Effects of the neonatal intensive care environment on circadian health and development of preterm infants.

The circadian system in mammals ensures adaptation to the light-dark cycle on Earth and imposes 24-h rhythmicity on metabolic, physiological and behavioral processes. The central circadian pacemaker is located in the brain and is entrained by environmental signals called Zeitgebers. From here, neural, humoral and systemic signals drive rhythms in peripheral clocks in nearly every mammalian tissue. During pregnancy, disruption of the complex interplay between the mother's rhythmic signals and the fetal developing circadian system can lead to long-term health consequences in the offspring. When an infant is born very preterm, it loses the temporal signals received from the mother prematurely and becomes totally dependent on 24/7 care in the Neonatal Intensive Care Unit (NICU), where day/night rhythmicity is usually blurred. In this literature review, we provide an overview of the fetal and neonatal development of the circadian system, and short-term consequences of disruption of this process as occurs in the NICU environment. Moreover, we provide a theoretical and molecular framework of how this disruption could lead to later-life disease. Finally, we discuss studies that aim to improve health outcomes after preterm birth by studying the effects of enhancing rhythmicity in light and noise exposure.

Maternal iron status in early pregnancy and DNA methylation in offspring: an epigenome-wide meta-analysis.

BACKGROUND: Unbalanced iron homeostasis in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism linking environmental exposures such as micronutrient status during pregnancy with offspring health. We performed a meta-analysis on the association of maternal early-pregnancy serum ferritin concentrations, as a marker of body iron stores, and cord blood DNA methylation. We included 1286 mother-newborn pairs from two population-based prospective cohorts. Serum ferritin concentrations were measured in early pregnancy. DNA methylation was measured with the Infinium HumanMethylation450 BeadChip (Illumina). We examined epigenome-wide associations of maternal early-pregnancy serum ferritin and cord blood DNA methylation using robust linear regression analyses, with adjustment for confounders and performed fixed-effects meta-analyses. We additionally examined whether associations of any CpGs identified in cord blood persisted in the peripheral blood of older children and explored associations with other markers of maternal iron status. We also examined whether similar findings were present in the association of cord blood serum ferritin concentrations with cord blood DNA methylation. RESULTS: Maternal early-pregnancy serum ferritin concentrations were inversely associated with DNA methylation at two CpGs (cg02806645 and cg06322988) in PRR23A and one CpG (cg04468817) in PRSS22. Associations at two of these CpG sites persisted at each of the follow-up time points in childhood. Cord blood serum ferritin concentrations were not associated with cord blood DNA methylation levels at the three identified CpGs. CONCLUSION: Maternal early-pregnancy serum ferritin concentrations were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.

Early Ultrasonic Monitoring of Brain Growth and Later Neurodevelopmental Outcome in Very Preterm Infants.

BACKGROUND AND PURPOSE: In infants born very preterm, monitoring of early brain growth could contribute to prediction of later neurodevelopment. Therefore, our aim was to investigate associations between 2 early cranial ultrasound markers (corpus callosum-fastigium and corpus callosum length) and neurodevelopmental outcome and the added value of both markers in the prediction of neurodevelopmental outcome based on neonatal risk factors and head circumference in very preterm infants. MATERIALS AND METHODS: This prospective observational study included 225 infants born at <30 weeks' gestational age, of whom 153 were without any brain injury on cranial ultrasound. Corpus callosum-fastigium and corpus callosum length and head circumference were measured at birth, 29 weeks' gestational age, transfer from the neonatal intensive care unit to a level II hospital, and 2 months' corrected age. We analyzed associations of brain markers and their growth with cognitive, motor, language, and behavioral outcome at 2 years' corrected age. RESULTS: In infants without brain injury, greater corpus callosum-fastigium length at 2 months was associated with better cognitive outcome. Corpus callosum length at 2 months was positively associated with cognitive, motor, and language outcome. Faster growth of the corpus callosum length between birth and 2 months was associated with better cognitive and motor function. Prediction of neurodevelopmental outcome based on neonatal risk factors with or without head circumference was significantly improved by adding corpus callosum length. CONCLUSIONS: Both corpus callosum-fastigium and corpus callosum length on cranial ultrasound are associated with neurodevelopmental outcome of very preterm infants without brain injury at 2 years, but only corpus callosum length shows the added clinical utility in predicting neurodevelopmental outcome.

Role of Multichance Fission in the Description of Fission-Fragment Mass Distributions at High Energies.

