Nipple/Areola Dimensions in Early Breastfeeding.

Background: Nipple dimensions may be an important factor in breastfeeding (BF) initiation success. Objective: To establish standards of nipple/areola dimensions in early BF and to determine whether maternal age, gestational age (GA), parity, cup size, previous BF experience, and early (<2 hours) BF affect nipple dimensions (assessed on the second day of BF). Design/Methods: A total of 205 consecutive BF women were enrolled. They were all Caucasians, and had uncomplicated pregnancies, labors, and vertex vaginal deliveries. Measurements (immediately before and after BF) of nipple length and diameter and of prefeeding areolas were by sliding calipers. Results: In average, there were no significant differences between right (R) and left (L) side dimensions, except for post-BF nipple length, and post-BF horizontal nipple diameter (significantly higher on the L side). Both R and L nipple length correlated positively with maternal age, gravidity, parity, number of previously breastfed infants, and cumulative number of BF months. Early (<2 hours) first BF did not correlate with increased nipple length. Pre-BF nipple length correlated significantly with post-BF nipple length on both sides. There were significant differences between pre- and post- BF values in terms of nipple length (longer length post-BF), but not in terms of nipple diameter. In stepwise regression analysis, where pre-BF nipple length was the dependent variable, and parity (or maternal age, or previous BF), early first BF, and GA were independent variables, parity, maternal age, gravidity, or previous BF experience were positively and significantly associated with nipple length (p < 0.001). The correlation maternal age-nipple length remained significant in primigravida mothers. Conclusions: This study provided a set of standards for nipple and areola dimensions on day 2 of BF in Caucasian women. The only areola/nipple dimension significantly affected by BF is the nipple length. Increasing parity, maternal age, or previous BF experience is significantly associated with increased nipple length.

The goniomaxillar length/goniomandibular length ratio in normal newborn infants: A clinical tool for defining chin position abnormalities.

Retrognathia (recessed chin) and prognathism (prominent chin) often present as signs of an underlying condition. Accurate clinical definitions are important. Yet their definitions were according to "clinical impression", or to seldom used X-ray criteria. We propose a statistical and anthropometric definition of retrognathia and prognathism based upon the ratio between the goniomaxillar length (distance between the gonion at the mandible angle and the subnasale and the goniomandibular length (distance between the mandible angle and the most anterior point of the bony chin). We assumed that an increase in the ratio indicates retrognathia and a decrease reflects prognathism. We conducted a prospective, observational, anthropometric study in 204 consecutive healthy term infants. Measurements took place on the second day of life, using sliding calipers. Mean ± SD of goniomandibular length (5.1 ± 0.3 cm), goniomaxillar length (5.4 ± 0.3 cm), were calculated. All measurements correlated significantly with gestational age, and with infant birthweight. The mean ± SD goniomaxillar length/goniomandibular length ratio was 1.06 ± 0.05. We defined a normal ratio as being within 2 SD of the mean, that is, between 0.96 and and 1.16. This ratio correlated with neither gestational age nor with birthweight. We conclude that the goniomaxillar length/goniomandibular length ratio can be calculated whenever retro - or prognathism is suspected. A ratio outside of the 95% confidence interval should help in making this diagnosis. An increase in this ratio beyond 2 SD above the mean (1.16) could be interpreted as retrognathia and a decrease beyond 2 SD below the mean (0.96) as prognathism.

Green Breast Milk Following Ingestion of Blue-Green Algae: A Case Report.

Breast milk is an excellent nutritional source for newborns, and a change in its color can be alarming to both mother and physician, and may prevent breastfeeding. Different colors of breast milk have been reported such as blood-stained, blue, and bluish-green. We present the first case of green breast milk caused by maternal ingestion of blue-green algae pills immediately before and after delivery. The score on the Naranjo Adverse Drug Reaction Probability Scale was 5, indicating a probable adverse drug reaction. Laboratory analysis yielded no other abnormalities in the milk. The mother stopped taking the supplement, and the milk returned to its normal appearance 3 days later. This report should alert physicians to include supplement intake as part of the anamnesis for new mothers who present with breast milk changes.

For Debate: Does Cannabis Use by the Pregnant Mother Affect the Fetus and Newborn?

