Abstract: Objectives. To determine the mortality and morbidity for infants weighing 401 to 1500 g (very low birth weight [VLBW]) at birth by gestational age, birth weight, and gender. Study Design. Perinatal data were collected prospectively on an inborn cohort from January 1995 through December 1996 by 14 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports. Sociodemographic factors, perinatal events, and the neonatal course to 120 days of life, discharge, or death were evaluated. Results. Eighty four percent of 4438 infants weighing 501 to 1500 g at birth survived until discharge to home or to a long-term care facility (compared with 80% in 1991 and 74% in 1988). Survival to discharge was 54% for infants 501 to 750 g at birth, 86% for those 751 to 1000 g, 94% for those 1001 to 1250 g, and 97% for those 1251 to 1500g. The incidence of chronic lung disease (CLD; defined as receiving supplemental oxygen at 36 weeks9 postmenstrual age; 23%), proven necrotizing enterocolitis (NEC; 7%), and severe intracranial hemorrhage (ICH; grade III or IV; 11%) remained unchanged between 1991 and 1996. Furthermore, 97% of all VLBW infants and 99% of infants weighing Mortality for 195 infants weighing 401 to 500 g was 89%, with nearly all survivors developing CLD. Mortality in infants weighing 501 to 600 g was 71%; among survivors, 62% had CLD, 35% had severe ICH, and 15% had proven NEC. Conclusions. Survival for infants between 501 and 1500 g at birth continued to improve, particularly for infants weighing

Abstract: Objective To determine the value of transvaginal color Doppler assessment of the uterine arteries at 23 weeks of gestation in predicting the subsequent development of pre-eclampsia and fetal growth restriction. Patients and methods Women with singleton pregnancies attending for routine ultrasound examination at 23 weeks in any one of seven hospitals underwent Doppler assessment of the uterine arteries. The presence of an early diastolic notch in the waveform was noted, and the mean pulsatility index of the two arteries was calculated. Screening characteristics in the prediction of pre-eclampsia and the delivery of a low birth-weight infant were calculated. Results Doppler examination of the uterine arteries was attempted in 8335 consecutive singleton pregnancies, satisfactory waveforms were obtained from both vessels in 8202 (98.4%) cases and complete outcome data were available in 7851 (95.7%) of these. The mean gestational age was 23 (range, 22–24) weeks. The mean uterine artery pulsatility index did not change significantly with gestation (r = –0.0078; P = 0.483); the median value was 1.04 and the 95th centile was 1.63. In 9.3% of cases early diastolic notches in the waveform from both uterine arteries were present and in an additional 11.1% of cases there were notches unilaterally. Pre-eclampsia with fetal growth restriction occurred in 42 (0.5%) cases, pre-eclampsia without fetal growth restriction in 71 (0.9%) and fetal growth restriction without pre-eclampsia in 698 (8.9%). The sensitivity of increased pulsatility index above the 95th centile (1.63) for pre-eclampsia with fetal growth restriction was 69%, for pre-eclampsia without fetal growth restriction was 24%, for fetal growth restriction without pre-eclampsia was 13%, for pre-eclampsia irrespective of fetal growth restriction was 41% and for fetal growth restriction irrespective of pre-eclampsia was 16%. The sensitivity of fetal growth restriction defined by the 5th rather than the 10th centile was higher (19% vs. 16%). The sensitivity for both pre-eclampsia and fetal growth restriction was inversely related to the gestational age at delivery; when delivery occurred before 32 weeks, the sensitivity for all cases of pre-eclampsia with fetal growth restriction, pre-eclampsia without fetal growth restriction and fetal growth restriction without pre-eclampsia increased to 93%, 80% and 56%, respectively. The sensitivity of bilateral notches in predicting pre-eclampsia and/or fetal growth restriction was similar to that of increased pulsatility index but the screen-positive rate with notches (9.3%) was much higher than that with increased pulsatility index (5.1%).