Fission-fragment mass distributions were measured for ^{237-240}U, ^{239-242}Np, and ^{241-244}Pu populated in the excitation-energy range from 10 to 60 MeV by multinucleon transfer channels in the reaction ^{18}O+^{238}U at the Japan Atomic Energy Agency tandem facility. Among them, the data for ^{240}U and ^{240,241,242}Np were observed for the first time. It was found that the mass distributions for all the studied nuclides maintain a double-humped shape up to the highest measured energy in contrast to expectations of predominantly symmetric fission due to the washing out of nuclear shell effects. From a comparison with the dynamical calculation based on the fluctuation-dissipation model, this behavior of the mass distributions was unambiguously attributed to the effect of multichance fission.

Foetal fractional thigh volume: an early 3D ultrasound marker of neonatal adiposity.

BACKGROUND: The predisposition for obesity is suggested to originate in the prenatal period. Prenatal markers are needed to identify foetuses at risk for neonatal adiposity, as early marker of childhood obesity. OBJECTIVE: The aim of this study is to assess the association between foetal fractional thigh volume (TVol) and neonatal percentage fat mass from mid-gestation onward. METHODS: In this perinatal cohort study, singleton pregnancies with term born infants were included. Foetal TVol was measured on three-dimensional ultrasound scans (3D US) obtained at 22, 26 and 32 weeks of gestation. Neonatal body composition measurement (percentage body fat (%BF)) was planned between 42+0 and 42+6 -week postmenstrual age. Cross-sectional and longitudinal linear regression analyses were performed. RESULTS: Seventy-nine mother-child pairs were included. Median (interquartile range) TVol increased from 7.6 (7.1; 8.5) cm3 at 22 weeks to 36.5 (33.8; 40.9) cm3 at 32 weeks. Median neonatal %BF was 14.3% (11.7; 17.0). TVol at 22 weeks (ß = -1.58, 95% CI -2.45; -0.70, explained variance 31%) was negatively associated with %BF, but no associations were found at 26 and 32 weeks of gestation. TVol growth between 22 and 32 weeks of gestation (explained variance 18%) was also statistically significantly negatively associated with %BF. CONCLUSIONS: Foetal TVol is a promising 3D US marker for prediction of neonatal adiposity from mid-gestation onward.

New Ultrasound Measurements to Bridge the Gap between Prenatal and Neonatal Brain Growth Assessment.

BACKGROUND AND PURPOSE: Most ultrasound markers for monitoring brain growth can only be used in either the prenatal or the postnatal period. We investigated whether corpus callosum length and corpus callosum-fastigium length could be used as markers for both prenatal and postnatal brain growth. MATERIALS AND METHODS: A 3D ultrasound study embedded in the prospective Rotterdam Periconception Cohort was performed at 22, 26 and 32 weeks' gestational age in fetuses with fetal growth restriction, congenital heart defects, and controls. Postnatally, cranial ultrasound was performed at 42 weeks' postmenstrual age. First, reliability was evaluated. Second, associations between prenatal and postnatal corpus callosum and corpus callosum-fastigium length were investigated. Third, we created reference curves and compared corpus callosum and corpus callosum-fastigium length growth trajectories of controls with growth trajectories of fetuses with fetal growth retardation and congenital heart defects. RESULTS: We included 199 fetuses; 22 with fetal growth retardation, 20 with congenital heart defects, and 157 controls. Reliability of both measurements was excellent (intraclass correlation coefficient ≥ 0.97). Corpus callosum growth trajectories were significantly decreased in fetuses with fetal growth restriction and congenital heart defects (ß = -2.295; 95% CI, -3.320-1.270; P < .01; ß = -1.267; 95% CI, -0.972-0.562; P < .01, respectively) compared with growth trajectories of controls. Corpus callosum-fastigium growth trajectories were decreased in fetuses with fetal growth restriction (ß = -1.295; 95% CI, -2.595-0.003; P = .05). CONCLUSIONS: Corpus callosum and corpus callosum-fastigium length may serve as reliable markers for monitoring brain growth from the prenatal into the postnatal period. The clinical applicability of these markers was established by the significantly different corpus callosum and corpus callosum-fastigium growth trajectories in fetuses at risk for abnormal brain growth compared with those of controls.

[Domperidone to promote lactation]. / Domperidon ter bevordering van de lactatie.