Cannabis, commonly called marijuana, is often used during pregnancy, likely due to the perception that it is a "safe" drug. Changes in legislation in many countries have lead to the increased availability of this drug and to its increasing use during pregnancy, often with other concomitant exposures such as alcohol, tobacco, and other drugs. Herein, we review the medical literature regarding effects of marijuana on the fetus and newborn. Possible effects of in utero exposure to marijuana focus on fetal growth, increase in the rates of stillbirth and preterm delivery, congenital malformations, and neurodevelopmental effects on the child. Published studies for all these outcomes are inconsistent. Fetal weight growth may be somewhat decreased, but the magnitude of this decrease is no greater than 100 g. There is insufficient evidence to conclude on any effect on the stillbirth rate. Although there are some reports of a slight increase in the rate of prematurity, most reports do not support this effect. Marijuana does not appear to be a major teratogen; however, a small increased risk for some congenital birth defects may be associated with early pregnancy use. Neurodevelopmental effects have been associated with marijuana use, but it is difficult to control for the effect of confounders. Despite the lack of conclusive evidence, it is important to remember that marijuana has not been shown to be a harmless drug during pregnancy and may affect the long-term neurodevelopment of the newborn infant.

Outcome of breastfed infants following post-partum methylergonovine treatment.

OBJECTIVE: To evaluate maternal and breastfed infant's outcome following post-partum maternal use of methylergonovine. METHODS: A prospective, controlled observational study design was used. Mothers who contacted Beilinson Teratology Information Service (BELTIS) were followed by phone interview. Data on lactation, neonatal symptoms and outcomes at the age of 1-3 years were obtained. Mothers' breastfeeding while treated with methylergonovine and their infants were compared to a matched control group of breastfeeding mothers using a drug known to be safe during lactation (amoxicillin). RESULTS: Follow-up was obtained for 38 of 42 women (90.5%). Of whom, six stopped breastfeeding because of concerns regarding drug treatment and three refused to participate. The remaining 29 women and infant pairs were compared to a control group of 58 women and their infants. Comparison showed no effect of methylergonovine on lactation and similarly showed no difference in rate of neonatal complications (p = 1). At time of follow-up there were no differences in growth or in adverse neurodevelopment outcomes (p = 0.26). CONCLUSIONS: No increase in adverse long-term outcomes was found in infants exposed to methylergonovine through breastfeeding. Our data in conjunction with previous estimates of very low drug exposure support continuation of breastfeeding in women requiring treatment with methylergonovine.

Pregnancy outcome following maternal exposure to pregabalin may call for concern.

OBJECTIVE: To investigate pregnancy outcomes following maternal use of pregabalin. METHODS: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs). Teratology Information Services systematically collected data between 2004 and 2013. RESULTS: Data were collected from 164 exposed pregnancies and 656 controls. A significantly higher major birth defect rate in the pregabalin group was observed after exclusion of chromosomal aberration syndromes, and when cases with exposure during first trimester of pregnancy were analyzed separately (7/116 [6.0%] vs 12/580 [2.1%]; odds ratio 3.0, 95% confidence interval 1.2-7.9, p = 0.03). The rate of live births was lower in the pregabalin group (71.9% vs 85.2%, p < 0.001), primarily due to a higher rate of both elective (9.8% vs 5.0%, p = 0.02) and medically indicated (5.5% vs 1.8%, p = 0.008) pregnancy terminations. In the Cox proportional cause specific hazards model, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion. CONCLUSIONS: This study demonstrated a signal for increased risk of major birth defects after first trimester exposure to pregabalin. However, several limitations such as the small sample size, differences across groups in maternal conditions, and concomitant medication exposure exclude definitive conclusions, so these results call for confirmation through independent studies.

Pregnancy outcome following maternal exposure to mirtazapine: a multicenter, prospective study.

