Decreased neonatal morbidity in 'stomach-down' left congenital diaphragmatic hernia: implications of prenatal ultrasound diagnosis for counseling and postnatal management.

OBJECTIVE: To evaluate the influence of stomach position on postnatal outcome in cases of left congenital diaphragmatic hernia (CDH) without liver herniation, diagnosed and characterized on prenatal ultrasound (US), by comparing those with ('stomach-up' CDH) to those without ('stomach-down' CDH) intrathoracic stomach herniation. METHODS: Infants with left CDH who underwent prenatal US and postnatal repair at our institution between January 2008 and March 2017 were eligible for inclusion in this retrospective study. Detailed prenatal US examinations, fetal magnetic resonance imaging (MRI) studies, operative reports and medical records of infants enrolled in the pulmonary hypoplasia program at our institution were reviewed. Cases with liver herniation and those with an additional anomaly were excluded. Cases in which bowel loops were identified within the fetal chest on US while the stomach was intra-abdominal were categorized as having stomach-down CDH. Cases in which bowel loops and the stomach were visualized within the fetal chest on US were categorized as having stomach-up CDH. Prenatal imaging findings and postnatal outcomes were compared between the two groups. RESULTS: In total, 152 patients with left CDH were initially eligible for inclusion. Seventy-eight patients had surgically confirmed liver herniation and were excluded. Of the 74 included CDH cases without liver herniation, 28 (37.8%) had stomach-down CDH and 46 (62.2%) had stomach-up CDH. Of the 28 stomach-down CDH cases, 10 (35.7%) were referred for a suspected lung lesion. Sixty-eight (91.9%) cases had postnatal outcome data available for analysis. There was no significant difference in median observed-to-expected (o/e) lung-area-to-head-circumference ratio (LHR) between cases with stomach-down CDH and those with stomach-up CDH (41.5% vs 38.4%; P = 0.41). Furthermore, there was no difference in median MRI o/e total lung volume (TLV) between the two groups (49.5% vs 44.0%; P = 0.22). Compared with stomach-up CDH patients, stomach-down CDH patients demonstrated lower median duration of intubation (18 days vs 9.5 days; P < 0.01), median duration of extracorporeal membrane oxygenation (495 h vs 223.5 h; P < 0.05), rate of supplemental oxygen requirement at 30 days of age (20/42 (47.6%) vs 3/26 (11.5%); P < 0.01) and rate of pulmonary hypertension at initial postnatal echocardiography (28/42 (66.7%) vs 9/26 (34.6%); P = 0.01). No neonatal death occurred in stomach-down CDH patients and one neonatal death was seen in a patient with intrathoracic stomach herniation. CONCLUSIONS: In infants with left CDH without liver herniation, despite similar o/e-LHR and o/e-TLV, those with stomach-down CDH have decreased neonatal morbidity compared to those with stomach herniation. Progressive or variable physiological distension of the stomach over the course of gestation may explain these findings. Stomach-down left CDH is mistaken for a lung mass in a substantial proportion of cases. Accurate prenatal US characterization of CDH is crucial for appropriate prenatal counseling and patient management. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

COVID-19 and developmental origins of health and disease.

From the moment of the identification of SARS-CoV-2 as an etiological agent of the severe clinical pictures of pneumonia that were being slowly observed all over the world, numerous studies have been conducted to increase the knowledge about what was an unknown virus until then. The efforts were mainly aimed to acquire epidemiological, microbiological, pathogenetic, clinical, diagnostic, therapeutic and preventive information in order to increase the available weapons to fight an infection which was rapidly taking on the characteristics of the pandemic. Given the topicality of the problem, not everything has yet been fully understood and clarified, especially in the maternal-fetal­neonatal field, where we are beginning to question what could be the outcomes of newborn babies born to mothers who contracted SARS-CoV-2 infection during pregnancy. Thus, the aim of this review is to analyze the long-term outcomes of this infection that could affect the offspring, regardless of a possible maternal-fetal transmission, focusing on, above all, the role of maternal immune activation and the expression of the Angiotensin-converting enzyme 2 (ACE2) in particular at the placental level.

YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress.

