Early relationship between very preterm infant and mother: The role of infant, maternal and dyadic factors

Pienipainoisen keskosen ja äidin varhainen suhde: Lapsen, äidin ja dyadisten muuttujien vaikutus Tämän tutkimuksen tavoitteena oli tutkia keskosvauvan ja äidin varhaista suhdetta. Tutkimuksessa selvitettiin myös vauvan itkukäyttäytymisen, vauvan sylissä olon ja äidin masentuneisuuden yhteyttä äidin ja keskosvauvan varhaiseen suhteeseen. Tutkimusryhmät koostuivat 32:sta (tutkimus I-II) ja 38:sta (tutkimus III-IV) keskosena syntyneestä vauvasta (syntymäpaino < 1501 g tai GI < 32 viikkoa) sekä 46:sta täysiaikaisena syntyneestä terveestä verrokkivauvasta. Lapsen ja äidin vuorovaikutusta arvioitiin 6 ja 12 kuukauden iässä (korjattu ikä) PCERAmenetelmällä. Äidin mielikuvia lapsestaan tutkittiin WMCI-haastattelulla, kun lapsi oli 12 kuukautta. Baby Day Diary -menetelmää käytettiin vauvan itkukäyttäytymisen ja sylissä olon keston mittaamisessa vauvan ollessa 5 kuukautta. Äidin masentuneisuutta arvioitiin EDPS-lomakkeella, kun lapsi oli 6 kuukautta. Tulokset osoittivat, että turvallisten kiintymyssuhdemielikuvien määrä tai vuorovaikutuksen laatu eivät keskosvauvan äideillä eronneet täysiaikaisina syntyneiden vauvojen äitien vastaavista. Ryhmien välillä ei löytynyt eroja myöskään dyadisen vuorovaikutuksen laadussa. Keskosena syntyneet lapset olivat kuitenkin vetäytyvämpiä ja heillä oli laadullisesti heikommat keskittymisen ja leikin taidot vuorovaikutustilanteessa 12 kuukauden iässä täysiaikaisina syntyneisiin lapsiin nähden. Lisäksi äidin masentuneisuus ja lapsen pitkittynyt itkuisuus olivat negatiivisessa yhteydessä vuorovaikutuksen laatuun keskosvauvojen ryhmässä. Vauvan itkukertojen määrän, sylissä olon keston sekä äidin ja vauvan vuorovaikutuksen laadun välillä löytyi positiivinen yhteys ainoastaan keskosena syntyneiden lasten ryhmässä. Tulostemme perusteelle toteamme, että lapsen ennenaikainen syntymä itsessään ei näytä muodostavan riskiä äidin vuorovaikutuksen laadulle tai turvalliselle kiintymyssuhteelle. Yhdessä muiden riskitekijöiden kanssa keskosuus kuitenkin altistaa vauvat ja heidän äitinsä varhaisen vuorovaikutuksen ongelmille. Lisäksi tuloksemme viittaavat siihen, että vauvan itku ja siitä seuraava sylissä olo toimivat suojaavana mekanismina pienipainoisen keskosen ja äidin varhaisessa suhteessa.

Human papillomavirus (HPV) in mothers before and after delivery – a three year follow-up study.

Human papillomavirus (HPV) infections in mothers are important to consider since pregnancy may affect the outcome of the infection and the mother may transmit HPV to the child. This thesis is part of the 3-year Finnish Family HPV Study on HPV infection dynamics within 329 families. The presence of maternal HPV antibodies and HPV DNA in placenta, umbilical cord blood and breast milk was examined. In addition, genital and oral HR-HPV carriage was studied among mothers with one or two pregnancies. At enrollment, seropositivity to HPV 6, 11, 16, 18 and 45 was recorded in 53 %, 21 %, 35 %, 21 % and 9 % of the mothers, respectively. Age at sexual debut, number of sexual partners, a history of genital warts and antibodies to LR/HR-HPV predicted HR/LR-HPV-seropositivity. During follow-up 27 %, 14 %, 17 %, 17 % and 7 % of the mothers seroconverted to the tested HPV-types, respectively. Decay of HPV-antibodies was rare. The mother’s new pregnancy was of minor impact in the outcome of oral and cervical HR-HPV infections. HPV-DNA was present in 4.2 % and 3.5 % of the placentas and umbilical cord blood samples, and in 4.5 % and 19.7 % of the breast milk samples collected at day 3 and month 2 postpartum, respectively. HPV-positivity in placenta/cord blood was related to a history of abnormal pap-smears or genital warts, and raised the risk of the neonate being HPV-positive at birth. The mode of delivery did not predict the HPVstatus of neonate, placenta, or cord blood. HPV DNA in breast milk was associated with oral HPV status of the father, but not with HPV status of the neonate. The results indicate that exposure to HPV is common and that part of the exposure might take place already early in life. Contrary to the common claim, pregnancy is not a risk factor for HPV.