This multicenter, observational prospective cohort study addresses the risk associated with exposure to mirtazapine during pregnancy. Pregnancy outcomes after exposure to mirtazapine were compared with 2 matched control groups: (1) exposure to any selective serotonin reuptake inhibitor (SSRI, control subjects with a psychiatric condition) and (2) no exposure to medication known to be teratogenic or any antidepressant (general control subjects). Data were collected by members of the European Network of Teratology Information Services between 1995 and 2011. Observations from 357 exposed pregnancies were compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; odds ratio [OR], 1.1; 95% confidence interval [95% CI], 0.5-2.3; P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general control subjects (4.5% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08) reached statistical significance after exclusion of chromosomal or genetic anomalies (4.1% vs 1.3%; OR, 3.3; 95% CI, 1.04-10.3; P = 0.03), but this difference became again nonsignificant if cases of exposure not comprising the first trimester were excluded from the analysis (3.4% vs 1.9%; OR, 1.8; 95% CI, 0.6-5.0; P = 0.26). The crude miscarriage rate did not differ significantly between the mirtazapine, the SSRI, and the general control groups (12.1% vs 12.0% vs 9.3%; P = 0.44). However, a higher rate of elective pregnancy termination was observed in the mirtazapine group compared with SSRI and general control subjects (7.8% vs 3.4% vs 5.6%; P = 0.03). This study did not observe a statistically significant difference in the rate of major birth defects after first-trimester exposure between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A marginally higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general control subjects. Overall pregnancy outcome after mirtazapine exposure was similar to that of the SSRI-exposed control group.

Colchicine use during breastfeeding.

OBJECTIVE: This study evaluated the outcome of infants exposed to colchicine during lactation. SUBJECTS AND METHODS: A prospective observational cohort study design was used. Mothers who contacted Beilinson Teratology Information Service (BELTIS) regarding use of colchicine while breastfeeding were followed up by phone interview. Data on lactation, neonatal symptoms, and outcome 1-3 years after initial consultation were obtained. Mothers breastfeeding while taking colchicine (n=37) and their infants (n=38) were compared with a matched control group of mothers using a drug known to be safe during lactation (n=75) and their infants (n=76). RESULTS: Follow-up was obtained for 59 of 76 (78%) women who contacted BELTIS regarding use of colchicine. Of the 59 women, 37 breastfed while taking colchicine, five did not take colchicine, 16 did not breastfeed, and one declined to participate. The mean duration of breastfeeding was similar in both groups. Adverse neonatal symptoms were seen in three of 38 colchicine-exposed infants versus four of 76 of control group infants (p=0.68). Delayed development or neurological abnormalities were seen in two infants in both study groups (p=0.60). None of the colchicine-exposed infants showed abnormal growth. CONCLUSIONS: No increase in adverse long-term outcomes was found in colchicine-exposed breastfed infants. Our data support continuation of breastfeeding in women treated with colchicine.

Outcome following tranexamic acid exposure during breastfeeding.

OBJECTIVE: This study evaluated the outcome of infants exposed to tranexamic acid during lactation. SUBJECTS AND METHODS: A prospective, controlled observational study design was used. Mothers who contacted the Beilinson Teratology Information Service (BELTIS) regarding use of tranexamic acid while breastfeeding were followed up by phone interview. Data on lactation, neonatal symptoms, and outcomes at the age of 1-3 years were obtained. Mothers' breastfeeding while taking tranexamic acid and their infants were compared with those of a matched control group of breastfeeding mothers using a drug known to be safe during lactation (amoxicillin) and their infants. RESULTS: Follow-up was obtained for 28 of 32 women who sought advice regarding use of tranexamic acid during breastfeeding. Of the 28 women, six did not take the drug, and one refused to participate. The 21 remaining women (study group) were compared with 42 control women. A decreased amount of breastmilk was reported by one woman in the study group versus two women in the control group (p=1.0). Possible adverse drug effects were reported for one of 21 study group infants (restlessness) and for one of 42 control group infants (gastroesophageal reflux) (p=1.0). Growth below the 3rd percentile was found in one of 21 study group infants versus four of 42 control group infants (p=0.66). Development was normal for all study group infants. CONCLUSIONS: No increase in adverse long-term outcomes was found in infants exposed through breastfeeding to tranexamic acid. Our data in conjunction with previous estimates of very low drug exposure support continuation of breastfeeding in women requiring treatment with tranexamic acid.

A novel technique for infant length measurement based on stereoscopic vision.

