Should we look for Hirschsprung disease in all children with meconium plug syndrome?

BACKGROUND: Meconium plug syndrome (MPS) is associated with Hirschsprung disease (HD) in 13-38% of cases. This study sought to assess institutional variation in utilization of rectal biopsy in children with MPS and the likelihood of diagnosing HD in this population. METHODS: Patients with MPS on contrast enema in the first 30 days of life from the Pediatric Health Information System database in 2016-2017 were included. Institutional rates of rectal biopsies performed during the initial admission were calculated and then used to predict institutional rates of early HD diagnoses using Poisson regression. RESULTS: Of 373 newborns with MPS, 106 (28.4%) underwent early rectal biopsy, of whom 43 (40.5%) had HD. Fifty-seven (15.3%) were ultimately diagnosed with HD. Eight (14%) of these patients had a delayed diagnosis. HD rates between institutions did not differ significantly (range 0-50%, p=0.52), but usage of early rectal biopsy did (range 0-80%, p=0.03). Each additional early biopsy increased the early HD diagnosis rate by 35% (ß=0.30, 95% CI 0.15-0.45, p<0.0001). CONCLUSION: The incidence of HD is increased in children with MPS. There is significant hospital variability in the utilization of early rectal biopsy, and opportunity exists to standardize practice. TYPE OF STUDY: Study of Diagnostic test Level of Evidence: Level III.

Is fetal pain a real evidence?

UNLABELLED: Due to the progress in fetal surgery, it is important to acquire data about fetal pain. MATERIAL AND METHODS: We performed a Medline research from 1995, matching the following key words: "pain" and "fetus", with the following: "subplate", "thalamocortical", "myelination", "analgesia", "anesthesia", "brain", "behavioral states", "substance p". We focused on: (a) fetal development of nociceptive pathways; (b) fetal electrophysiological, endocrinological and behavioral reactions to stimuli and pain. RESULTS: We retrieved 217 papers of which 157 were highly informative; some reported similar data or were only case-reports, and were not quoted. Most endocrinological, behavioral and electrophysiological studies of fetal pain are performed in the third trimester, and they seem to agree that the fetus in the 3rd trimester can experience pain. But the presence of fetal pain in the 2nd trimester is less evident. In favor of a 2nd trimester perception of pain is the early development of spino-thalamic pathways (approximately from the 20th week), and the connections of the thalamus with the subplate (approximately from the 23rd week). Against this possibility, some authors report the immaturity of the cortex with the consequent lack of awareness, and the almost continuous state of sleep of the fetus. CONCLUSIONS: Most studies disclose the possibility of fetal pain in the third trimester of gestation. This evidence becomes weaker before this date, though we cannot exclude its increasing presence since the beginning of the second half of the gestation.

Management of red cell alloimmunized pregnancies using conventional methods compared with that of middle cerebral artery peak systolic velocity.

The aim of this retrospective study was to find out the effect of change in the management of red cell alloimmunized pregnancies from conventional method of amniocentesis to the Doppler assessment of middle cerebral artery peak systolic velocity (MCA-PSV). There were 29 alloimmunized pregnancies affected by red cell antibodies. Ten cases were managed by amniocentesis and another 19 were managed by MCA-PSV measurements. The antenatal management and perinatal outcome of both groups are presented. This study suggests that the non-invasive monitoring should be the method of choice to monitor alloimmunized pregnancies.

Successful pregnancies on nocturnal home hemodialysis.