Probiotic interventions in infancy: Benefit and Safety Assessment of Extended Applications

Immaturity of the gut barrier system in the newborn has been seen to underlie a number of chronic diseases originating in infancy and manifesting later in life. The gut microbiota and breast milk provide the most important maturing signals for the gut-related immune system and reinforcement of the gut mucosal barrier function. Recently, the composition of the gut microbiota has been proposed to be instrumental in control of host body weight and metabolism as well as the inflammatory state characterizing overweight and obesity. On this basis, inflammatory Western lifestyle diseases, including overweight development, may represent a potential target for probiotic interventions beyond the well documented clinical applications. The purpose of the present undertaking was to study the efficacy and safety of perinatal probiotic intervention. The material comprised two ongoing, prospective, double-blind NAMI (Nutrition, Allergy, Mucosal immunology and Intestinal microbiota) probiotic interventions. In the mother-infant nutrition and probiotic study altogether 256 women were randomized at their first trimester of pregnancy into a dietary intervention and a control group. The intervention group received intensive dietary counselling provided by a nutritionist, and were further randomized at baseline, double-blind, to receive probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis) or placebo. The intervention period extended from the first trimester of pregnancy to the end of exclusive breastfeeding. In the allergy prevention study altogether 159 women were randomized, double-blind, to receive probiotics (Lactobacillus rhamnosus GG) or placebo 4 weeks before expected delivery, the intervention extending for 6 months postnatally. Additionally, patient data on all premature infants with very low birth weight (VLBW) treated in the Department of Paediatrics, Turku University Hospital, during the years 1997 - 2008 were utilized. The perinatal probiotic intervention reduced the risk of gestational diabetes mellitus (GDM) in the mothers and perinatal dietary counselling reduced that of fetal overgrowth in GDM-affected pregnancies. Early gut microbiota modulation with probiotics modified the growth pattern of the child by restraining excessive weight gain during the first years of life. The colostrum adiponectin concentration was demonstrated to be dependent on maternal diet and nutritional status during pregnancy. It was also higher in the colostrum received by normal-weight compared to overweight children at the age of 10 years. The early perinatal probiotic intervention and the postnatal probiotic intervention in VLBW infants were shown to be safe. To conclude, the findings in this study provided clinical evidence supporting the involvement of the initial microbial and nutritional environment in metabolic programming of the child. The manipulation of early gut microbial communities with probiotics might offer an applicable strategy to impact individual energy homeostasis and thus to prevent excessive body-weight gain. The results add weight to the hypothesis that interventions aiming to prevent obesity and its metabolic consequences later in life should be initiated as early as during the perinatal period.

Nuorena vanhemmaksi tulemista ja raskaudenkeskeytystä ennustavat lapsuusiän tekijät