Abstract: Oral Conditions and Pregnancy (OCAP) is a 5-year prospective study of pregnant women designed to determine whether maternal periodontal disease contributes to the risk for prematurity and growth restriction in the presence of traditional obstetric risk factors. Full-mouth periodontal examinations were conducted at enrollment (prior to 26 weeks gestational age) and again within 48 hours postpartum to assess changes in periodontal status during pregnancy. Maternal periodontal disease status at antepartum, using a 3-level disease classification (health, mild, moderate-severe) as well as incident periodontal disease progression during pregnancy were used as measures of exposures for examining associations with the pregnancy outcomes of preterm birth by gestational age (GA) and birth weight (BW) adjusting for race, age, food stamp eligibility, marital status, previous preterm births, first birth, chorioamnionitis, bacterial vaginosis, and smoking. Interim data from the first 814 deliveries demonstrate that maternal periodontal disease at antepartum and incidence/progression of periodontal disease are significantly associated with a higher prevalence rate of preterm births, BW < 2,500 g, and smaller birth weight for gestational age. For example, among periodontally healthy mothers the unadjusted prevalence of births of GA < 28 weeks was 1.1%. This was higher among mothers with mild periodontal disease (3.5%) and highest among mothers with moderate-severe periodontal disease (11.1%). The adjusted prevalence rates among GA outcomes were significantly different for mothers with mild periodontal disease (n = 566) and moderate-severe disease (n = 45) by pair-wise comparisons to the periodontally healthy reference group (n = 201) at P = 0.017 and P < 0.0001, respectively. A similar pattern was seen for increased prevalence of low birth weight deliveries among mothers with antepartum periodontal disease. For example, there were no births of BW < 1000 g among periodontally healthy mothers, but the adjusted rate was 6.1% and 11.4% for mild and moderate-severe periodontal disease (P = 0.0006 and P < 0.0001), respectively. Periodontal disease incidence/progression during pregnancy was associated with significantly smaller births for gestational age adjusting for race, parity, and baby gender. In summary, the present study, although preliminary in nature, provides evidence that maternal periodontal disease and incident progression are significant contributors to obstetric risk for preterm delivery, low birth weight and low weight for gestational age. These studies underscore the need for further consideration of periodontal disease as a potentially new and modifiable risk for preterm birth and growth restriction.

Abstract: Background Previous studies have suggested that chronic periodontal infection may be associated with preterm births. The authors conducted a prospective study to test for this association. Methods A total of 1,313 pregnant women were recruited from the Perinatal Emphasis Research Center at the University of Alabama at Birmingham. Complete periodontal, medical and behavioral assessments were made between 21 and 24 weeks gestation. After delivery, medical records were consulted to determine each infant's gestational age at birth. From these data, the authors calculated relationships between periodontal disease and preterm birth, while adjusting for smoking, parity (the state or fact of having born offspring), race and maternal age. Results were expressed as odds ratios and 95 percent confidence intervals, or CIs. Results Patients with severe or generalized periodontal disease had adjusted odds ratios (95 percent CI) of 4.45 (2.16–9.18) for preterm delivery (that is, before 37 weeks gestational age). The adjusted odds ratio increased with increasing prematurity to 5.28 (2.05–13.60) before 35 weeks' gestational age and to 7.07 (1.70–27.4) before 32 weeks' gestational age. Conclusions The authors' data show an association between the presence of periodontitis at 21 to 24 weeks' gestation and subsequent preterm birth. Further studies are needed to determine whether periodontitis is the cause. Clinical Implications While this large prospective study has shown a significant association between preterm birth and periodontitis at 21 to 24 weeks' gestation, neither it nor other studies to date were designed to determine whether treatment of periodontitis will reduce the risk of preterm birth. Pending an answer to this important question, it remains appropriate to advise expectant mothers about the importance of good oral health.

Abstract: UNLABELLED This 8th Swedish population-based cerebral palsy (CP) report comprises 241 children born 1991-94. The live birth prevalence was 2.12 per 1000. Excluding 7 postnatally-derived cases, the gestational age-specific prevalences were 86 for extremely preterm children, 60 for very preterm and 6 for moderately preterm, and 1.3 for term children per 1000. Spastic hemiplegic, diplegic and tetraplegic subtypes accounted for 33%, 44% and 6%, dyskinetic CP for 12% and simple ataxia for 4%. Neuroimaging had been performed in 90%. Probable aetiology was identified in 73% of preterm and 86% of term children. Among preterm children it was considered prenatal in 12%, peri/neonatal in 61% and unclassifiable in 27%, while it was 51%, 36% and 14% among term children. CONCLUSION The live birth prevalence for CP in the birth year period 1991-94 continued to decrease slightly. Gestational age-specific prevalences increased marginally in extremely and very preterm births, continued to decrease in moderately preterm births and decreased slightly in term births. Probable aetiology and timing of the brain insult could be revealed in 81%, birth asphyxia being the likely cause in 28% of term children.