BACKGROUND AND OBJECTIVES: Women of childbearing age on conventional hemodialysis (CHD) have decreased fertility when compared with the general population. Even in women who conceived, maternal morbidity and fetal mortality remained elevated. We hypothesized that nocturnal hemodialysis (NHD) (3 to 6 sessions per week, 6 to 8 h per treatment), by augmenting uremic clearance, leads to a more hospitable maternal environment and therefore superior outcomes in fertility and pregnancy compared with CHD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This is a descriptive cohort study of all female patients achieving pregnancy and delivering a live infant while on NHD at the University Health Network, St. Michael's Hospital, and Humber River Regional Hospital from 2001 to 2006 in Toronto, Canada. Our primary objective was to describe maternal and fetal outcomes in addition to the changes in biochemical parameters after conception in our cohort. RESULTS: Our cohort included five patients (age range, 31 to 37 yr) who had seven pregnancies while on NHD and delivered six live infants. All had previously been on CHD, but none conceived during that time. In all patients, the amount of hemodialysis was increased (from a weekly mean of 36 +/- 10 to 48 +/- 5 h; P < 0.01) after pregnancy was diagnosed. Mean predialysis blood urea and mean arterial BP were maintained within normal physiological parameters. The mean gestational age of the cohort was 36.2 +/- 3 wk and the mean birth weight was 2417.5 +/- 657 g. The maternal and fetal complications observed in the cohort included intrauterine growth restriction or small for gestational age (n = 2), preterm delivery (<32 wk) (n = 1), and shortened cervix threatened labor (n = 1). Anemia was accentuated during pregnancy, and intravenous iron and erythropoietin requirements were increased. To maintain normal physiological indices for plasma phosphate, an augmented dialysate phosphate supplementation regimen was required. CONCLUSIONS: NHD may allow for improved fertility. Delivering a live infant at a mature gestational age is feasible for patients on NHD. Our cohort tended to have fewer maternal and fetal complications compared with historical controls. Hemoglobin and phosphate levels must be monitored with treatment adjusted accordingly.

Reassuring fetal middle cerebral artery doppler velocimetry in alloimmunised pregnancies: neonatal outcomes without invasive procedures.

OBJECTIVE: To assess the neonatal outcome in red blood cell alloimmunised pregnancies at increased risk of fetal anaemia where invasive testing was avoided based on reassuring middle cerebral artery (MCA) Doppler velocity results. METHODS: We included 28 alloimmunised pregnant women at significant risk of fetal or neonatal anaemia who did not have invasive testing because of reassuring MCA Doppler velocimetry. Women requiring invasive testing or intrauterine transfusion were excluded. Outcome measures were admission to neonatal intensive care unit, cord haemoglobin and bilirubin levels and neonatal therapy. RESULTS: Ten neonates (36%) were anaemic at birth while 18 (64%) had normal haemoglobin. Seven neonates (25%) did not require any form of neonatal therapy, 10 (36%) had phototherapy only, 7 (25%) required exchange transfusions and 4 (14%) top-up transfusions. There were no treatment-related complications. Mean cord haemoglobin was 13.9 g/dl (range 7-18.9) and mean bilirubin was 84.1 micromol/l (range 29-192). CONCLUSION: Avoiding invasive procedures in pregnancies at risk of fetal anaemia by relying on reassuring MCA Doppler velocimetry did not result in life-threatening fetal or neonatal morbidities. The extent of neonatal therapy was acceptable. The routine use of this test can lead to less unnecessary invasive procedures in at-risk fetuses.

[Reduction of HIV mother-to-child transmission in Colombia, two years of experience, 2003-2005]. / Reducción de la transmisión madre hijo del VIH en Colombia: dos años de experiencia nacional, 2003-2005.

INTRODUCTION: A national initiative on reduction of HIV mother-to-child-transmission is being implemented since 2003 in Colombia, including HIV counseled and voluntary testing as part of the routine antenatal care, comprehensive care with ARV treatment to HIV-positive pregnant women and their infected children, caesarian delivery, and replacement of breast milk. OBJECTIVE: To describe the achievements in the implementation of the prevention strategy of mother-to-child HIV transmission, 2003-2005. MATERIALS AND METHODS: The implementation procedures of the Project are described, as well as the coverage percentages achieved, the prevention of vertical transmission and its associated factors, and the six-month prevalence by geographical departments. The probability of transmission adjusted to the ARV treatment offered and the differences by regions are also analyzed. RESULTS: The Project was implemented in 757 municipalities (68%); diagnostic tests were performed to 200,853 pregnant women, 377 of whom were diagnosed as HIV positive (0.19%), with higher prevalences in the Caribbean region, and in the Departments of Quindio and Santander. Complete six-month follow-up after delivery was provided to 285 women and their neonates (12 of whom were HIV-positive). The probability of transmission with the use of ARV schemes during pregnancy (n=170) was 1.78% (IC 95%: 0.37-5.13%). Factors related to probability of transmission were: initial viral load > 10,000/mm3, absence of antenatal care, and late recruitment of pregnant women. No statistical differences were found between the ARV schemes used. In the Caribbean region, antenatal care was lower, and late recruitment of pregnant women was higher. CONCLUSIONS: Reduction of HIV mother-to-child-transmission is an effective preventive intervention, which also strengthens the quality of antenatal care services. Sustainability of this initiative, with nationwide coverage, must be a target for national and regional public health authorities, and for health care providers.