BACKGROUND: Monitoring infant growth is essential for evaluation of development and is an important indicator of health and illness. Length is an essential indicator of infant growth, however, length measurement methods suffer from limitations which restrict their use. OBJECTIVE: To improve infant length measurement by development of a novel, accurate, precise and practical measurement technique. METHODS: A new system based on stereoscopic vision was developed. The system is comprised of two digital still cameras combined with software that calculates the infant's length from two simultaneously taken pictures. Length measurements of 54 healthy newborns were performed using a standard length board and the stereoscopic system. The two measurement methods were compared. RESULTS: Mean infant length was 473.1 (SD=29.1) mm versus 473.3 (SD=29.3) mm by length board and by the stereoscopic system, respectively. The mean difference between measurements was 0.2 (SD=2.5) mm and the mean of the absolute values of differences was 2.0 (SD=1.4) mm. Bland-Altman analysis showed good agreement between the two measurement methods. Precision of the new technique was demonstrated by a technical error of measurement of 2.57 mm. CONCLUSIONS: The stereoscopic system is accurate, reliable, easy to use, and involves less handling and discomfort to the newborns. It has the potential to measure premature infants or sick neonates through incubators.

Antipsychotic drugs and breastfeeding.

OBJECTIVE: The incidence of psychotic disorders during the postpartum period is higher than at any other time during a women's life and coincides with the time when breastfeeding is most recommended. As a result, safety data on use of antipsychotic drugs during lactation is essential. Our aim was to analyze the medical literature for information on antipsychotic drug use during breastfeeding and to determine the safety of their use for the exposed infant. DATA SOURCES: Medline (U.S. National Library of Medicine), LactMed (U.S. National Library of Medicine) and Reprotox (Reproductive Toxicology Center) databases were searched to identify all relevant medical literature on antipsychotic medications and lactation. The database search, updated to March, 2012, used the generic name of each antipsychotic drug in combination with the terms breastfeeding or lactation or breast-milk. STUDY SELECTION: 4 prospective studies, 12 case series, 28 case reports and 1 pharmaceutical registry were included. DATA EXTRACTION: Infant outcomes focusing on long-term outcome were summarized from all reports of breastfeeding mothers taking antipsychotic medications. Recommendations for drug use during breastfeeding were based on safety data and on pharmaco kinetic drug properties. Recommendatins were categorized as acceptable, possible under medical supervision, or, not recommended. RESULTS: Among 21 antipsychotic drugs used in clinical practice, for 7 there are no data at all regarding breastfeeding and for 6 others the data are based only on few infant exposures. Only few prospective studies assessing'use of haloperidol, chlorpromazine and olanzapine during breastfeeding were identified. Olanzapine and quetiapine were categorized as acceptable for breastfeeding. Chlorpromazine, haloperidol, risperidone and zuclopenthixol were categorized as possible for breastfeeding under medical supervision. Breastfeeding cannot be currently recommended for the following medications: aripiprazole, asenapine, chlorprothixene, clozapine, droperidol, fluphenazine, flupenthixol, iloperidone, lurasidone, paliperidone, perphenazine, pimozide, trifluoperazine, thiothixene and ziprasidone. CONCLUSIONS: With a limited number of infants exposed to antipsychotic drugs during breastfeeding, for most drugs a firm and evidence-based conclusion cannot be reached. Counseling of breastfeeding mothers should be carefully assessed. Pharmacokinetic drug characteristics, disease severity, behavioral or psychosocial alternatives, preventative interventions and possible impact of discontinuing breastfeeding on the maternal-infant relationship should all be considered.

In utero oxcarbazepine and a withdrawal syndrome, anomalies, and hyponatremia.

Oxcarbazepine is an antiepileptic agent that has been used during pregnancy, although its safety during pregnancy has not been sufficiently established. This article presents an infant born with renal and cardiac malformations who developed a withdrawal syndrome and hyponatremia following in utero exposure to oxcarbazepine. The infant was born at 35 weeks' gestation by urgent cesarean section to a mother in status epilepticus who had been treated with oxcarbazepine throughout her pregnancy. Evaluation for congenital anomalies identified mild aortic stenosis, a bicuspid aortic valve, patent foramen ovale, patent ductus arteriosus, and severe left hydronephrosis due to left ureteropelvic junction stenosis. On the third day of life the infant developed clinical signs of a withdrawal syndrome, which peaked on day 7 and resolved by day 12. Transient hyponatremia resolved by day 8 of life. Follow-up showed normal development at 15 months. The association of a withdrawal syndrome with oxcarbazepine exposure has not been previously reported. The hyponatremia is consistent with adult reports. The possible association of oxcarbazepine with renal and cardiac malformations requires further confirmation.

Birth trauma--risk factors and short-term neonatal outcome.

