highlight the importance of gestational age in predicting later language risk in this population of infants.

Abstract: OBJECTIVE. Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS. Infants who were born at <32 weeks of gestation and/or with a birth weight of <1500 g in the Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants) were reexamined at age 19. Outcomes were adjusted for nonrespondents using multiple imputation and categorized into none, mild, moderate, or severe problems. RESULTS. Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have ≥3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had ≥1 moderate or severe problems in the assessed areas. CONCLUSIONS. A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19. Copyright © 2007 by the American Academy of Pediatrics.

Abstract: BACKGROUND Azathioprine (AZP) interferes with nucleic acid synthesis and is teratogenic in animals. In view of the paucity of information on the use of AZP during pregnancy we investigated this subject in a prospective, controlled, multicenter study. Our objective was too determine whether exposure to AZP during pregnancy increases the risk for major malformations and to determine the effect on pregnancy outcome. METHODS Pregnant women on AZP who contacted one of seven teratogen information services were compared to a cohort of pregnant women who contacted two of the seven teratogen information services and took nonteratogenic treatments during their pregnancy. RESULTS Follow-up was completed on 189 women in the AZP group and compared to 230 women in the control group. The rate of major malformations did not differ between groups with six neonates in each; the AZP rate was 3.5% and the control group rate was 3.0% (p = .775; OR 1.17; CI: 0.37, 3.69). The mean birth weight and gestational age were lower in the AZP group (2,995 g vs. 3,252 g [p = .001, difference of mean: 257, 95% CI: 106.3, 408.1] and 37.8 weeks vs. 39.1 weeks [p = .001, difference of mean: 1.3, 95% CI: .5, 2.0], respectively). The AZP group had more cases of prematurity (21.4% vs. 5.2% [p < .001; OR 4.0; 95% CI: 2.0, 8.06]) and low birth weight (23% vs. 6.0% [p < .001; OR 3.81; 95% CI: 2.0, 7.2]). CONCLUSIONS These results suggest that AZP (50–100 mg/day) does not triple the rate of birth defects; however, it is associated with lower birth weight, gestational age, and prematurity. Larger studies are needed to confirm these observations. © 2007 Wiley-Liss, Inc.