- Breast milk is the best diet for all newborns, especially premature newborns.- In case of insufficient production of breast milk, feeding and extraction techniques should be optimized first, preferably supported by a lactation consultant. When supportive measures fail, domperidone to promote milk production can be considered.- The risk of side effects in newborns is negligible. The risk of maternal arrhythmias associated with QTc prolongation is low as long as domperidone is prescribed in low doses (10 mg tds).- In the absence of risk factors it is not necessary to routinely perform an ECG and, therefore, general practitioners can safely prescribe domperidone.- The effect of the treatment should be evaluated after 2 weeks. In case of prolonged treatment or use of higher dosages, it is recommended to perform an ECG to exclude QTc prolongation.

A New Ultrasound Marker for Bedside Monitoring of Preterm Brain Growth.

BACKGROUND AND PURPOSE: Preterm neonates are at risk for neurodevelopmental impairment, but reliable, bedside-available markers to monitor preterm brain growth during hospital stay are still lacking. The aim of this study was to assess the feasibility of corpus callosum-fastigium length as a new cranial sonography marker for monitoring of preterm brain growth. MATERIALS AND METHODS: In this longitudinal prospective cohort study, cranial ultrasound was planned on the day of birth, days 1, 2, 3, and 7 of life; and then weekly until discharge in preterm infants born before 29 weeks of gestational age. Reproducibility and associations between clinical variables and corpus callosum-fastigium growth trajectories were studied. RESULTS: A series of 1-8 cranial ultrasounds was performed in 140 infants (median gestational age at birth, 27(+2) weeks (interquartile range, 26(+1) to 28(+1); 57.9% male infants). Corpus callosum-fastigium measurements showed good-to-excellent agreement for inter- and intraobserver reproducibility (intraclass correlation coefficient >0.89). Growth charts for preterm infants between 24 and 32 weeks of gestation were developed. Male sex and birth weight SD score were positively associated with corpus callosum-fastigium growth rate. CONCLUSIONS: Corpus callosum-fastigium length measurement is a new reproducible marker applicable for bedside monitoring of preterm brain growth during neonatal intensive care stay.

Studies of pear-shaped nuclei using accelerated radioactive beams.

There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.

Evaluation of an in-house cat scratch disease IgM ELISA to detect Bartonella henselae in a routine laboratory setting.

Cat scratch disease (CSD) is caused by Bartonella henselae infection and is a common cause of regional lymphadenopathy. The diagnosis of CSD largely depends on serology, but detection of B. henselae in an affected lymph node by PCR is also an important diagnostic tool. We evaluated an IgM in-house ELISA protocol and analyzed its performance in routine CSD serology. Serum samples from PCR-positive patients (n = 126), PCR-negative patients (n = 123), and age-matched controls (n = 126) were used for evaluation. The sensitivity of the IgM ELISA was only 56%, showing that the performance of B. henselae serology under routine laboratory settings is low, probably caused by the wide variability in disease duration in patients suspected of CSD whose samples were submitted to our laboratory. Most patients (46%) with a positive IgM response were between 0 and 20 years of age. We conclude that the serodiagnosis of B. henselae is hampered by the low sensitivity and specificity of the assays when used in a routine laboratory setting. For this reason, a negative IgM or PCR result can never exclude CSD, especially with late sample collection.

The use of Bartonella henselae-specific age dependent IgG and IgM in diagnostic models to discriminate diseased from non-diseased in Cat Scratch Disease serology.

Cat Scratch Disease (CSD) is caused by Bartonella henselae infection and is a common cause of regional lymphadenopathy. The diagnosis of CSD largely depends on serology, but is hampered by both low sensitivity and specificity of the applied IgG and IgM assays. Using an in-house ELISA, we detected a significant age-dependent increase in the IgG levels in the general population compared to CSD patients. With this knowledge, we developed diagnostic models to differentiate diseased from non-diseased persons. Evaluation of these models using samples from PCR-positive patients (n=155) and age-matched controls (n=244) showed an important increase in the assay performance if the combination of the IgG and IgM results were taken into account. If the specificity was set at 98% the sensitivity was only 45% and 32% for the IgM and IgG ELISA, respectively but increased to 59% when these results were combined. Also the use of age-dependent factors further improved the clinical relevance of the outcome raising the sensitivity to 64%. Although the sensitivity of the ELISA remains low we conclude that the use of models using the combination of both IgM and IgG test results and age-depending factors can be a useful diagnostic tool in the serodiagnosis of CSD.