Abstract: Objective To examine the value of uterine artery Doppler at 11–14 weeks of gestation in the identification of women at risk of developing pre-eclampsia and fetal growth restriction. Methods Uterine artery Doppler was carried out at 11– 14 weeks in 3324 consecutive singleton pregnancies attending for routine care in three London hospitals. The right and left uterine arteries were identified using color flow mapping and velocity waveforms were obtained using pulsed Doppler. The mean pulsatility index of the two arteries was determined and the predictive value of a mean pulsatility index > the 95th centile in the prediction of pre-eclampsia and/or fetal growth restriction was calculated. Results Satisfactory flow velocity waveforms were obtained from both uterine arteries in 3195 (96.1%) of the 3324 pregnancies examined and complete outcome information was obtained for 3045 (95.3%) of these women. The 95th centile of the uterine artery mean pulsatility index was 2.35 and did not change significantly with gestational age. The pregnancy was complicated by pre-eclampsia in 63 (2.1%) cases and by fetal growth restriction in 290 (9.5%) cases. The sensitivity of a mean pulsatility index > 2.35 for pre-eclampsia (with or without fetal growth restriction) was 27.0% but for fetal growth restriction alone it was 11.7%. The respective sensitivities for these complications requiring delivery before 32 weeks of gestation were 60.0% and 27.8%, respectively. Conclusion Uterine artery Doppler at 11–14 weeks of gestation identifies a high proportion of women who develop severe pre-eclampsia and/or fetal growth restriction.

Abstract: Objective. This study examines the relationship of intrauterine growth, measured by size and maturity at birth, to age at menarche, while also considering a wide range of other factors that may affect maturation. The research is motivated by the current debate about the importance of the prenatal environment as a determinant of later disease risk. Methods. Data were collected during the Cebu Longitudinal Health and Nutrition Survey. This community-based study has followed a cohort of several thousand Filipino infants since their birth in 1983 to 1984. Participants live in urban and rural communities of Metro Cebu, the second largest metropolitan area of the Philippines. The analysis sample includes 997 girls 14 to 15 years of age. The main outcome measure is age at menarche, determined from girls9 self-report of the month and year of first menses. Factors that influenced age at menarche were identified using Weibull parametric survival time models. The main exposure variables of interest included weight and length (measured by trained field staff) and gestational age (assessed from mother9s reported date of last menstrual period, augmented by clinical assessments at birth). The analysis also takes into account a wide range of other factors that are likely to affect age at menarche. These include the girls9 early postnatal growth rates, premenarcheal body composition (body mass index and skinfold thicknesses measured at 8 years), current diet (measured by two 24-hour dietary recalls), and socioeconomic conditions of the household in which they live. We also assessed the contribution of maternal characteristics, including age at menarche, height, and nutritional status while pregnant with the study child. Results. The median age at menarche calculated from the hazard model is 13.1 years, with 50% of girls attaining menarche between 12.4 and 13.9 years. Earlier menarche is characteristic of girls who live in urban, higher socioeconomic status households, as indicated by higher maternal education, better housing quality, and possession of assets, such as a TV or refrigerator. Age at menarche is significantly associated with birth characteristics. Although birth weight alone was not significantly related to age at menarche, girls who were relatively long and thin at birth (>49 cm, Conclusions. The study provides additional evidence of fetal programming of later health outcomes by showing that future growth and maturation trajectories are established in utero. Furthermore, rapid postnatal growth potentiates the effects of size at birth and is related independently to earlier pubertal maturation.