Neonatal diabetes is caused by single gene mutations reducing pancreatic ß cell number or impairing ß cell function. Understanding the genetic basis of rare diabetes subtypes highlights fundamental biological processes in ß cells. We identified 6 patients from 5 families with homozygous mutations in the YIPF5 gene, which is involved in trafficking between the endoplasmic reticulum (ER) and the Golgi. All patients had neonatal/early-onset diabetes, severe microcephaly, and epilepsy. YIPF5 is expressed during human brain development, in adult brain and pancreatic islets. We used 3 human ß cell models (YIPF5 silencing in EndoC-ßH1 cells, YIPF5 knockout and mutation knockin in embryonic stem cells, and patient-derived induced pluripotent stem cells) to investigate the mechanism through which YIPF5 loss of function affects ß cells. Loss of YIPF5 function in stem cell-derived islet cells resulted in proinsulin retention in the ER, marked ER stress, and ß cell failure. Partial YIPF5 silencing in EndoC-ßH1 cells and a patient mutation in stem cells increased the ß cell sensitivity to ER stress-induced apoptosis. We report recessive YIPF5 mutations as the genetic cause of a congenital syndrome of microcephaly, epilepsy, and neonatal/early-onset diabetes, highlighting a critical role of YIPF5 in ß cells and neurons. We believe this is the first report of mutations disrupting the ER-to-Golgi trafficking, resulting in diabetes.

An evaluation of fetal heart rate characteristics associated with neonatal encephalopathy: a case-control study.

OBJECTIVE: We sought to identify fetal heart rate (FHR) characteristics that are associated with neonatal encephalopathy (NE). DESIGN: Retrospective case-control study. SETTING: A single medical centre in Shanghai, China, 2006-2015. SAMPLE: Women delivering a singleton, non-anomalous infant at ≥36 weeks' gestation diagnosed with NE (cases, n = 109) were compared with a group of women with unaffected infants (controls, n = 233). METHODS: Two physicians blinded to the outcome independently reviewed FHR tracings during the last 30 minutes of tracing prior to delivery. FHR characteristics were compared in the two groups and multivariable logistic regression was used to adjust for confounding. MAIN OUTCOME MEASURES: Adjusted odds ratio (aOR) and 95% confidence interval (CI) for the presence of specific FHR categories and characteristics. RESULTS: Category II FHR tracings were observed in 89% of women prior to delivery and were not independently associated with NE. Notably, a category III FHR was observed in 17.4% of women in the NE group compared with 0.9% of women in the control group (aOR 44.99, 95% CI 7.23-279.97). Bradycardia, minimal/absent variability, late decelerations and prolonged decelerations were independently associated with NE, whereas accelerations were protective. Similar findings were found when the cases were limited to NE with arterial cord pH <7.1 and in a subgroup analysis of women with category II tracings. CONCLUSIONS: Category III tracings, while infrequent, are not uncommon prior to delivery among fetuses who develop NE. In contrast, most FHR tracings are category II prior to delivery; however, individual FHR characteristics within this category are associated with NE. FUNDING: This research was supported by the Interdisciplinary Programme of Shanghai Jiao Tong University. TWEETABLE ABSTRACT: Category III tracings are not uncommon prior to delivery among fetuses who develop neonatal encephalopathy.

[Cerebral palsy--perinatal aspects].

Cerebral palsy is a group of non-progressive but often changing motor impairment syndromes resulting from lesions or anomalies occurring in the early stages of fetal development and childhood. This condition is responsible for significant emotional, financial and social difficulties for the patient and the family, and professionals providing specific care for these people. This review describes the incidence, risk factors and the etiopathogenesis of this condition. A lot of evidences of the relations between intrauterine infection, prematurity, prenosenost, intrapartalna asphyxia, multiple pregnancy and assisted reproductive techniques are decribed. In the review is has been demonstrated the most important aspects of perinatal cerebral palsy.