Prevalence of trisomy 21 following folic acid food fortification.

Polymorphisms of maternal genes responsible for normal folate metabolism may be associated with an increased risk of fetal trisomy 21. By January 1998, most of Canada's flour was being fortified with folic acid. We investigated whether the prevalence of antenatally and postnatally detected trisomy 21 changed before and after folic acid food fortification. A total of 218,977 women underwent second trimester maternal serum screening for trisomy 21 in the 48 months before fortification and 117,986 women were screened in the 29 months after fortification. There were 375 identified cases of trisomy 21 before fortification (1.71 per 1,000), compared to 201 cases thereafter (1.70 per 1,000) for a crude prevalence ratio (PR) of 0.99 (95% confidence interval [CI] 0.84-1.18). The associated risk of trisomy 21 did not change after adjustment for mean maternal age (adjusted PR 0.99 [95% CI 0.82-1.19]). Similarly, no significant decline in the monthly prevalence of trisomy 21 was observed using autoregressive integrated moving average time series analysis (P = 0.24). In conclusion, we failed to observe a decline in the occurrence of trisomy 21 following folic acid food fortification.

Risk of neural tube defects in the offspring of thalassaemia carriers in Hong Kong Chinese.

The risk of having an offspring with neural tube defect is negatively correlated with early pregnancy maternal folate levels. Thalassaemia carriers often have subnormal folate levels. We postulate that their offspring may be at increased risk of having neural tube defect. We retrospectively reviewed the records of 1961 Chinese women referred to a tertiary centre for prenatal diagnosis between January 1997 and August 1998. Women with a mean corpuscular volume greater than 80 fl were assumed not to be alpha-thalassaemia-1 or beta-thalassaemia heterozygotes. alpha- and beta-thalassaemia heterozygotes were diagnosed by haemoglobin studies. Of the 1961 women studied, pregnancy outcome was not available in 20 and thalassaemia screening was not available in 109 and these were excluded from the final analysis. Two-hundred-and-six women were alpha-thalassaemia-1 heterozygotes, 102 women were beta-thalassaemia heterozygotes and one woman had HbE disease. Three alpha-thalassaemia carriers and one beta-thalassaemia carrier had a pregnancy affected by anencephaly (odds=1:76). In the 1523 non-carriers, five pregnancies were affected by spina bifida (odds=1:304). The odds ratio (95 per cent confidence interval) for neural tube defects in the alpha- and beta-thalassaemia carriers was 3.99 (1.07 to 14.94; p<0.05, Chi-square test). Because of the small number of affected pregnancies studied, the finding needs to be substantiated by a larger series. If the increased risk is genuine, women need to be screened for thalassaemia before conception and the thalassaemia carriers should be given periconceptional folate supplement to reduce the occurrence of neural tube defects.

Multifactorial basis of the syndrome of diabetic embryopathy.

OBJECTIVE: The aim of the current paper is to explore the multifactorial basis of diabetes-induced embryopathy. METHOD: A review of the literature regarding congenital malformations was undertaken to elucidate new advances in our understanding of diabetic embryopathy. Data from both clinical and experimental studies were collected and analyzed. RESULTS: Numerous investigators have demonstrated that hyperglycemia and other metabolic fuels produce teratogenic effects during organogenesis. However, the exact mechanism(s) involved have not been completely elucidated. We and others have shown that aberrant metabolic fuels including hyperglycemia and hyperketonemia are teratogenic and that these effects occur via the yolk sac which appears to be the target site of injury. Other proposed etiologic factors include nutrient deficient states in membrane lipids such as arachidonic acid and myo-inositol as well as the generation of excess free oxygen radicals. This review highlights the multiple theories that have been proposed and summarizes the experimental and clinical data which support a multifactorial basis. CONCLUSIONS: Evidence suggests that although the teratogenic process in the diabetic pregnancy is multifactorial, it may operate via a common pathway. Prevention of malformations in offspring of diabetic rats is achieved by glycemic control during organogenesis. Similar results may be obtained in a hyperglycemic state, provided there is restoration of essential fatty acid/phospholipid deficiency state and normalization of excess free radicals which may be achieved through dietary supplementation of polyunsaturated fatty acids, myoinositol, or antioxidants. The latter approach offers great promise as an adjunct to periconceptional glycemic control and as a dietary prophylaxis against the syndrome of diabetic embryopathy.