Abstract: Objective: Our purpose was to examine pregnancy outcomes among women age 40 or older. Methods: Between January, 1997 and December 1999, we performed a case-control study compared pregnancy outcomes of 468 patients delivered at our hospital at > Or = 40 years old with outcomes in a control group consisting of the next two deliveries of women with ages 20 to 29 years. Retrospective analysis of the antepartum and intrapartum records was done to compare clinical outcome. Results: Approximately 25,356 women delivered during the study period, and 468 (1.8%). Of these women were at age 40 or older. Of this latter group, 50 (10.7%) were nulliparous. Mean birthweight of infants delivered by older nulliparous women was significantly lower than that among nulliparous controls (3210 ± 5 vs. 3320 ± 1 g), whereas mean birth weight in the group of older multiparous was not different than that among younger multiparous controls (3370 ± 1 vs. 3365 ± 4 g). Gestational age at delivery was significantly lower among older nulliparous, and multiparous compared with nulliparous and multiparous younger controls. Older women were at increased risk for cesarean delivery (nulliparous 18%; multiparous 14%) compared with nulliparous and multiparous younger control groups (nulliparous 8%; multiparous 6%). In the study group, the operative vaginal delivery rate was higher than that of the control group. The study groups were more likely to develop gestational diabetes, preeclampsia, and placenta praevia. Older nulliparous had an increased incidence of malpresentation, abnormal labour patterns, special care baby unit admission (SCBU), and low 1-minute Apgar score. Older multiparous were more likely to experience birth asphyxia, premature rupture of membranes, and antepartum vaginal bleeding. Conclusion: Nulliparous women age 40 or over have a higher risk of operative delivery than do youngr nulliparous women. This increase occurs in spite of lower birth weight and gestational age and may be explained by the increase incidence of obstetric complications. Although maternal morbidity was increased in the older women, the overall neonatal outcome did not appear to be affected.

Abstract: Clinical data from the first 812 deliveries from a cohort study of pregnant mothers entitled Oral Conditions and Pregnancy (OCAP) demonstrate that both antepartum maternal periodontal disease and incidence/progression of periodontal disease are associated with preterm birth and growth restriction after adjusting for traditional obstetric risk factors. In the current study we present measures of maternal periodontal infection using whole chromosomal DNA probes to identify 15 periodontal organisms within maternal periodontal plaque sampled at delivery. In addition, maternal postpartum IgG antibody and fetal exposure, as indexed by fetal cord blood IgM level to these 15 maternal oral pathogens, was measured by whole bacterial immunoblots. The potential role of maternal infection with specific organisms within 2 bacterial complexes most often associated with periodontitis, conventionally termed "Orange" (Campylobacter rectus, Fusobacterium nucleatum, Peptostreptococcus micros, Prevotella nigrescens, and Prevotella intermedia) and "Red" (Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola) complexes, respectively, to prematurity was investigated by relating the presence of oral infection, maternal IgG, and fetal cord IgM, comparing full-term to preterm (gestational age < 37 weeks). The prevalence of 8 periodontal pathogens was similar among term and preterm mothers at postpartum. There was a 2.9-fold higher prevalence of IgM seropositivity for one or more organisms of the Orange or Red complex among preterm babies, as compared to term babies (19.9% versus 6.9%, respectively, P = 0.0015, chi square). Specifically, the prevalence of positive fetal IgM to C. rectus was significantly higher for preterm as compared to full-term neonates (20.0% versus 6.3%, P = 0.0002, as well as P. intermedia (8.8% versus 1.1%, P = 0.0003). A lack of maternal IgG antibody to organisms of the Red complex was associated with an increased rate of prematurity with an odds ratio (OR) = 2.2; confidence interval (CI) 1.48 to 3.79), consistent with the concept that maternal antibody protects the fetus from exposure and resultant prematurity. The highest rate of prematurity (66.7%) was observed among those mothers without a protective Red complex IgG response coupled with a fetal IgM response to Orange complex microbes (combined OR 10.3; P < 0.0001). These data support the concept that maternal periodontal infection in the absence of a protective maternal antibody response is associated with systemic dissemination of oral organisms that translocate to the fetus resulting in prematurity. The high prevalence of elevated fetal IgM to C. rectus among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.

Abstract: Aim—To identify incidence of school and behaviour problems at age 7 years in children born between 32 and 35 weeks gestation,and investigate perinatal risk factors. Method—The study population consisted of all children born at 32‐35 weeks gestation to mothers resident in Oxfordshire in l990. General practitioners, parents, and teachers were asked about health, behaviour, and education by postal questionnaire. Teachers rated children on level of function in six areas using a five point scale. They also completed the Strengths and DiYculties behaviour questionnaire. Perinatal risk factors were identified for children with poor school performance using a univariate and multivariate analysis. Results—Teacher responses were obtained for 117 (66%) of the 176 children in the cohort. Twenty nine (25%) required support from a non-teaching assistant, five (4%) had required a statement of special educational needs, and three (3%) were at special school. Poor outcome was reported for 32% in writing, 31% in fine motor skills, 29% in mathematics, 19% in speaking, 21% in reading, and 12% in physical education. On the behaviour questionnaire, 19% of the cohort achieved an abnormal hyperactivity score (population norm 10%). Multivariate analysis showed perinatal variables that remained significant, independent of other variables; they were discharge from the special care baby unit > 36 weeks postconceptional age (odds ratio 4.15; 95% confidence interval 1.43 to 12.05) and male sex (odds ratio 3.88; 95% confidence interval 1.42 to 10.6). Conclusion—Up to a third of children born between 32 and 35 weeks gestation may have school problems. As there are larger numbers in this gestational category compared with smaller babies, this finding has implications for educational services. (Arch Dis Child Fetal Neonatal Ed 2001;85:F23‐F28)