Evaluation of an internally controlled real-time polymerase chain reaction assay targeting the groEL gene for the detection of Bartonella spp. DNA in patients with suspected cat-scratch disease.

Bartonella (B.) henselae is the causative agent of cat-scratch disease (CSD), which usually presents as a self-limiting lymphadenopathy. This study reports the development and evaluation of an internally controlled real-time polymerase chain reaction targeting the groEL gene for detection of Bartonella spp. DNA was extracted using the MagNA Pure system. The lower detection limit was 10-100 fg DNA and the in vitro sensitivity of the assay was not affected by duplexing with an internal control PCR. The real-time PCR assay detected DNA from all five B. henselae strains tested, and from B. birtlesii, B. vinsonii subsp. vinsonii, B. vinsonii subsp. arupensis and B. doshiae. The assay generated negative results with a selection of other bacteria, including several Mycobacterium spp., Streptococcus pyogenes and Staphylococcus aureus. Results of real-time PCR in clinical samples were compared with those of a conventional 16S rDNA-based PCR assay. During the period described in the Material and methods section, real-time PCR and conventional 16S PCR were performed on 73 clinical samples. Of these samples, 29 (40%) were found to give positive results and 44 (60%) gave negative results, both by real-time PCR and by conventional PCR, with a 100% agreement between the two tests. The PCR developed in this study is a rapid, sensitive, and simple method for the detection of Bartonella spp. in CSD and is suitable for implementation in the diagnostic laboratory.

Serological testing for Bartonella henselae infections in The Netherlands: clinical evaluation of immunofluorescence assay and ELISA.

Cat-scratch disease (CSD), caused by Bartonella henselae infection, can mimic malignancy and can manifest atypically. Reliable serological testing is therefore of great clinical importance. The diagnostic performance of immunofluorescence assay (IFA) and ELISA was evaluated in a group of Dutch patients with proven CSD (clinical diagnosis confirmed by PCR). Sera of 51 CSD patients and 56 controls (patients with similar symptoms, but who were B. henselae PCR-negative and had an alternative confirmed diagnosis) were tested for anti-B. henselae IgM and IgG by IFA and ELISA. A commercially available IFA test for IgM had a sensitivity of 6%. In-house assays for IgM showed specificities of 93% (IFA) and 91% (ELISA), but with low sensitivities (53% and 65%, respectively). With a specificity of 82% (IFA) and 91% (ELISA), in-house IgG testing showed a significantly higher sensitivity in IFA (67%) than in ELISA (28%, p <0.01). Sensitivity was higher for genotype I (38-75%) than for genotype II (7-67%) infections, but this was only statistically significant for IgG ELISA (p <0.05). In conclusion, detection of IgM against B. henselae by in-house ELISA and IFA was highly specific for the diagnosis of CSD. The high seroprevalence in healthy individuals limits the clinical value of IgG detection for diagnosing CSD. Given the low sensitivity of the serological assays, negative serology does not rule out CSD and warrants further investigation, including PCR. Adding locally isolated (e.g., genotype II) B. henselae strains to future tests might improve the sensitivity.

Risk of congenital anomalies detected during antenatal serum screening in women with pregestational diabetes.

BACKGROUND: Most studies comparing women with and without pregestational diabetes mellitus have not systematically screened for fetal anomalies in early pregnancy, potentially leading to selection bias. AIM: To evaluate the risk for certain congenital anomalies in women participating in an antenatal maternal screening program. DESIGN: Retrospective cohort study. METHODS: We studied all women who underwent antenatal maternal serum screening in Ontario from 1994 to 2000. Fetal anomalies were documented antenatally by ultrasonography or at autopsy, and postnatally diagnosed birth defects were recorded after 20 weeks gestational age for all live- and stillborn affected infants. We compared the risk of open neural tube defects and urinary tract defects among women with and without pregestational diabetes. RESULTS: Of 413,219 women screened during pregnancy, 2069 (0.5%) had diabetes. Compared to non-diabetic women, the adjusted odds ratios (95%CI) for neural tube and urinary tract defects among women with diabetes were 2.5 (0.9-6.8) and 2.6 (1.4-4.9), respectively. DISCUSSION: Among women who undergo second trimester maternal serum screening, pregestational diabetes is associated with an increased risk of having a fetus with an open neural tube defect or urinary tract disorder.

Persistence of vitamin B12 insufficiency among elderly women after folic acid food fortification.