Tämän tutkimuksen tavoitteena oli tutkia kahdeksan vuoden iässä arvioitujen perhetekijöiden, psyykkisten oireiden ja kiusaamiskäyttäytymisen yhteyttä äidiksi tulemiseen alle 20-vuotiaana, isäksi tulemiseen alle 22-vuotiaana ja raskaudenkeskeytyksen tekemiseen alle 29-vuotiaana. Tutkimus perustui suomalaiseen LAPSET-kohorttiin, joka on yleisväestöotos (n=5813) vuonna 1981 syntyneistä henkilöistä. Vuonna 1989 tutkittavat sekä heidän vanhempansa ja opettajansa vastasivat psyykkistä oireilua ja kiusaamista koskeviin kyselyihin. Vanhemmat antoivat tietoa myös perhetekijöistä ja opettajat koulumenestyksestä. Tiedot tyttöjen (n=2694, 94 % osallistuneista tytöistä) synnytyksistä ja raskaudenkeskeytyksistä kerättiin hoitoilmoitusrekisteristä ja raskaudenkeskeyttämisrekisteristä. Poikien (n=2721, 92 % osallistuneista pojista) osalta nuorena isäksi tuleminen selvitettiin väestötietojärjestelmästä. Nuorten äitien tyttäret tulivat vanhempien äitien tyttäriä todennäköisemmin nuorena äidiksi ja nuorten isien pojat nuorena isäksi. Matalasti koulutettujen äitien pojilla oli kohonnut todennäköisyys nuorena isäksi tulemiseen ja tyttärillä raskaudenkeskeytykseen. Muu kuin kahden biologisen vanhemman muodostama perherakenne oli yhteydessä nuorena äidiksi tulemiseen ja raskaudenkeskeytykseen. Lapsuuden käytösongelmat olivat yhteydessä nuorena vanhemmaksi tulemiseen sekä raskaudenkeskeytykseen. Ylivilkkaus oli yhteydessä nuorena äidiksi tulemiseen. Tytöistä ne, jotka olivat kiusaajia tai kiusaaja-kiusattuja, tulivat todennäköisimmin nuorena äidiksi ja pojista kiusaaja-kiusatut nuorena isäksi. Kiusaaminen ei ollut yhteydessä raskaudenkeskeytyksen tekemiseen. Tutkimustuloksia voidaan hyödyntää terveydenhuollossa kohdattaessa nuoria vanhempia ja muita nuoria. Lisäksi niillä voi olla merkitystä esimerkiksi suunniteltaessa toimenpiteitä, joiden tavoitteena on nuorten epätoivottujen raskauksien ehkäiseminen.

The effects of maternal hyperglycemia on human umbilical vascular gene expression and neonatal rat lung development

Background: Maternal diabetes affects many fetal organ systems, including the vasculature and the lungs. The offspring of diabetic mothers have respiratory adaptation problems after birth. The mechanisms are multifactorial and the effects are prolonged during the postnatal period. An increasing incidence of diabetic pregnancies accentuates the importance of identifying the pathological mechanisms, which cause the metabolic and genetic changes that occur in offspring, born to diabetic mothers. Aims and methods: The aim of this thesis was to determine changes both in human umbilical cord exposed to maternal type 1 diabetes and in neonatal rat lungs after streptozotocin-induced maternal hyperglycemia, during pregnancy. Rat lungs were used as a model for the potential disease mechanisms. Gene expression alterations were determined in human umbilical cords at birth and in rat pup lungs at two week of age. During the first two postnatal weeks, rat lung development was studied morphologically and histologically. Further, the effect of postnatal hyperoxia on hyperglycemia-primed rat lungs was investigated at one week of age to mimic the clinical situation of supplemental oxygen treatment. Results: In the umbilical cord, maternal diabetes had a major negative effect on the expression of genes involved in blood vessel development. The genes regulating vascular tone were also affected. In neonatal rat lungs, intrauterine hyperglycemia had a prolonged effect on gene expression during late alveolarization. The most affected pathway was the upregulation of extracellular matrix proteins. Newborn rat lungs exposed to intrauterine hyperglycemia had thinner saccular walls without changes in airspace size, a smaller relative lung weight and lung total tissue area, and increased cellular apoptosis and proliferation compared to control lungs, possibly reflecting an aberrant maturational adaptation. At one and two weeks of age, cell proliferation and secondary crest formation were accelerated in hyperglycemia-exposed lungs. Postnatal hyperoxic exposure, alone caused arrested alveolarization with thin-walled and enlarged alveoli. In contrast, the dual exposure of intrauterine hyperglycemia and postnatal hyperoxia resulted in the phenotype of thick septa together with arrested alveolarization and decreased number of small pulmonary arteries. Conclusions: Maternal diabetic environment seems to alter the umbilical cord gene expression profile of the regulation of vascular development and function. Fetal hyperglycemia may additionally affect the genetic regulation of the postnatal lung development and may actually induce prolonged structural alterations in neonatal lungs together with a modifying effect on the deleterious pulmonary exposure of postnatal hyperoxia. This, combined with the novel human umbilical cord gene data could serve as stepping stones for future therapies to curb developmental aberrations.