Gemelos cefalotoracópagos: diagnóstico antenatal / Cephalothoracopagus twins: antenatal diagnostic

Se describe un caso de gemelos unidos tipo cefalotoracópago diagnosticado antenatal mediante ecografía. Corresponde a una paciente de 22 años de edad, II gesta, amenorrea de 28 semanas. Control prenatal irregular, asiste a primer estudio ecográfico perinatal que reportó: embarazo gemelar, ambos en situación longitudinal, presentación podálica; con alteración de la anatomía fetal que no permite biometría, solo el fémur 4 cm. Ingresa a la institución, donde se realizó cesárea segmentaria obteniendo mortinatos pretérminos, pequeños para la edad gestacional, gemelos, cefalotoracópagos, sexo femenino. El diagnóstico se complementó con el estudio anatomopatológico confirmatorio de los diagnósticos previos.

The IUGR newborn.

Intrauterine growth restriction (IUGR) is characterized by fetal growth less than normal for the population and growth potential of a given infant. IUGR can be symmetrical with low weight, length and head circumference indicative usually of a process with its origin early in pregnancy or asymmetrical with sparing of head circumference and length due to processes occurring later in gestation. The acute neonatal consequences of IUGR are perinatal asphyxia and neonatal adaptive problems. These adaptive problems that include respiratory distress due to meconium aspiration, persistent pulmonary hypertension or pulmonary hemorrhage, abnormalities of glucose regulation, temperature instability, and polycythemia are reviewed in this article. Issues specific to the IUGR preterm infant are reviewed as well including an increased incidence of chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity and postnatal growth failure.

A loss-of-function mutation in the binding domain of HAND1 predicts hypoplasia of the human hearts.

Hypoplasia of the human heart is the most severe form of congenital heart disease (CHD) and usually lethal during early infancy. It is a leading cause of neonatal loss, especially in infants diagnosed with hypoplastic left heart syndrome (HLHS), a condition where the left side of the heart including the aorta, aortic valve, left ventricle (LV) and mitral valve are underdeveloped. The molecular causes of HLHS are unclear, but the basic helix-loop-helix (bHLH) transcription factor heart and neural crest derivatives expressed 1 (Hand1), may be a candidate culprit for this condition. The absence of Hand1 in mice resulted in the failure of rightward looping of the heart tube, a severely hypoplastic LV and outflow tract abnormalities. Nonetheless, no HAND1 mutations associated with human CHD have been reported so far. We sequenced the human HAND1 gene in heart tissues derived from 31 unrelated patients diagnosed with hypoplastic hearts. We detected in 24 of 31 hypoplastic ventricles, a common frameshift mutation (A126fs) in the bHLH domain, which is necessary for DNA binding and combinatorial interactions. The resulting mutant protein, unlike wild-type (wt) HAND1, was unable to modulate transcription of reporter constructs containing specific DNA-binding sites. Thus, in hypoplastic human hearts HAND1 function is impaired.

Customised birthweight standards accurately predict perinatal morbidity.

OBJECTIVE: Fetal growth restriction is associated with adverse perinatal outcome but is often not recognised antenatally, and low birthweight centiles based on population norms are used as a proxy instead. This study compared the association between neonatal morbidity and fetal growth status at birth as determined by customised birthweight centiles and currently used centiles based on population standards. DESIGN: Retrospective cohort study. SETTING: Referral hospital, Barcelona, Spain. PATIENTS: A cohort of 13 661 non-malformed singleton deliveries. INTERVENTIONS: Both population-based and customised standards for birth weight were applied to the study cohort. Customised weight centiles were calculated by adjusting for maternal height, booking weight, parity, ethnic origin, gestational age at delivery and fetal sex. MAIN OUTCOME MEASURES: Newborn morbidity and perinatal death. RESULTS: The association between smallness for gestational age (SGA) and perinatal morbidity was stronger when birthweight limits were customised, and resulted in an additional 4.1% (n=565) neonates being classified as SGA. Compared with non-SGA neonates, this newly identified group had an increased risk of perinatal mortality (OR 3.2; 95% CI 1.6 to 6.2), neurological morbidity (OR 3.2; 95% CI 1.7 to 6.1) and non-neurological morbidity (OR 8; 95% CI 4.8 to 13.6). CONCLUSION: Customised standards improve the prediction of adverse neonatal outcome. The association between SGA and adverse outcome is independent of the gestational age at delivery.

Whatever happened to "neonatal hepatitis"?