Persistent pulmonary hypertension of the newborn and smoking and aspirin and nonsteroidal antiinflammatory drug consumption during pregnancy.

OBJECTIVE: Prenatal causation of persistent pulmonary hypertension of the newborn (PPHB) is suggested by a specific pattern of pulmonary vascular remodeling observed immediately after birth in some infants with fatal PPHN. The goal of this study was to determine whether PPHN is associated with fetal exposure to: (1) tobacco and marijuana smoking (ie, contributors to fetal hypoxemia), (2) consumption of aspirin and other nonsteroidal antiinflammatory drugs (ie, inhibitors of prostaglandin synthesis), and (3) cocaine use (ie, a contributor to vasospasm). DESIGN: Case-control interview study. SETTING: Two Harvard-affiliated newborn intensive care units. PARTICIPANTS: Mothers of case infants who had PPHN or who met criteria for the referent group. INTERVENTIONS: During July 1985 through April 1989, we interviewed mothers of 103 infants with PPHN and 298 control infants. Because of potential selection bias that might result from recruiting only inborn control infants even though two-thirds of cases were outborn, separate analyses compared the 103 total and 35 inborn infants with PPHN with the 298 inborn control infants. Multivariate analyses were used to adjust for potential confounding factors, including maternal education and Medicaid health insurance (ie, two markers of socioeconomic status), other antenatal factors found to be associated with PPHN (ie, maternal urinary tract infection and diabetes mellitus), and the infant's sex. MAIN OUTCOME MEASURES: Self-reported use or consumption of tobacco, marijuana, cocaine, aspirin, and other nonsteroidal antiinflammatory drugs during pregnancy. RESULTS: The adjusted odds ratios (and 95% confidence intervals) for maternal pregnancy exposures to the factors of principal interest among the total study population were: aspirin, 4.9 (1.6-15.3); and nonsteroidal antiinflammatory drugs, 6.2 (1.8-21.8); for the inborn group they were aspirin, 9.6 (2.4-39.0); and nonsteroidal antiinflammatory drugs, 17.5 (4.3-71.6). Although the association between tobacco smoking during pregnancy and PPHN was elevated in univariate analyses, with odds ratios (and 95% confidence intervals) of 2.0 (1.2-3.4) and 1.3 (0.6-3.3) for total and inborn populations, respectively, the relationship was not significant after adjustment for all other factors in the final logistic regression model. Acknowledged illicit drug use was too infrequent (3.2%) to evaluate. CONCLUSION: Maternal consumption of nonsteroidal antiinflammatory drugs and aspirin during pregnancy or the reasons these drugs were ingested seem to contribute to an increased risk of PPHN.

Should assessment of amniotic fluid volume form an integral part of antenatal fetal surveillance of high risk pregnancy?

This study was conducted to evaluate the role of the Amniotic Fluid Index (AFI), used along with nonstress cardiotocography (NST) and fetal acoustic stimulation test (FAST), when required, in prediction of adverse pregnancy outcome. Over a 3-year period 565 pregnant women had antepartum fetal surveillance due to various high risk pregnancy factors and delivered within 7 days of the test. Antepartum fetal surveillance included nonstress cardiotocography together with estimation of AFI. Need for induction of labour, presence of meconium at rupture of membranes, Caesarean section for fetal distress, Apgar score at 5 minutes, need for neonatal endotracheal intubation, admission to neonatal special care unit and perinatal death were the main outcome measures. Nonreactive nonstress tests and Caesarean sections for fetal distress were more common and neonatal outcome was significantly poorer in patients with AFI < 5 cm than in those with higher AFI values. Of the 4 perinatal deaths in the group with AFI < 5 cm, 3 had a reactive NST within 7 days of fetal death. It is concluded that pregnancy outcome is often poor in the presence of very low AFI and in these cases a reactive NST loses its usual reassuring value. It is suggested that AFI estimation should be included as an integral part of antepartum fetal surveillance of high risk pregnancies.