Cesarean section - short term maternal complications related to the mode of delivery

Cesarean section (CS) is the most common major surgery performed on women worldwide. CS can save the life of the mother or the fetus, but is associated with the typical complications of any major surgery: hemorrhage, infection, venous thromboembolism and complications of anesthesia, sometimes leading to maternal death. Recently there have been several reports from well resourced countries on increased severe maternal morbidity and even mortality. Increased rates of CS, obesity and older mothers may explain this rise. The aim of this thesis is to study the rates and risk factors of short term maternal complications associated with CS. Also, we compared maternal morbidity by mode of delivery and over time. The complication rates were assessed in a prospective study involving 2496 CS performed in the 12 largest delivery units in Finland in 2005. The rates of severe complications were studied by mode of delivery in a register-based study comparing national cohorts in 1997 and 2002. The impact of several risk factors on severe maternal morbidity by mode of delivery was studied in a register-based study of all singleton deliveries in 2007-2011. In the prospective study, 27% of the women who underwent CS had one or more intraoperative or postoperative complications during their hospital stay, and 10% had a severe complication. In the register-based study the incidence of life-threatening maternal complications was 7.6 in 1000 deliveries. The incidence was lowest for vaginal delivery (VD), followed by instrumental VD and elective CS, and highest in emergency CS. An attempt of VD, including the risks associated with emergency CS, seems to be the safest mode of delivery, even for most high-risk women.

”Päihdeäidit” hyvinvointivaltion huomassa : kurinpitoa ja suostuttelua

Kirjallisuusarvostelu

Biomarkers, medical treatment and fetal intrapartum surveillance in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterized by maternal pruritus and elevated liver enzymes. It usually begins in the third trimester of pregnancy and resolves spontaneously after delivery. ICP is considered benign for the pregnant woman, but it is associated with an increased risk for unexplained term stillbirth and preterm delivery. There are no specific laboratory markers to diagnose ICP. The diagnosis is currently based on the presence of maternal pruritus and elevated values of alanine aminotransaminases (ALT) and serum bile acids (BA). Recently, ursodeoxycholic acid (UDCA) has been used for treatment. Mechanisms leading to intrauterine fetal death (IUFD) may be multifactorial and are unknown at present. For this thesis, 415 pregnant women with ICP were studied. The aim was to evaluate the value of the liver enzyme glutathione S-transferase alpha (GSTA) as a specific marker of ICP and to assess the effect of maternal UDCA therapy on maternal laboratory values and fetal outcome. The specific markers predisposing the fetus to heart arrhythmia were studied by comparing waveform analysis of fetal electrocardiograms (FECG) during labor in pregnancies complicated by ICP with controls. The levels of maternal GSTA were high and the values correlated with the value of ALT in patients with ICP. UDCA therapy reduced the values of the liver enzymes and alleviated maternal pruritus, but it did not influence maternal hormonal values. Although the newborns experienced an uneventful perinatal outcome, severe ICP was still associated with preterm birth and admission to the neonatal intensive care unit (NICU). There were no significant differences in intrapartum FECG findings between fetuses born to ICP women and controls.

The viability of a tool for fetal health monitoring

Health monitoring has become widespread these past few years. Such applications include from exercise, food intake and weight watching, to specific scenarios like monitoring people who suffer from chronic diseases. More and more we see the need to also monitor the health of new-born babies and even fetuses. Congenital Heart Defects (CHDs) are the main cause of deaths among babies and doctors do not know most of these defects. Hence, there is a need to study what causes these anomalies, and by monitoring the fetus daily there will be a better chance of identifying the defects in earlier stages. By analyzing the data collected, doctors can find patterns and come up with solutions, thus saving peoples’ lives. In many countries, the most common fetal monitor is the ultrasound and the use of it is regulated. In Sweden for normal pregnancies, there is only one ultrasound scan during the pregnancy period. There is no great evidence that ultrasound can harm the fetus, but many doctors suggest to use it as little as possible. Therefore, there is a demand for a new non-ultrasound device that can be as accurate, or even better, on detecting the FHR and not harming the baby. The problems that are discussed in this thesis include how can accurate fetus health be monitored non-invasively at home and how could a fetus health monitoring system for home use be designed. The first part of the research investigates different technologies that are currently being used on fetal monitoring, and techniques and parameters to monitor the fetus. The second part is a qualitative study held in Sweden between April and May 2016. The data for the qualitative study was collected through interviews with 21 people, 10 mothers/mothers-to-be and 11 obstetricians/gynecologists/midwives. The questions were related to the Swedish pregnancy protocol, the use of technology in medicine and in particular during the pregnancy process, and the use of an ECG based monitoring device. The results show that there is still room for improvements on the algorithms to extract the fetal ECG and the survey was very helpful in understanding the need for a fetal home monitor. Parents are open to new technologies especially if it doesn't affect the baby's growth. Doctors are open to use ECG as a great alternative to ultrasound; on the other hand, midwives are happy with the current system. The remote monitoring feature is very desirable to everyone, if such system will be used in the future.