Abstract: Background. Management of pain in very low birth weight infants is limited by a lack of empiric knowledge about the multiple determinants of biobehavioral reactivity in infants receiving neonatal intensive care. Objective. To examine relationship of early neonatal factors and previous medication exposure to subsequent biobehavioral reactivity to acute pain of blood collection. Design. Prospective cohort study. Methods. One hundred thirty-six very low birth weight (≤1500 g) infants who underwent heel lance for blood collection at 32 weeks9 postconceptional age formed the study sample, after excluding those with significant cerebral lesions (periventricular leukomalacia or cerebral parenchymal infarction [grade 4 intraventricular hemorrhage]) on cranial ultrasound. Pain reactions were assessed using the Neonatal Facial Coding System, infant state, and spectral analysis of change in heart rate variability from baseline to reaction to invasive stimulation. Factor analysis was used to provide an empirical basis for deriving summary pain scores, one factor was primarily behavioral and the other primarily autonomic. Results. A normal reaction to procedural pain is characterized by facial grimacing and heightened cardiac sympathetic activity. The most significant factors associated with altered behavioral and autonomic pain reactivity at 32 weeks9 postconceptional age were a greater number of previous invasive procedures since birth and gestational age (GA) at birth, both of which were related to a dampened response. After controlling for these variables, exogenous steroid exposure made an independent contribution to both the behavioral and autonomic pain scores, also in the direction of dampening the response. Conversely, previous exposure to morphine was associated with “normalized” (ie, increased) rather than diminished responses. In addition, higher mean heart rate at baseline was associated with lower GA at birth and longer time on mechanical ventilation. Conclusion. Early pain exposure at very low GA may alter the autonomic substrate, resulting in infants who are in a perpetual state of stress. The results of this study suggest that the judicious use of analgesia may ameliorate these effects on later pain reactivity. However, although early morphine exposure may “normalize” subsequent pain reaction, this study did not examine its effects on neurodevelopment.

Abstract: Paired fetal and maternal samples were obtained, at fetal blood sampling and intrauterine transfusion, to study hypothalamic-pituitary-adrenal stress responses. This confirmed that the fetus mounts an hypothalamic-pituitary-adrenal stress response to transfusion via the intrahepatic vein, which involves piercing the fetal trunk, but not to transfusion via the placental cord insertion [mean cortisol response via intrahepatic vein delta = 52.6 nmol/L, 95% CI (25.3-79.9), P = 0.001; mean beta-endorphin response delta =106 pg/mL, 95% CI (45.3-167), P = 0.002]. Baseline maternal fetal ratios were 13 [95% CI (10.7-15.2)] for cortisol and 0.8 [95% CI (0.5-1.0)] for beta-endorphin. The novel findings were: 1) that the fetal responses were independent of those of the mother, which did not change during transfusion at either site; 2) that there was a correlation between baseline fetal and maternal cortisol levels (r = 0.58, n = 51, P < 0.0001) but not between baseline fetal and maternal ss-endorphin levels, suggesting cortisol transfer across the placenta, rather than joint control by placental CRH; and 3) that fetal beta-endorphin responses were apparent from 18 weeks gestation and independent of gestational age, whereas fetal cortisol responses were apparent from 20 weeks gestation and were dependent on gestational age (y = -91.4 + 5.08x, r = 0.51; n = 16; P = 0.04; CI for slope, 0.16-10.0), consistent with the maturation of the fetal pituitary before the fetal adrenal.