'Idiopathic neonatal hepatitis' is a term that has traditionally been used to denote a clinical syndrome manifest by prolonged jaundice in the neonate. This description is now used much less frequently because recent studies unite well-defined clinical, biochemical and molecular features of intrahepatic cholestasis into specific syndromes. Advances in the understanding of the molecular basis of cholestatic syndromes now enable the classification of syndromes based on biology and offer an opportunity to develop new diagnostic approaches and treatment strategies that take into account the genetic make-up of the child with cholestasis.

Fetal and neonatal ovarian cysts: what's their real meaning?

PURPOSE OF INVESTIGATION: The management of fetal ovarian cysts is still controversial despite the improvement in prenatal diagnosis with ultrasonography. Some studies suggest an aggressive management, while others opt for a conservative one. The prognosis of the majority of congenital ovarian cysts is good since they have a benign origin. Sometimes, however, complications such as torsion or rupture can occur which often require surgical intervention after delivery. In this paper we report our experience and a brief review of the literature. METHODS: The authors report on 32 pregnant women in whom ultrasonography revealed the presence of an echo-rare or echo-free area in the fetal abdomen suggestive of an ovarian cyst. All women were followed-up during pregnancy with serial ultrasound examinations. Postnatal ultrasound controls confirmed the prenatal diagnosis in all cases. The diameters of the cysts ranged from 2.7 to 7.5 cm. RESULTS: In the 16 cases (50%) in which the cyst diameter was below 4 cm, periodic ultrasound examinations revealed a tendency towards spontaneous regression of the cysts. In the other 16 cases (50%) in which the cyst diameter exceeded 4 cm, cystectomy was necessary due to subsequent complications (torsion in 6 cases, 37.5%, and intracystic hemorrhage in the other 10, 62.5%). CONCLUSION: The most appropriate clinical approach in the management of benign feto-neonatal ovarian cysts is to adopt a wait-and-see policy, assessing the course of the condition by means of periodic ultrasound monitoring. Only when tumefactions measure more than 4 cm in diameter with attendant complications is surgical therapy indicated. Without complications, however, aspiration of the cystic contents is possible even in ovarian cysts exceeding 4 cm in diameter.

Role of redox in fetal development and neonatal diseases.

In the cell, reducing and oxidizing molecules modulate the redox state. In embryonic and fetal growth, increased oxidative stress may be detrimental, but an oxidized state can also be beneficial. This is because redox may also affect key transcription factors that can alter gene expression during development. In addition, redox may impact on placentation and amniotic membrane integrity during pregnancy. Lastly, diseases of prematurity, such as necrotizing enterocolitis, retinopathy of prematurity, and chronic lung disease, may be modulated by redox in the premature. Because antioxidant therapies have not necessarily modified the outcome of these diseases, some debate exists as to this. Nonetheless, sufficient evidence suggests a role for redox throughout embryonic, fetal, and postnatal development. This evidence will be explored here.

Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase-9 levels: implications for antenatal origins of chronic lung disease.

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) degrades type IV collagen, the major constituent of lung basement membrane. We studied the effects of chorioamnionitis and antenatal corticosteroids on bronchoalveolar lavage (BAL) fluid levels of MMP-9, and its inhibitor, TIMP-1 in preterm infants. STUDY DESIGN: A prospective study was performed on serial BAL samples from 79 ventilated preterm infants at less than 33 weeks' gestation, 18 of whom were from pregnancies complicated by chorioamnionitis. MMP-9 levels were measured by gelatin zymography and TIMP-1 by enzyme-linked immunosorbent assay, and the median value for each infant was calculated. The presence and severity of chorioamnionitis were defined histologically. RESULTS: BAL fluid MMP-9 levels were higher in preterm infants in the chorioamnionitis group (86 [29-518] vs 13 [3-43] ng/mL, P =.001), and levels increased stepwise with the increasing severity of chorioamnionitis. Antenatal corticosteroids had no effect on median MMP-9 levels. Infants in the chorioamnionitis group were more likely to have chronic lung disease (CLD) develop (55% vs 28%, P <.05). TIMP-1 levels were no different between groups. CONCLUSION: Chorioamnionitis is associated with increased lung type IV collagenase levels in the ventilated preterm infant. Antenatal lung inflammation with up-regulation of MMP-9 may be important in the pathogenesis of CLD.