OBJECTIVE: To estimate the associated risk of folate and vitamin B12 (B12) insufficiency, as well as vitamin repletion, following folic acid food fortification. DESIGN: Retrospective cross-sectional study over a 5-year period. SETTING: Two large laboratory databases in the provinces of Ontario and British Columbia, Canada. PARTICIPANTS: Canadian women aged 65 years and over who underwent concomitant clinical testing of serum folate and B12 during the pre-fortification period of January 1996 to December 1997 in Ontario (n = 733) and British Columbia (n = 3839), and in the near-complete post-fortification period of January 1998 to December 2000 in Ontario (n = 4415) and British Columbia (n = 6677). MEASUREMENTS: Geometric mean concentrations of serum folate and B12 before and after folate fortification. Prevalence ratios (PR) were used to separately compare the post- and pre-fortification period rates of folate deficiency (below 6.0 nmol/L); B12 insufficiency (below 150 pmol/L); and B12 insufficiency in combination with supraphysiological concentrations of serum folate (above 45 nmol/L). RESULTS: The mean baseline folate and B12 concentrations were similar between provinces. Using the combined provincial data, the mean serum folate concentration increased by 64% after fortification, from 14.8 to 24.2 nmol/L (p < 0.001). The average B12 concentration increased from 280 to 300 pmol/L, which was more pronounced in BC (p < 0.001) than in Ontario (p = 0.16). The prevalence of folate deficiency declined from 6.3% to 0.88% after fortification (PR 0.14, 95% confidence interval [CI] 0.11-0.18), while the decline in B12 deficiency was less pronounced (PR 0.78, 95% CI 0.71-0.86). CONCLUSIONS: The prevalence of combined B12 insufficiency with supraphysiological concentrations of serum folate increased from 0.09% pre-fortification to 0.61% post (PR 7.0, 95% CI 2.6-19.2). The introduction of folic acid food fortification was associated with a substantial improvement in the folate status of Canadian women aged 65 years and older, paralleled by a large decline in the rate of folate deficiency. Improvement in the B12 status of these women was far less pronounced. Because the prevalence of combined B12 insufficiency and supraphysiological concentrations of serum folate may have increased with folic acid food fortification, consideration should be given to confirming this finding, and possibly, to the addition of B12 to folate fortified foods.

Declining rate of folate insufficiency among adults following increased folic acid food fortification in Canada.

OBJECTIVE: Canada introduced a mandatory folic acid food fortification program in November 1998. We investigated whether the rate of folate and vitamin B12 insufficiency among adults has changed since this mandatory fortification program was implemented. METHODS: We conducted a retrospective cross-sectional study using a large Ontario laboratory database. We included all individuals who underwent evaluation of their serum folate, red cell folate and serum vitamin B12 between April 1, 1997 to July 31, 1998 (Period A), August 1, 1998 to January 30, 1999 (Period B) and February 1, 1999 to March 31, 2000 (Period C). RESULTS: A total of 8,884 consecutive samples were analyzed during the period of study. Mean age was 57.4 years (SD 21.1), and 63.2% were female. The prevalence of serum folate insufficiency (below 3.4 nmol/L) fell from 0.52% in Period A to 0.22% in Period C [prevalence ratio (RR) 0.41, 95% confidence interval (CI) 0.18-0.93)]. The prevalence of red cell folate insufficiency (below 215 nmol/L) declined from 1.78% during Period A to 0.41% in Period C (RR 0.23, 95% CI 0.14-0.40). No significant difference was observed between periods in the prevalence of B12 insufficiency below 120 pmol/L (3.93% versus 3.11%, respectively; RR 0.79, 95% CI 0.62-1.01). CONCLUSIONS: There has been a significant decline in the prevalence of folate, but not vitamin B12 insufficiency, following Canadian folic acid food fortification. These changes may have important implications for the prevention and detection of folate and vitamin B12 insufficiency, including identifying the benefits of folic acid food fortification and the need to further consider fortification or supplementation with vitamin B12.

Platelet count may predict abnormal bleeding time among pregnant women with hypertension and preeclampsia.