Abstract: Objectives. To determine the changes with postnatal age for survival, with and without major sensorineural disability, to 5 years of age in very preterm infants and to contrast their prognosis with normal birth weight (NBW) control participants. Methods. A geographically determined cohort study was conducted in Victoria, Australia. Consecutive live births of 23 to 27 weeks9 gestational age born during 1991 to 1992 and randomly selected contemporaneous NBW control participants were studied. The main outcome measures were survival and rates of major disability at 5 years of age, determined for those offered intensive care, after day 7, after day 28, and at hospital discharge. Results. Of 401 live births of 23 to 27 weeks9 gestation, 225 (56.1%) survived to 5 years of age. The survival rate rose significantly with increasing gestational age at birth in those offered intensive care and by day 7 but not by day 28. The survival rate free of major disability rose significantly with increasing gestational age at all postnatal ages but was not an independent predictive variable by day 28; other adverse events were more important. In the absence of adverse events, the rate of survival free of major disability for very preterm infants who had survived to discharge was 93.2%, similar to the rate of 95.5% for NBW control participants. Conclusions. The prognosis for very preterm infants changes substantially with postnatal age. Counseling of families should be repeated at intervals, and the advice offered should vary with perinatal events.

Abstract: Umbilical cord blood (CB) is a useful stem cell source for patients without matched family donors. CB banking is expensive, however, because only a small percentage of the cord units stored are used for transplantation. In this study, we determined whether maternal factors, such as race, age, and smoking status have an effect on laboratory parameters of hematopoietic potential, such as viability, cell counts, CD34+ cell counts, and CFU-GM. We studied the effect of neonatal characteristics such as birth order, birth weight, gestational age, and sex of the baby on the same laboratory parameters. Race and maternal age had no effect on these laboratory parameters. In multivariate analysis, babies of longer gestational age had higher cell counts, but lower CD34+ cell counts and CFU-GM. Bigger babies had higher cell counts, more CD34+ cells, and more CFU-GM. Women with fewer previous live births also produced cord units with higher cell counts, CFU-GM, and CD34+ cell counts. Specifically, each 500 g increase in birth weight contributed to a 28% increase in CD34+ cell counts, each week of gestation contributed to a 9% decrease in CD34+cell counts, and each previous birth contributed to a 17% decrease in CD34+ cell counts (all P < 0.05). These data may be used to select the optimal cord blood donors and allow CB banks efficient resource allocation. Bone Marrow Transplantation (2001) 27, 7–14.

Abstract: We prospectively studied pregnancy outcome in 428 women with gestational diabetes mellitus (DM) and 196 women with pregestational DM, with particular reference to the influence of maternal obesity and excessive weight gain. These were consecutive singleton pregnancies delivered in our institution over 5 years. After controlling for multiple risk factors, including maternal BMI and pregnancy weight gain, women with pregestational DM were at increased risk (compared to those with gestational DM) for Caesarean delivery (OR 3.6, 95%CI 2.3-5.6), shoulder dystocia or cephalopelvic disproportion (OR 2.2, 95%CI 1.3-3.6), and gestational hypertension or toxaemia (OR 3.0, 95%CI 1.7-5.4). The offspring of these women were also at increased risk for admission to the neonatal intensive care unit (OR 4.0, 95%CI 2.3-6.8), large-for-gestational-age birthweight (OR 3.5, 95%CI 2.2-5.6), and preterm birth before 37 weeks (OR 3.8, 95%CI 2.5-5.9). Maternal obesity, and, to a lesser degree, excessive weight gain, were also independent risk factors for all these adverse maternal and neonatal outcomes, regardless of the type of DM, except for shoulder dystocia/cephalopelvic disproportion.

Abstract: OBJECTIVE: Because there are no studies available on the safety of venlafaxine during pregnancy, the authors’ goal in this study was to determine whether venlafaxine increases the risk for major malformations. METHOD: Data on 150 women exposed to venlafaxine during pregnancy in seven pregnancy counseling centers were compared with data from studies of pregnant women who 1) received selective serotonin reuptake inhibitor antidepressants (SSRIs) (N=150) and 2) who received nonteratogenic drugs (N=150). RESULTS: Among the 150 women who were exposed to venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions, and seven had therapeutic abortions; two of the babies had major malformations. There were no significant differences between these women and the two comparison groups on any of the measures analyzed. CONCLUSIONS: These results suggest that the use of venlafaxine during pregnancy does not increase the rates of major malformations above the baseline rate of 1%–3%.