Maternal thyroid disease: a risk factor for newborn encephalopathy in term infants.

Two previously published studies of term newborn encephalopathy showed that maternal thyroid disease to be a risk factor. From these studies we identified 13 case and three control mothers with thyroid disease and investigated them further. The majority of affected case mothers had idiopathic or autoimmune hypothyroidism. Compared with control mothers, case mothers had fewer thyroid function tests in pregnancy, were more likely to remain on the same dose of medication throughout pregnancy and to have experienced other pregnancy complications. The association between maternal thyroid disease and encephalopathy may be the result of a series of different causal pathways, some of which are suggested by our data.

Fetal and neonatal arrhythmia in one of the twins--a case history.

There are a lot of publications about fetal arrhythmia in singletons, but up to now there are no published data about fetal arrhythmia in multiple pregnancies. In the present study a case history of fetal and neonatal arrhythmia in one of twins from two mothers treated with betamimetic agents due to imminent preterm labor is reported and discussed. A first case with fetal bradycardia due to complete A-V block had congenital cordis abnormalities (VSD and PFO). The second case with prenatal detected extrasystoles had normal heart anatomy. Digoxin was administered to the mother, in the aim to treat fetal arrhythmia without success, because the baby had postnatal bradycardia. After hospitalisation in Cardiology Department the described cases were successfully treated. In both cases the second twins were without neonatal arrhythmia and with no structural heart abnormalities. We summarise that in situation of detection fetal arrhythmia the complexity of the problems experienced may warrant early referral to a tertiary centre where the overall management of the mother, fetus and neonate, may be undertaken.

Neonatal morbidity and mortality secondary to premature rupture of membranes.

PROM is one of the most common complications of pregnancy that has a major impact on neonatal mortality and morbidity. The occurrence of PROM is either directly or indirectly responsible for a large number of premature births and the concomitant mortality and morbidity associated with preterm delivery. PROM turns a pregnancy into a high-risk situation and increases the need for neonatal resuscitation in the delivery room. The incidence of neonatal sepsis increases with PROM, but the overall outcome of the neonate, even with surfactant therapy, is still primarily dependent on the gestational age at the time of delivery. This is most relevant between 24 and 27 weeks' gestation. During this 3-week interval, survival improves by almost 2% for each additional day of in utero maturation (i.e., from 35 to 75%). Thus the benefit to the fetus of prolonging the pregnancy in cases of PROM is immensely worthwhile and should be aggressively pursued as long as there is no significant increase in maternal morbidity.

The legal concept of wrongful life.

KIE: "Wrongful birth" suits are malpractice actions in which parents sue a physician for negligent conduct resulting in the birth of an impaired child. "Wrongful life" suits, which are more controversial, are brought on behalf of the impaired infant rather than the parents. Thus, the physician is sued, not for causing the impairment, but for negligent responsibility for the infant's very existence. After tracing the history of wrongful life cases in the U.S., Botkin analyzes the fundamental problems in the wrongful life concept in terms of the physician's alleged duty to the fetus and in terms of the concept of life as a harm. He urges rejection of this relatively new cause of action that threatens the judicial system's traditional respect for the intrinsic value of life.^ieng

Obstetrical-neonatal neurological relationship. A replication study.

A study concerning the relationship between neonatal neurological abnormality and 3 parameters of pre- and perinatal condition in a birth cohort of 1507 infants was replicated in a second cohort of 1655 infants. The 3 parameters chosen were preterm birth, intrauterine growth retardation and neonatal acidemia. The neurological examination in the second cohort was carried out by other examiners than in the first cohort. The incidence of neurological abnormality was again found to be raised in all 3 categories and again least in the acidemic subgroup. Also the finding could be confirmed that only in about half of the neurologically abnormal infants could the 3 parameters have exerted any effect at all, which implies the necessity of further analysis. This replication study shows that neurological examination in the newborn period is a reliable tool for the evaluation of the condition of infants with respect to their pre- and perinatal history.