[Foal diseases and foal loss]. / Untersuchungen von Fohlenerkrankungen und Fohlenverlusten.

An investigation was carried out upon occurrence and course of infectious and non infectious diseases as well as the mortality in foals born and raised at the State Stud Marbach/Lauter between 1982 and 1991. The foals have been investigated from birth to weaning, they consisted of 177 Thoroughbred Arabians and 285 German Warmblood foals (total 462 foals). The diseases were divided into pre-, peri- and postnatal according to their known or assumed cause and onset. There was a preponderance of prenatal diseases (11.25%) whereas the perinatal rate was 1.30% and the postnatal rate of diseases was 8.66%. The rate of infectious diseases increased from the pre- to the postnatal period of life. A comparison between the two breeds showed that 9% of the Arabian foals suffered from infectious diseases whereas only 4.9% of the Warmblood foals were similarly affected. This is probably linked to the lower level of colostral immunoglobulins in the Arab herd, as previously shown by us. The measurement of mare colostral and foal serum IgG as well as the paramunisation of neonatal and weaned foals are important factors in the prevention of infectious diseases.

Prenatal diagnosis and fetal therapy.

The protective effect of folic acid supplementation has been demonstrated in patients at risk of neural tube defects by a large, randomized double-blind study. The feasibility of second-trimester screening for Down syndrome, based on the combination of maternal and biochemical markers on maternal blood, has also been verified in two large series from both the United Kingdom and the United States. These results represent major advances in the field of prenatal diagnosis, which, in the future, is likely to rely more and more on better selection by noninvasive testing of high-risk patients. The emphasis has moved away from very early invasive testing due to concerns related to the safety of both early chorionic villus sampling and amniocentesis. Evaluation of renal damage in fetuses with obstructive uropathy by analysis of urinary biochemistry may constitute the basis for more efficient selection of cases amenable to antenatal treatment. Twin-to-twin transfusion syndrome remains a challenge for the future.

A prospective, randomized evaluation of intrapartum amnioinfusion. Fetal acid-base status and cesarean delivery.

Pregnancies with decreased amniotic fluid volume are prediposed to umbilical cord compression and variable fetal heart rate declerations. Intrapartum amnioinfusion has been utilized in an effort to reduce cord compression. Previous studies suggested that amnioinfusion may improve the fetal metabolic state and reduce the incidence of cesarean delivery in selected patients. In this study the hypothesis was tested that intrapartum amnioinfusion will relieve cord compression in pregnancies complicated by oligohydramnios and will result in a reduced incidence of fetal intolerance to labor as well as improved fetal acid-base status at delivery. Thirty-five patients fulfilling the inclusion criteria were randomized to either the control (n = 16) or amnioinfusion treatment group (n = 19). Analysis of the data suggested that the two groups were similar for the perinatal parameters evaluated. No differences were observed in the umbilical artery blood gas analysis or incidence of cesarean section between the two groups. Intrapartum amnioinfusion does not appear to improve the perinatal outcome in pregnancies with oligohydramnios.

[Comparison of intensified traditional insulin therapy and micropump therapy in pregnant women with type 1 diabetes mellitus]. / Confronto fra terapia insulinica tradizionale ottimizzata e con microinfusore in gravide affette da diabete mellito di tipo I.

Ten pregnant women, affected by type I diabetes mellitus, observed for the first time during the II-III month of pregnancy, were examined. These patients were divided in two groups at random: group A underwent continuous subcutaneous insulin infusion with micropump CPI 9100 Lilly; group B underwent intensified insulin therapy with three daily doses of MC rapid insulin, two of which associated with MC intermediate insulin. All the patients were able to monitor their own blood glucose levels at home by means of reactive strips and reflectometer. In both the groups the mean glycemic values during fast and two hours after meals, and the eventual presence of urinary keton bodies and hypoglycemic crisis were evaluated during the course of pregnancy: these parameters turned out to be identical in the two groups. The increased need of insulin, the maternal body weight gain, the week and mode of delivery, the neonatal weight and the maternal and fetal complications also turned out to be identical in the two groups. To conclude, a good maternal metabolic control can be obtained either with the intensified conventional insulin therapy of with micropumps, if the patients, being properly instructed, are responsible for the monitoring of their own blood glucose levels at home.