OBJECTIVE: The ability to predict birth trauma (BT) based on the currently recognized risk factors is limited and there is little information regarding the short-term neonatal outcome following BT. We aimed to identify risk factors for BT and to evaluate the effect of BT on short-term neonatal outcome. METHODS: A retrospective, cohort, case-control study of all cases of BT in a single tertiary center (1986-2009). The control group included the two subsequent full-term singleton neonates who did not experienced BT. Short-term neonatal outcome was compared between the groups including Apgar scores, NICU admission, duration of hospitalization and neurologic, respiratory and metabolic morbidity. RESULTS: Of the 118 280 singleton full-term newborns delivered during the study period, 2874 were diagnosed with BT (24.3/1000). The most frequent types of BT were scalp injuries (63.9%, 15.5/1000) and clavicular fracture (32.1%, 7.7/1000). The following factors were found to be independent risk factors for BT: instrumental delivery (OR 7.5, 95% CI 6.3-8.9), birth weight, delivery during risk hours, parity, maternal age and neonatal head circumference. Cesarean delivery was the only factor protective of BT (OR 0.2, 95% CI 0.2-0.3). Neonates in the study group had a prolonged length of hospital stay (3.3 versus 2.7 d, p = 0.001), were more likely to be admitted to the NICU (3.9% versus 1.9%, p < 0.001), and had a higher rate of jaundice (11.9% versus 7.1%, p < 0.001) and neurological morbidity (4.7% versus 2.3%, p < 0.001). CONCLUSION: Instrumental delivery appears to be responsible for most cases of neonatal BT.

Evaluation of the efficacy and safety of bi-daily combination therapy with pyridoxine and doxylamine for nausea and vomiting of pregnancy.

BACKGROUND: Diclectin (pyridoxine 10 mg and doxylamine 10 mg) has traditionally been used to treat nausea and vomiting of pregnancy (NVP); however, this drug is unavailable in many countries. OBJECTIVES: To evaluate the efficacy and safety of a simple bi-daily treatment regimen with the combination of pyridoxine (50 mg twice daily) and doxylamine (25-50 mg) as an alternative treatment for NVP. METHODS: A prospective case-controlled observational study of mother-infant pairs was conducted between February 2008 and December 2010. All women who contacted the Beilinson Teratology Information Service (BELTIS) regarding treatment of NVP were eligible for inclusion. Using data on NVP severity, treatment efficacy and outcomes, we compared the two groups of women: those treated with the combination of pyridoxine and doxylamine (treatment group, n=29) and those treated with metoclopramide (control group, n=29). RESULTS: Moderate to severe symptoms were present in 97% of the treatment group women vs. 69% of control group women (P < 0.01). Despite increased symptom severity in the treatment group, the combination regimen was efficacious: 20/29 (69%) vs. 18/25 (72%) in the treatment vs. control women respectively (P = 0.65). There were no congenital anomalies in the treatment group. Follow-up was normal for all infants. CONCLUSIONS: Bi-daily combination therapy with pyridoxine and doxylamine for NVP is safe, has comparable efficacy to metoclopramide, and is a treatment alternative in countries where Diclectin is not available. Despite symptoms warranting counseling by a teratology information service, more than a third of women do not take the suggested treatment.

Levonorgestrel used for emergency contraception during lactation-a prospective observational cohort study on maternal and infant safety.

OBJECTIVE: To identify possible effects of levonorgestrel used as an emergency contraceptive during breastfeeding on mothers and their infants. STUDY DESIGN: A prospective observational cohort study of all women who contacted the Teratology Information Service between January, 2005 and January, 2010. Breastfeeding women who used levonorgestrel as an emergency contraceptive (study group) were compared to breastfeeding women who used either ethynodiol diacetate or desogestrel (control group). Women were followed for 6-24 months. Main outcome measures were adverse maternal and infant effects and continuation of breastfeeding. RESULTS: We followed 71 of 128 study group women and 72 of 100 control group women. Maternal adverse effects were mainly vaginal bleeding, which was less frequent in the study vs. control group (16 of 71 vs. 27 of 72, p = 0.068). Decreased lactation was uncommon and similar in both groups. Breastfeeding was reinitiated within less than 8 h in 75% of the levonorgestrel group women. Adverse infant effects were rare (0 of 72 infants vs. 2 of 72 infants, p = 0.5 in the study vs. control group). CONCLUSIONS: Our findings support the safety of using levonorgestrel as an emergency contraceptive during lactation without the need for withholding breastfeeding.