BACKGROUND: Anesthesiologists often require laboratory data to estimate the bleeding risk among hypertensive pregnant women prior to administering regional anesthesia. Many rely on the bleeding time (BT) in making this determination. We examined whether the platelet count can adequately predict BT among a group of hypertensive parturients. METHODS: This retrospective subgroup analysis, taken from a cohort of 2,051 hypertensive pregnant women, comprises 87 individuals who underwent both a BT and platelet count prior to delivery. We calculated the correlation between the platelet count and BT at three platelet cut-off points with respect to prolonged BT of eight minutes or more. RESULTS: There was a significant negative correlation between platelet count at delivery and BT [r= -0.45, 95% confidence interval (CI) -0.26 to -0.60; P <0.0001]. All three platelet cut-off points had a sensitivity of less than 66% with negative predictive values below 75% for an abnormal BT. A platelet count > or =75 x 109/L [corrected] was specific for the presence of an abnormal BT (specificity 97.8%, 95% CI 91.7-100.0), with a positive predictive value of 95.5% (95% CI 83.1-100.0) and a positive likelihood ratio of 24 (95% CI 3.3-168). CONCLUSIONS: In a group of hypertensive parturients, the platelet count appears to be very specific for predicting a prolonged BT The platelet count may aid the anesthesiologist in determining the risk of bleeding from regional anesthesia. Given the study's potential for bias future research is needed to validate these findings.

MOS HIP: McMaster outcome study of hypertension in pregnancy.

BACKGROUND: The offspring of women with hypertension during pregnancy are at increased risk of low birthweight, preterm birth, diseases of prematurity and death. The risk of developing these outcomes among women with either preeclampsia or chronic hypertension, relative to those with gestational hypertension, is not known. STUDY DESIGN: Prospective cohort study. PARTICIPANTS: A total of 1948 singleton women seen at a large tertiary care obstetrical center, whose blood pressure was greater than 140/90 mm Hg during pregnancy. The four types of hypertension were strictly defined: 864 women (44.4%) had gestational hypertension, 459 (23.6%) isolated chronic hypertension, 501 (25.7%) isolated preeclampsia, and 124 (6.4%) chronic hypertension with superimposed preeclampsia. OUTCOME MEASURES: The primary outcome of the study was a composite of the diseases of prematurity, need for assisted ventilation for greater than 1 day, or perinatal death. The secondary outcomes were each of those included in the primary endpoint, as well as admission to the neonatal ICU, small for gestational age (SGA) birthweight and preterm birth. We controlled for the effects of other maternal risk factors, such as age, parity, history of preterm delivery, cigarette smoking, pre-pregnancy weight, diabetes mellitus (DM), renal dysfunction, and current use of an antihypertensive agent or prednisone. RESULTS: For the primary composite outcome, compared to the offspring of women with gestational hypertension, the adjusted odds ratio was 1.9 (95% confidence interval 1.2 to 3.0) in the preeclamptic group and 2.0 (95% confidence interval 1.0 to 4.0) for those with chronic hypertension plus superimposed preeclampsia. Those with preeclampsia were at increased risk for small for gestational age birthweight (odds ratio 2.2, 95% confidence interval 1.5 to 3.1), as were the offspring of mothers who had chronic hypertension with superimposed preeclampsia (odds ratio 2.1, 95% confidence interval 1.2 to 3.8). Similarly, the rate of preterm birth before 32 weeks was highest among the infants of both preeclamptic mothers (28.5%; odds ratio 4.7, 95% confidence interval 2.9 to 7.6) and those with chronic hypertension and preeclampsia (30.5%; odds ratio 3.5, 95% confidence interval 1.8 to 6.7). The perinatal mortality rate was highest in the group of women with chronic hypertension plus preeclampsia (9.2%; odds ratio 3.2, 95% confidence interval 1.2 to 9.1). Other significant risk factors for the primary composite outcome included previous preterm delivery (odds ratio 2.7, 95% confidence interval 1.4 to 5.2), smoking (odds ratio 1.8, 95% confidence interval 1.1 to 3.0) and use of an antihypertensive agent during pregnancy (odds ratio 1.8, 95% confidence interval 1.2 to 2.7). Prednisone use was strongly associated with risk for perinatal death (odds ratio 4.9, 95% confidence interval 1.4 to 17.1). CONCLUSIONS: Relative to women with isolated gestational hypertension, those who develop preeclampsia, either with or without underlying chronic hypertension, experience worse perinatal outcomes. A history of previous preterm delivery and maternal smoking increase the rate preterm birth and major perinatal disease. Antihypertensive and prednisone therapy may be important risk factors for adverse perinatal events, but further research is needed to confirm these findings.

Maternal and neonatal outcomes in pregestational and gestational diabetes mellitus, and the influence of maternal obesity and weight gain: the DEPOSIT study. Diabetes Endocrine Pregnancy Outcome Study in Toronto.

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.