Abstract: Background Recent studies suggest that small newborns who present rapid postnatal growth may have an increased risk of chronic diseases in adulthood. On the other hand, it is widely assumed that catch-up growth is desirable for low birthweight children, but the literature on this subject is limited. Methods Population-based cohort study in southern Brazil, with 3582 children examined at birth, 20 and 42 months of age. Catch-up growth from 0 to 20 months was related to subsequent risks of hospital admissions and mortality. Results Children who were small-for-gestational-age (SGA) but presented substantial weight gain (>0.66 z-score) up to the age of 20 months had 65% fewer subsequent hospital admissions than other SGA children (5.6% versus 16.0%; P , 0.001). Mortality to age 5 years was 75% lower (3 versus 13 per 1000, a non-significant difference based on a small number of deaths) for rapid-growing SGA children compared to the remaining SGA children. Their admission and mortality rates were similar to those observed for children born with an appropriate birthweight for their gestational age (AGA). Similar positive effects of rapid growth were found for AGA children. Conclusion There appear to be definite benefits associated with catch-up growth. Growth promotion efforts for infants who are born small should take into account their possible short- and long-term consequences.

Abstract: OBJECTIVE —To determine the influence of microalbuminuria on pregnancy outcome in women with type 1 diabetes RESEARCH DESIGN AND METHODS —This prospective cohort study took place at the Obstetric Clinic at National University Hospital, Copenhagen, from January 1996 to February 2000 All Caucasian women with type 1 diabetes, unselected from the eastern part of Denmark, with a living fetus before 17 weeks of gestation on admission were asked to participate For women with more than one delivery in the study period, only the first pregnancy was included Of the remaining 246 women, 240 (98%) entered the study They were categorized according to their urinary albumin excretion (normal urinary albumin excretion, 300 mg/24 h) before pregnancy or in the first trimester RESULTS —A total of 203 women (85%) had normal urinary albumin excretion, 26 (11%) had microalbuminuria, and 11 (5%) had diabetic nephropathy Mean HbA 1c at 2–6 weeks was 75% (SD 11), 81 (09), and 88 (13) ( P P P P P 1c at 2–6 weeks ( P CONCLUSIONS —The prevalence of preterm delivery is considerably increased in women with microalbuminuria, mainly caused by preeclampsia Classification according to urinary albumin excretion and metabolic control around the time of conception are superior to the White classification in predicting preterm delivery in women with type 1 diabetes

Abstract: Aims/hypothesis. Insulin resistance as well as marked changes in body weight and energy metabolism are associated with pregnancy. Its impact on plasma leptin is not known and was determined in this longitudinal study in both diabetic and normal pregnancy. Methods. At 28 gestational weeks plasma concentrations of leptin and B-cell hormones were measured at fasting and after an oral glucose load (OGTT:75 g) in women with gestational diabetes and pregnant women with normal glucose tolerance and compared with women who were not pregnant (C). Results. Plasma leptin (ng/ml) was higher (p < 0.001) in women with gestational diabetes (24.9 ± 1.6) than in women with normal glucose tolerance (18.2 ± 1.5) and increased in both groups when compared with the non-pregnant women (8.2 ± 1.3; p < 0.0005). No change in plasma leptin concentrations was induced by OGTT in any group. Basal insulin release was higher (p < 0.05) in women with gestational diabetes compared with the pregnant women with normal glucose tolerance. Marked insulin resistance was confirmed by a 20 % lower (p < 0.05) insulin sensitivity in subgroup analysis and a decrease of almost 40 % in fasting glucose/insulin ratio (p < 0.005) in women with gestational diabetes. Leptin correlated in women with gestational diabetes with basal plasma concentrations of glucose (p < 0.02), insulin (p < 0.004) and proinsulin (p < 0.01) as well as with BMI (p < 0.001) and overall pregnancy induced maternal weight gain (p < 0.009). With normalisation of blood glucose 8 weeks after delivery in women with gestational diabetes their plasma leptin decreased (p < 0.0005) to 17.3 ± 1.9 ng/ml but did not completely normalize (p < 0.05 vs non-pregnant women). Conclusion/interpretation. Our data show that women with gestational diabetes without any change in plasma leptin upon oral glucose loading have increased plasma leptin concentrations during and after pregnancy, a clear association of plasma leptin with the respective concentration of glucose and insulin resistance as well as with changes in body weight, and a failure to normalize spontaneously BMI to the same extent as pregnant women with normal glucose tolerance when compared with matched control subjects. [Diabetologia (2001) 44: 164–172]