Prevalence of esophageal atresia among 18 international birth defects surveillance programs.

BACKGROUND: The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA. METHODS: The study population comprised infants diagnosed with EA during 1998 to 2007 from 18 of the 46 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research. Total prevalence per 10,000 births for EA was defined as the total number of cases in live births, stillbirths, and elective termination of pregnancy for fetal anomaly (ETOPFA) divided by the total number of all births in the population. RESULTS: Among the participating programs, a total of 2943 cases of EA were diagnosed with an average prevalence of 2.44 (95% confidence interval [CI], 2.35-2.53) per 10,000 births, ranging between 1.77 and 3.68 per 10,000 births. Of all infants diagnosed with EA, 2761 (93.8%) were live births, 82 (2.8%) stillbirths, 89 (3.0%) ETOPFA, and 11 (0.4%) had unknown outcomes. The majority of cases (2020, 68.6%), had a reported EA with fistula, 749 (25.5%) were without fistula, and 174 (5.9%) were registered with an unspecified code. CONCLUSIONS: On average, EA affected 1 in 4099 births (95% CI, 1 in 3954-4251 births) with prevalence varying across different geographical settings, but relatively consistent over time and comparable between surveillance programs. Findings suggest that differences in the prevalence observed among programs are likely to be attributable to variability in population ethnic compositions or issues in reporting or registration procedures of EA, rather than a real risk occurrence difference. Birth Defects Research (Part A), 2012.

The outcomes of pregnancy in women exposed to the new macrolides in the first trimester: a prospective, multicentre, observational study.

BACKGROUND: Macrolides are a group of commonly prescribed antibiotics. There is some doubt surrounding the use of the newer macrolides in pregnancy. OBJECTIVE: The present study aimed to compare outcomes of pregnancies exposed to the new macrolides clarithromycin, azithromycin and roxithromycin with non-teratogenic preparations. METHODS: In this prospective, multinational, multicentre, controlled, observational study, information was obtained either from pregnant women or their healthcare professionals who contacted their local teratogen information services in Italy, Israel, the Czech Republic, the Netherlands and Germany seeking information after exposure to macrolides. The comparison group included women or their healthcare professional who contacted these centres with questions regarding known non-teratogenic preparations. Information on obstetric and other background parameters was collected at enrollment; after delivery, subjects or their healthcare professionals were contacted to ascertain pregnancy outcome parameters and other exposures through the remainder of the pregnancy. RESULTS: A total of 608 women exposed to macrolides during pregnancy were enrolled; 511 of the exposures occurred during the first trimester. The comparison group comprised 773 women exposed to non-teratogenic preparations during the first trimester of pregnancy. No significant difference in the rate of major congenital malformations was found between the study group and the comparison group (3.4% vs 2.4%; p = 0.36; odds ratio (OR) 1.42; 95% CI 0.70, 2.88) or in the rate of cardiovascular malformations (1.6% vs 0.9%; p = 0.265; OR 1.91; 95% CI 0.63, 5.62). No significant differences were found between subgroups of macrolides in the rates of major congenital malformations or cardiac malformations, although for azithromycin this was of borderline significance. CONCLUSIONS: This study, in agreement with earlier smaller studies, suggests that the new macrolides do not pose a significantly increased risk of major congenital malformations or cardiac malformations.

New syndrome of congenital circumferential skin folds associated with multiple congenital anomalies.

Congenital circumferential skin folds can be found in individuals with no additional defects, as well as in patients with multiple congenital anomalies and developmental abnormalities. Current data point to etiological heterogeneity of syndromic cases. We describe a 7-month-old girl with a novel combination of symmetrical congenital circumferential skin folds, dysmorphic features, and multiple congenital abnormalities. Examination of the patient revealed symmetrical congenital circumferential skin folds and dysmorphic features, as well as multiple congenital anomalies including nasal pyriform aperture stenosis, ventricular septal defect, absent spleen, camptodactyly, and severe psychomotor retardation. Skin biopsy demonstrated subcutaneous fat extending into the superficial and deep reticular dermis. Sequencing of the CDON, SHH, ZIC2, SIX3, and TGIF genes (associated with holoprosencephaly) did not disclose pathogenic alterations. Extensive review of previously described cases of syndromic congenital circumferential skin folds did not reveal a similar combination of clinical and histopathological findings.